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Aberystwyth University
1.
Finch, Jasen.
Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae.
Degree: PhD, 2016, Aberystwyth University
URL: http://hdl.handle.net/2160/43c47b4f-9bc5-449d-af3d-2f1dce53949e 
► Fungal biotrophic phytopathogens such as Magnaporthe oryzae, the causal agent of rice blast disease, are becoming increasingly important in crop losses worldwide with the onset…
(more)
▼ Fungal biotrophic phytopathogens such as Magnaporthe oryzae, the causal agent of rice blast disease, are becoming increasingly important in crop losses worldwide with the onset of anthropogenic climate change and monoculture farming practices. The use of model organisms such as the grass species Brachypodium distachyon provides the opportunity undertake large-scale integrated omics analyses that would otherwise be infeasible. These can provide insights into the system-wide responses of plants to pathogen infection as well as identify areas of the host plant system that could be targets for pathogen manipulation. A spectral binning method for high resolution metabolome ngerprinting was developed along with the R package binneR as a software implementation for routine application of the method. This was applied to investigate experimental control and robustness in plant-pathogen interactions, with the development of a new inoculation strategy for appropriately controlling inoculum derived responses unrelated to M. oryzae pathogenesis. Large-scale, high resolution metabolomic ngerprinting and proling, along with RNA-Seq transcriptomic analyses, were conducted for the interaction between B. distachyon and M. oryzae and identifed dynamic changes during the pre-symptomatic biotrophic phases. Both data and knowledge driven omics integration strategies identied associations between the transcriptomic and metabolomic changes during the interaction, with chloroplasts and nitrogen metabolism found as key response areas. A disease resistance locus Rbr1 was identied using QTL analyses on chromosome 4 of B. distachyon for resistance to M. oryzae utilising computer vision based phenotyping. Eight candidate NB-LRR resistance genes were found within this locus.
Subjects/Keywords: 572
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APA (6th Edition):
Finch, J. (2016). Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae. (Doctoral Dissertation). Aberystwyth University. Retrieved from http://hdl.handle.net/2160/43c47b4f-9bc5-449d-af3d-2f1dce53949e
Chicago Manual of Style (16th Edition):
Finch, Jasen. “Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae.” 2016. Doctoral Dissertation, Aberystwyth University. Accessed March 04, 2021.
http://hdl.handle.net/2160/43c47b4f-9bc5-449d-af3d-2f1dce53949e.
MLA Handbook (7th Edition):
Finch, Jasen. “Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae.” 2016. Web. 04 Mar 2021.
Vancouver:
Finch J. Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae. [Internet] [Doctoral dissertation]. Aberystwyth University; 2016. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/2160/43c47b4f-9bc5-449d-af3d-2f1dce53949e.
Council of Science Editors:
Finch J. Integrated omics analyses of the interaction between Brachypodium distachyon and Magnaprthe oryzae. [Doctoral Dissertation]. Aberystwyth University; 2016. Available from: http://hdl.handle.net/2160/43c47b4f-9bc5-449d-af3d-2f1dce53949e
2.
Price, Claire Louise.
Candida CYP52 : alkane and fatty acid metabolism.
Degree: PhD, 2012, Swansea University
URL: https://cronfa.swan.ac.uk/Record/cronfa42696
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752286
► Cytochromes P450 are a superfamily of haem-thiolate proteins found in all kingdoms of life. To date 11294 enzymes have been identified and have been shown…
(more)
▼ Cytochromes P450 are a superfamily of haem-thiolate proteins found in all kingdoms of life. To date 11294 enzymes have been identified and have been shown to be involved in the metabolism of a wide variety of substrates, including hydrocarbons and xenobiotics. In yeast and fungi the hydroxylation of alkanes is associated with a family of cytochromes P450 enzymes known as CYP52s. These enzymes are involved in the terminal hydroxylation of long-chain alkanes resulting in the production of alcohols, which can be further converted to form fatty acids and diacids. In vivo such hydrocarbons can be subjected to beta-oxidation for use in growth. Alternatively, the products formed by CYP52 catalysed hydroxylation in vitro can be used in biotechnological applications. They can be used as platform chemicals in the production of a number of industrial products, including plastics, fragrances and antibiotics. The p-oxidation of fatty acids has been less well documented for Candida albicans than for other Candida species, therefore it was the aim of this study to investigate a) did cytochromes P450 exist in C. albicans that could possibly fulfil this function and b) to definitively assign function to a single cytochrome P450. Using a bioinformatic approach, five putative CYP52s were identified in C. albicans. Of these CYP52s, Alk1 was shown to have the greatest homology to the archetypal alkane-assimilating CYP52, CYP52A3 from C. maltosa. ALK1 heterologous gene expression in the brewer's yeast Saccharomyces cerevisiae allowed growth on hexadecane (C16:0) as the sole carbon source. This showed for the first time that Alk1 is involved in the hydroxylation of long-chain alkanes as normally S. cerevisiae is unable to utilise alkanes for growth. This study has also shown that Alk1 is able to interact with sterol substrates suggesting a possible role for CYP52s in sterol metabolism, which was previously unknown.
Subjects/Keywords: 572
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APA (6th Edition):
Price, C. L. (2012). Candida CYP52 : alkane and fatty acid metabolism. (Doctoral Dissertation). Swansea University. Retrieved from https://cronfa.swan.ac.uk/Record/cronfa42696 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752286
Chicago Manual of Style (16th Edition):
Price, Claire Louise. “Candida CYP52 : alkane and fatty acid metabolism.” 2012. Doctoral Dissertation, Swansea University. Accessed March 04, 2021.
https://cronfa.swan.ac.uk/Record/cronfa42696 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752286.
MLA Handbook (7th Edition):
Price, Claire Louise. “Candida CYP52 : alkane and fatty acid metabolism.” 2012. Web. 04 Mar 2021.
Vancouver:
Price CL. Candida CYP52 : alkane and fatty acid metabolism. [Internet] [Doctoral dissertation]. Swansea University; 2012. [cited 2021 Mar 04].
Available from: https://cronfa.swan.ac.uk/Record/cronfa42696 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752286.
Council of Science Editors:
Price CL. Candida CYP52 : alkane and fatty acid metabolism. [Doctoral Dissertation]. Swansea University; 2012. Available from: https://cronfa.swan.ac.uk/Record/cronfa42696 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752286
3.
Hitchings, Matthew D.
Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins.
Degree: PhD, 2013, Swansea University
URL: https://cronfa.swan.ac.uk/Record/cronfa42992
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752307
► The three DNA protection proteins from starved cells (Dps) of Streptomyces coelicolor are members of the min-ferritin super family. Considered to be of major importance…
(more)
▼ The three DNA protection proteins from starved cells (Dps) of Streptomyces coelicolor are members of the min-ferritin super family. Considered to be of major importance to stress response systems in microorganisms. Dps proteins can aid microbial survival in extreme conditions. The S. coelicolor Dps proteins are not only induced in response to stress in a stimulus-dependent manner, but dual regulation allows these proteins to play a role in bacterial cell division; influencing condensation of nucleoids during spore formation. This study investigates the structural and functional properties of the ScDps proteins and finds multiple ways in which the homologs differ.
Subjects/Keywords: 572
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APA (6th Edition):
Hitchings, M. D. (2013). Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins. (Doctoral Dissertation). Swansea University. Retrieved from https://cronfa.swan.ac.uk/Record/cronfa42992 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752307
Chicago Manual of Style (16th Edition):
Hitchings, Matthew D. “Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins.” 2013. Doctoral Dissertation, Swansea University. Accessed March 04, 2021.
https://cronfa.swan.ac.uk/Record/cronfa42992 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752307.
MLA Handbook (7th Edition):
Hitchings, Matthew D. “Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins.” 2013. Web. 04 Mar 2021.
Vancouver:
Hitchings MD. Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins. [Internet] [Doctoral dissertation]. Swansea University; 2013. [cited 2021 Mar 04].
Available from: https://cronfa.swan.ac.uk/Record/cronfa42992 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752307.
Council of Science Editors:
Hitchings MD. Biochemical and structural analysis of the Streptomyces coelicolor Dps proteins. [Doctoral Dissertation]. Swansea University; 2013. Available from: https://cronfa.swan.ac.uk/Record/cronfa42992 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.752307
4.
Mbouamboua, Yvon.
Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host.
Degree: Docteur es, Génomique et Bioinformatique, 2019, Aix-Marseille; Université Marien-Ngouabi (Brazzaville). Faculté des sciences
URL: http://www.theses.fr/2019AIXM0332
► J’ai travaillé premièrement sur la caractérisation moléculaire des infections submicroscopiques à Plasmodium falciparum chez les femmes enceintes à Brazzaville. Dans les zones d’endémie palustre, la…
(more)
▼ J’ai travaillé premièrement sur la caractérisation moléculaire des infections submicroscopiques à Plasmodium falciparum chez les femmes enceintes à Brazzaville. Dans les zones d’endémie palustre, la plupart des femmes enceintes sont susceptibles aux infections asymptomatiques à P. falciparum. Malgré la mise en place du traitement préventif intermittent à base de la sulfadoxine-pyriméthamine (TPI-SP), l’infection placentaire persiste et n’est pas maîtrisée. Dans le but de comprendre les causes de cette persistance, j’ai caractérisé les parasites de P. falciparum chez les femmes enceintes Congolaises sous TPI-SP et j’ai analysé leurs profils génétiques dans le sang périphérique, placentaire et du cordon ombilical. L’évaluation de la fréquence de l’infection plasmodiale a montré qu’il y’a une baisse de la fréquence des infections microscopiques chez les femmes sous TPI et une augmentation de la fréquence des infections submicroscopiques avec une diversité génétique modérée. Ces résultats contribuent à la compréhension de la dynamique de la population parasitaire en circulation au Congo.Deuxièmement j’ai développé une méthode bioinformatique de prédiction des variants régulateurs des régions non-codantes associés à des maladies. L’approche repose sur l’intégration d’éléments d’informations collectées automatiquement à partir des bases de données Ensembl, dbSNP et GWAS catalog, et sur la sélection des variations susceptibles d’affecter la régulation, en combinant des outils bioinformatiques spécialisés : analyse de motifs (Regulatory Sequence Analysis Tools) et de données ChIP-seq (ReMap).
I first worked on the molecular characterization of submicroscopic Plasmodium falciparum infections in pregnant women in Brazzaville. In malaria-endemic areas, most pregnant women are susceptible to asymptomatic P. falciparum infections. Despite the implementation of intermittent preventive treatment with sulfadoxine-pyrimethamine (TPI-SP), placental infection persists and is not controlled. In order to understand the causes of this persistence, I characterized parasites of P. falciparum in Congolese pregnant women on TPI-SP and analyzed their genetic profiles in peripheral, placental and umbilical cord blood. The evaluation of the frequency of the plasmodial infection has shown that there is a decrease in the frequency of microscopic infections in women on IPT and an increase in the frequency of submicroscopic infections with moderate genetic diversity. These results contribute to the understanding of the dynamics of the parasitic population circulating in Congo.Second, I developed a bioinformatic method for predicting regulatory variants of noncoding regions associated with diseases. The approach is based on the integration of information elements collected automatically from the Ensembl, dbSNP and GWAS catalogs, and on the selection of variations that may affect regulation, by combining specialized bioinformatics tools: analysis Regulatory Sequence Analysis Tools and ChIP-seq (ReMap) data.
Advisors/Committee Members: Van Helden, Jacques (thesis director), Ntoumi, Francine (thesis director).
Subjects/Keywords: .; .; 572
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APA (6th Edition):
Mbouamboua, Y. (2019). Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host. (Doctoral Dissertation). Aix-Marseille; Université Marien-Ngouabi (Brazzaville). Faculté des sciences. Retrieved from http://www.theses.fr/2019AIXM0332
Chicago Manual of Style (16th Edition):
Mbouamboua, Yvon. “Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host.” 2019. Doctoral Dissertation, Aix-Marseille; Université Marien-Ngouabi (Brazzaville). Faculté des sciences. Accessed March 04, 2021.
http://www.theses.fr/2019AIXM0332.
MLA Handbook (7th Edition):
Mbouamboua, Yvon. “Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host.” 2019. Web. 04 Mar 2021.
Vancouver:
Mbouamboua Y. Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host. [Internet] [Doctoral dissertation]. Aix-Marseille; Université Marien-Ngouabi (Brazzaville). Faculté des sciences; 2019. [cited 2021 Mar 04].
Available from: http://www.theses.fr/2019AIXM0332.
Council of Science Editors:
Mbouamboua Y. Combinaison d'approches expérimentales et bioinformatiques pour caractériser les interactions entre Plasmodium falciparum et son hôte humain : Combination of experimental and bioinformatic approaches to characterize the interactions between Plasmodium falciparum and its human host. [Doctoral Dissertation]. Aix-Marseille; Université Marien-Ngouabi (Brazzaville). Faculté des sciences; 2019. Available from: http://www.theses.fr/2019AIXM0332
5.
España, Alexandre.
Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia.
Degree: Docteur es, Génomique et Bioinformatique, 2019, Aix Marseille Université
URL: http://www.theses.fr/2019AIXM0481
► Un certain nombre d'anomalies génétiques dans la leucémie aiguë lymphoblastique de type T (LAL-T) touche généralement des facteurs de transcription ou des régulateurs épigénétiques et…
(more)
▼ Un certain nombre d'anomalies génétiques dans la leucémie aiguë lymphoblastique de type T (LAL-T) touche généralement des facteurs de transcription ou des régulateurs épigénétiques et ont principalement pour effet de bloquer la différenciation des lymphocytes T, délimitant ainsi des sous-groupes de LAL-T avec des profils d'expression génétique spécifiques. La régulation de l’expression des gènes spécifiques d’un type cellulaire nécessite l’interaction de différents types d’éléments cis-régulateurs (promoteurs, amplificateurs/enhancers, isolateurs, inactivateurs. Etant donné le rôle bien reconnu de la dérégulation épigénétique dans la leucémogenèse, il est probable qu’une fraction importante des enhancers oncogéniques reste à découvrir et à évaluer sur le plan fonctionnel, et ce fût l'objet de mon travail de thèse. Nous avons identifié des enhancers potentiels dans des sous-populations de cellules du thymus sain et dans des cellules tumorales de patients atteints de LAL-T et ainsi déterminé 17406 enhancers potentiels dérégulés dans la LAL-T. Parmi eux se trouvent des enhancers proches d’une liste de gènes connus pour être altérés dans la LAL-T et des enhancers dont la présence est corrélée avec la surexpression d’oncogènes proches (NKX3-1, NKX3-2, TAL1, MYC, LMO2, ou JDP2). Nous avons également identifié un nouvel enhancer de TAL1 apparu à la suite d’une mutation somatique monoallélique incorporant un site MYB. Nous avons également mis en place deux stratégies de criblage haut-débit pour évaluer l’activité et la fonction des potentiels enhancers, et valider par une approche de CRISPR/Cas9 la pertinence oncogénique de l'enhancer de NKX3-2 et du gène HHEX.
Several genetic abnormalities in T-cell acute lymphoblastic leukemia (T-ALL) affect transcription factors or epigenetic regulators and mainly block the differentiation of T cells, thus delimiting subgroups of AL-T with specific genetic expression profiles. The regulation of the expression of cell-type-specific genes requires the interaction of different types of cis-regulatory elements (promoters, enhancers, isolators, inactivators. Given the well-recognized role of epigenetic deregulation in leukemogenesis, it is likely that a significant fraction of oncogenic enhancers remains to be discovered and functionally evaluated, and this was the subject of my thesis work. We identified potential enhancers in subpopulations of healthy thymus cells and tumor cells of LAL-T patients and thus determined 17,406 potential enhancers deregulated in T-ALL. Enhancers close to a list of genes known to be altered in LAL-T and enhancers whose presence is correlated with the overexpression of close oncogenes (NKX3-1, NKX3-2, TAL1, MYC, LMO2, or JDP2) are among them. We have also identified a new enhancer of TAL1 that appeared following a monoallelic somatic mutation incorporating a MYB site. Additionally, two high-throughput screening strategies (CapSTARR-seq and CRISPRi) have been implemented to evaluate the activity and function of potential enhancers, as well as validate the…
Advisors/Committee Members: Spicuglia, Salvatore (thesis director), Pradel, Lydie (thesis director).
Subjects/Keywords: .; .; 572
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APA ·
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CSE |
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Manager
APA (6th Edition):
España, A. (2019). Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2019AIXM0481
Chicago Manual of Style (16th Edition):
España, Alexandre. “Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia.” 2019. Doctoral Dissertation, Aix Marseille Université. Accessed March 04, 2021.
http://www.theses.fr/2019AIXM0481.
MLA Handbook (7th Edition):
España, Alexandre. “Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia.” 2019. Web. 04 Mar 2021.
Vancouver:
España A. Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia. [Internet] [Doctoral dissertation]. Aix Marseille Université 2019. [cited 2021 Mar 04].
Available from: http://www.theses.fr/2019AIXM0481.
Council of Science Editors:
España A. Caractérisation des enhancers dérégulés dans la leucémie aiguë lymphoblastique de type T : Characterization of deregulated enhancers in T-cell acute lymphoblastic leukemia. [Doctoral Dissertation]. Aix Marseille Université 2019. Available from: http://www.theses.fr/2019AIXM0481
University of Oxford
6.
Shen, Xin.
Characterising the rhomboid-like protein TMEM115.
Degree: PhD, 2017, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:171e08c3-15f1-4d09-ba59-01b2007f140c
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740827
► The rhomboid-like superfamily of proteins comprises transmembrane proteins with an ancient evolutionary origin. They include both intramembrane serine proteases and inactive pseudoproteases, and they have…
(more)
▼ The rhomboid-like superfamily of proteins comprises transmembrane proteins with an ancient evolutionary origin. They include both intramembrane serine proteases and inactive pseudoproteases, and they have diverse cellular and pathophysiological functions. These include regulation of growth factor signalling, protein quality control, trafficking, and mitochondrial dynamics. TMEM115, a recently recognised enzymatically inactive member of the rhomboid-like superfamily (confirmed in this thesis), is conserved from yeast to human and is ubiquitously expressed in all tissues. The absence of TMEM115 in both Drosophila and mice causes severe phenotypes. These compelling preliminary data indicate that TMEM115 has important cellular functions. To capitalise on these preliminary observations, the overall aim of my PhD project was to characterise the mammalian TMEM115 both structurally and functionally. Structurally, I performed a topology study for TMEM115, and with a combination of bioinformatic and experimental analysis, proved that TMEM115 indeed has a six TMD structure. Using the HHpred and Phyre algorithms, which identify structural similarity among proteins, a high degree of homology was identified between the TMD regions of TMEM115 and other rhomboid-like proteins. The above analysis together with the topology of TMEM115 definitively positions TMEM115 in the rhomboid-like superfamily. To elucidate the biological role of TMEM115, I started with a proteomic approach, a BioID proximity screen, to identify novel interactors for TMEM115 under different physiologically relevant conditions. A number of binding partners were identified in the BioID screen and validated with co-immunoprecipitation. These indicate intriguing possible functions of TMEM115, including regulating lipid biology, protein trafficking, protein degradation and ion channels. Given that several candidates are involved in protein trafficking, I used a secretome profile analysis method, the SPECS, for identifying TMEM115 dependent secreted proteins. A role of TMEM115 in regulating the fundamental de novo lipogenesis pathway, the SCAP-SREBP pathway (Freeman lab unpublished data), had been identified during the course of my project. Pursuing this, I investigated the possible relationship between TMEM115, SCAP and the novel interactor, p62; the results suggest that TMEM115 may be involved in regulating lipid homeostasis by modulating SCAP levels through the proteasomal degradation machinery.
Subjects/Keywords: 572
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APA ·
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MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shen, X. (2017). Characterising the rhomboid-like protein TMEM115. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:171e08c3-15f1-4d09-ba59-01b2007f140c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740827
Chicago Manual of Style (16th Edition):
Shen, Xin. “Characterising the rhomboid-like protein TMEM115.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:171e08c3-15f1-4d09-ba59-01b2007f140c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740827.
MLA Handbook (7th Edition):
Shen, Xin. “Characterising the rhomboid-like protein TMEM115.” 2017. Web. 04 Mar 2021.
Vancouver:
Shen X. Characterising the rhomboid-like protein TMEM115. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:171e08c3-15f1-4d09-ba59-01b2007f140c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740827.
Council of Science Editors:
Shen X. Characterising the rhomboid-like protein TMEM115. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:171e08c3-15f1-4d09-ba59-01b2007f140c ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740827
University of Oxford
7.
Islam, Md. Saiful.
Structural and functional studies on human oxygenases.
Degree: PhD, 2017, University of Oxford
URL: https://ora.ox.ac.uk/objects/uuid:266a901a-8e9d-48b3-aa54-99fd463da2bd
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740840
► The work described in this thesis focused on 2-oxoacid-dependent oxygenase enzymes. Most of the work focused on iron- and 2-oxoglutarate (2OG)-dependent oxygenases including JMJD6 and…
(more)
▼ The work described in this thesis focused on 2-oxoacid-dependent oxygenase enzymes. Most of the work focused on iron- and 2-oxoglutarate (2OG)-dependent oxygenases including JMJD6 and JMJD5, which are human enzymes of unassigned or controversial functions. Work was carried out also on human 4-hydroxyphenylpyruvate dioxygenase (HPPD), which is a structurally distinct 2-oxoacid oxygenase involved in tyrosine catabolism. The work involved protein purification, biophysical analysis, substrate screening, and inhibitor profiling. Chapter 1 gives an introduction to 2OG oxygenases summarizing their functions, structures, and mechanisms. Chapters 2-6 describe functional assignment, structural, and inhibition studies on JMJD6, which has been previously reported as phosphatidylserine receptor (PTDSR), as an N-methyl arginine demethylase, and as a lysyl-hydroxylase. The overall results using peptide as substrate support the assignment of JMJD6 as lysyl C-5 hydroxylase. Crystallographic studies reveal JMJD6 to be more similar to the JmjC hydroxylases than demethylases. JMJD6 was found to act on sequences of substrates including splicing regulatory (SR) proteins, such as U2AF65 (U2 small nuclear ribonucleoprotein auxiliary factor 65 kDa subunit), LUC7L2 (putative RNA binding protein luc 7-like 2), and CROP (cisplatin resistance-associated overexpressed protein). It also acted on sequences of substrates including p53, estrogen receptor α(ERα), and von Hippel-Lindau (VHL). There was no evidence for JMJD6-catalysed demethylation activity either on N-methyl arginine- or N-methyl lysine-residues. Studies on the non-catalytic domain of JMJD6 reveal a role of the polyserine domain in regulating catalytic activity. Structural and kinetic studies reveal how JMJD6 is inhibited by the structural analogues of 2OG. Chapters 7-8 describe crystallographic and other studies on JMJD5, which has been assigned as an arginine residue C-3 hydroxylase, and N-methyl lysine demethylase. The results support the assignment of JMJD5 as a hydroxylase rather than demethylase and will enable the development of selective JMJD5 inhibitors. Chapter 9 describes studies on human HPPD from crystallographic and inhibition perspectives. The results highlight common features at the active sites of the two classes of human 2-oxoacid oxygenases. Overall, the results inform on the functions of JMJD6 and JMJD5 as hydroxylases and will enable the development of selective inhibitors of them for use in target validation and the assignment of their biological roles.
Subjects/Keywords: 572
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APA (6th Edition):
Islam, M. S. (2017). Structural and functional studies on human oxygenases. (Doctoral Dissertation). University of Oxford. Retrieved from https://ora.ox.ac.uk/objects/uuid:266a901a-8e9d-48b3-aa54-99fd463da2bd ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740840
Chicago Manual of Style (16th Edition):
Islam, Md Saiful. “Structural and functional studies on human oxygenases.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
https://ora.ox.ac.uk/objects/uuid:266a901a-8e9d-48b3-aa54-99fd463da2bd ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740840.
MLA Handbook (7th Edition):
Islam, Md Saiful. “Structural and functional studies on human oxygenases.” 2017. Web. 04 Mar 2021.
Vancouver:
Islam MS. Structural and functional studies on human oxygenases. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: https://ora.ox.ac.uk/objects/uuid:266a901a-8e9d-48b3-aa54-99fd463da2bd ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740840.
Council of Science Editors:
Islam MS. Structural and functional studies on human oxygenases. [Doctoral Dissertation]. University of Oxford; 2017. Available from: https://ora.ox.ac.uk/objects/uuid:266a901a-8e9d-48b3-aa54-99fd463da2bd ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740840
University of East Anglia
8.
Pinchbeck, Benjamin.
Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA.
Degree: PhD, 2016, University of East Anglia
URL: https://ueaeprints.uea.ac.uk/id/eprint/64218/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.721047
► Paracoccus denitrificans, a model Alphaproteobacteria soil denitrifier, can grow solely on nitrate or nitrite as inorganic nitrogen sources using a specialised cytoplasmic assimilatory nitrate/nitrite reducing…
(more)
▼ Paracoccus denitrificans, a model Alphaproteobacteria soil denitrifier, can grow solely on nitrate or nitrite as inorganic nitrogen sources using a specialised cytoplasmic assimilatory nitrate/nitrite reducing pathway; Nas. This growth capability is phylogenetically represented throughout heterotrophic and autotrophic bacteria, plants and fungi. Whilst this metabolism has been extensively studied in the latter two, the regulatory mechanisms by which organoheterotrophic bacteria govern this nitrate-dependant metabolism are less understood. The work conducted here primarily investigated genetic regulation of Nas expression in P. denitrificans. In Gram-negative bacteria, transcription of proteins required to import and reduce nitrate/nitrite to ammonium, for nitrogen assimilation, are subject to dual control; promotion in the absence of ammonium by the general nitrogen regulatory system, NtrBC, and nitrate-induced transcriptional anti-termination by the two-component, NasT-NasS complex. Here, a hypothetical gene, nifR3, conserved with the ntr cluster throughout Alphaproteobacteria, was shown to regulate Nas biosynthesis. We report nifR3 encodes a nitrogen-responsive, tRNA-dihydrouridine synthase required for nasABGHC translation. Genomic deletion of nifR3 from P. denitrificans resulted in the lethal loss of nitrate assimilation and severe deficiency of dihydrouridine in tRNA, restored by genetic complementation of nifR3 in trans. Pure NifR3 harboured an FMN cofactor and reversibly catalysed NADH-dependant reduction of uridine, a physiological important post-transcriptional modification. Native band-shift assays using an isolated tRNA fraction of P. denitrificans identified specific targets of NifR3: mature tRNA transcripts encoding PheGAA, LysUUU and TrpCCA. This novel regulatory role of bacterial NifR3 and tRNA-dihydrouridine formation concerning post-transcriptional fine-turning of protein expression will be discussed throughout this thesis, in addition to the function of several other nitrogen-responsive proteins explored here. Separately, we demonstrated that NarJ, the molybdenum-chaperone for biogenesis of respiratory nitrate reductase, NarG, performs an unprecedented wide-spread maturation role of non-Nar nitrate reductases. Here, we found NarJ is solely responsible for fully assembling the functional assimilatory nitrate reductase, NasC, complete with cofactors, even under aerobic conditions.
Subjects/Keywords: 572
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APA (6th Edition):
Pinchbeck, B. (2016). Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA. (Doctoral Dissertation). University of East Anglia. Retrieved from https://ueaeprints.uea.ac.uk/id/eprint/64218/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.721047
Chicago Manual of Style (16th Edition):
Pinchbeck, Benjamin. “Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA.” 2016. Doctoral Dissertation, University of East Anglia. Accessed March 04, 2021.
https://ueaeprints.uea.ac.uk/id/eprint/64218/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.721047.
MLA Handbook (7th Edition):
Pinchbeck, Benjamin. “Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA.” 2016. Web. 04 Mar 2021.
Vancouver:
Pinchbeck B. Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA. [Internet] [Doctoral dissertation]. University of East Anglia; 2016. [cited 2021 Mar 04].
Available from: https://ueaeprints.uea.ac.uk/id/eprint/64218/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.721047.
Council of Science Editors:
Pinchbeck B. Regulation of nitrate and nitrite assimilation in Paracoccus denitrificans at the level of RNA. [Doctoral Dissertation]. University of East Anglia; 2016. Available from: https://ueaeprints.uea.ac.uk/id/eprint/64218/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.721047
9.
Elazzouzi, Mowafag F.
Investigation of selected autophagic proteins and the effect of tPS1-GFP expression.
Degree: PhD, 2015, Sheffield Hallam University
URL: http://shura.shu.ac.uk/19678/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741520
► Normally, the balance between the production and degradation of cellular proteins is necessary for the cell to exist. One of the most important pathways by…
(more)
▼ Normally, the balance between the production and degradation of cellular proteins is necessary for the cell to exist. One of the most important pathways by which the largest number of cytosolic and misfolded proteins is degraded is the autophagy-lysosome pathway. A defect in this process may result in accumulation and aggregation of proteins leading to cellular toxicity and subsequently neurodegenerative diseases. Previous work by Anderson (2003) with a truncated presenillin 1 construct, in HEK293 cell line showed structural changes in the cell in the early stages of autophagy. However, it seems that the autophagic process had failed to clear the presenilin-1 aggregates as would be expected in the normal state and appeared to lead to cell death. The work presented in this thesis primarily attempts to investigate, in term of subcellular localization, the influence of truncated PS1, expressed in HEK293 cells, on selected autophagy regulators (mTOR, raptor and LC3 proteins) and subsequently on the autophagy process. To investigate this, many different commercial antibodies were characterized against whole cell lysates from three different cell lines (NRK, MCF-7 and HEK293) using western blotting to obtain specific antibodies for mTOR, raptor and LC3. Then, the selected antibodies were used in dual label immunocytochemistry with mitochondrial antibody and wheat germ agglutinin (as a Golgi marker) to determine the subcellular localizations of mTOR, raptor and LC3 in non-autophagic HEK293 cells. To study the behaviour of the proteins of interest during autophagy of untransfected cells, HEK293 cells were rapamycin treated or serum starved. To compare the observed results with the behaviour of the proteins after the transfection, a truncated PS1-GFP construct was transiently transfected into HEK293 cells. Also, the subcellular localizations of the proteins were determined by dual label ICC.The data obtained suggests that in non-autophagic HEK293 cells, mTOR appears to be localized to mitochondria, raptor to the cytoplasm and LC3 to Golgi apparatus. Rapamycin treatment and serum starvation have the same influence on the behaviour of these proteins. In both cases, mTOR remained localized to mitochondria (no effect), raptor protein partially moved from the cytoplasm to the perinuclear area (similar to mitochondrial distribution) and some of the LC3 protein diffused to the cytoplasm, while most of it remained localized to the Golgi apparatus. Following the transfection, the observable data suggest that interactions between truncated PS1 and mTOR, raptor and LC3 might be occurring. It seems that truncated PS1 has no influence on the subcellular localizations of mTOR and raptor proteins (similar to mitochondrial distribution). However, in the case of LC3 protein, it seems that the protein has partially moved from the Golgi apparatus to interact with truncated PS1 in a new subcellular localization which is similar to the subcellular localizations of mTOR and raptor. The suggested interactions between truncated PS1 and mTOR, raptor…
Subjects/Keywords: 572
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APA (6th Edition):
Elazzouzi, M. F. (2015). Investigation of selected autophagic proteins and the effect of tPS1-GFP expression. (Doctoral Dissertation). Sheffield Hallam University. Retrieved from http://shura.shu.ac.uk/19678/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741520
Chicago Manual of Style (16th Edition):
Elazzouzi, Mowafag F. “Investigation of selected autophagic proteins and the effect of tPS1-GFP expression.” 2015. Doctoral Dissertation, Sheffield Hallam University. Accessed March 04, 2021.
http://shura.shu.ac.uk/19678/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741520.
MLA Handbook (7th Edition):
Elazzouzi, Mowafag F. “Investigation of selected autophagic proteins and the effect of tPS1-GFP expression.” 2015. Web. 04 Mar 2021.
Vancouver:
Elazzouzi MF. Investigation of selected autophagic proteins and the effect of tPS1-GFP expression. [Internet] [Doctoral dissertation]. Sheffield Hallam University; 2015. [cited 2021 Mar 04].
Available from: http://shura.shu.ac.uk/19678/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741520.
Council of Science Editors:
Elazzouzi MF. Investigation of selected autophagic proteins and the effect of tPS1-GFP expression. [Doctoral Dissertation]. Sheffield Hallam University; 2015. Available from: http://shura.shu.ac.uk/19678/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.741520
University of Leeds
10.
Kreuz, Sarah.
The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia.
Degree: PhD, 2015, University of Leeds
URL: http://etheses.whiterose.ac.uk/9143/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651246
► Protein kinases are central mediators of signal transduction pathways and transcriptional regulation. Lymphoid malignancies are characterised by aberrant activation of key signal transduction pathways and…
(more)
▼ Protein kinases are central mediators of signal transduction pathways and transcriptional regulation. Lymphoid malignancies are characterised by aberrant activation of key signal transduction pathways and specific gene expression programmes. Consequently, targeting kinases involved in these signal transduction pathways is a promising therapeutic strategy. Because gene expression is regulated at the level of chromatin, the aim of this study was to assess the effects of chromatin-modifying kinases on histone phosphorylation and transcriptional regulation in B cell lymphoma and the consequences of kinase inhibition for tumour cell viability and the chromatin structure of target genes. The kinase PIM1, whose mRNA is highly expressed in the aggressive activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL), but not germinal centre B cell-like DLBCL (GCB-DLBCL), has been shown to associate with the transcription factor MYC and to regulate the expression of MYC target genes by phosphorylating histone H3S10. Therefore, effects of PIM1 on viability and gene expression were evaluated in ABC-DLBCL and in the MYC-dependent Burkitt lymphoma (BL). However, pan-PIM kinase inhibition or knockdown of PIM1 did not effectively reduce viability of ABC-DLBCL or Burkitt lymphoma cell lines. Further, the expression of the MYC- and PIM1-bound GNL3 gene was largely unaffected by alterations in PIM kinase levels or activity. In conclusion, PIM kinases do not seem to be bona fide therapeutical targets in DLBCL and BL. The second part of this project aimed to understand the effects of Ibrutinib on chromatin structure in chronic lymphocytic leukaemia (CLL) cells. Ibrutinib inhibits Bruton’s tyrosine kinase, and thus B cell receptor (BCR) signalling, and is currently being tested in clinical trials for the treatment of CLL. In vitro, Ibrutinib inhibited BCR-induced gene expression and histone H3T6 and T11 phosphorylation. A possible kinase targeting H3T6 and H3T11 downstream of the BCR might be zipper-interacting protein kinase (ZIPK), a ZIPK inhibitor blocked H3T6p and H3T11p and gene expression. Short-term Ibrutinib treatment appeared to inhibit histone turnover but did not reduce H3K4me3, H3K9ac, H2A.Z or POL II recruitment at target genes, indicating that it inhibits only some aspects of transcription. In contrast, long-term Ibrutinib treatment decreased H3K4me3 and H3K9ac in promoter regions, possibly by an indirect, gene silencing-dependent mechanism. In summary, the results suggest that Ibrutinib blocks progression of CLL by inhibiting only some branches of BCR signalling and interestingly, many transcription-associated changes to the chromatin remain unaltered, while transcription is effectively inhibited.
Subjects/Keywords: 572
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APA (6th Edition):
Kreuz, S. (2015). The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia. (Doctoral Dissertation). University of Leeds. Retrieved from http://etheses.whiterose.ac.uk/9143/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651246
Chicago Manual of Style (16th Edition):
Kreuz, Sarah. “The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia.” 2015. Doctoral Dissertation, University of Leeds. Accessed March 04, 2021.
http://etheses.whiterose.ac.uk/9143/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651246.
MLA Handbook (7th Edition):
Kreuz, Sarah. “The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia.” 2015. Web. 04 Mar 2021.
Vancouver:
Kreuz S. The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia. [Internet] [Doctoral dissertation]. University of Leeds; 2015. [cited 2021 Mar 04].
Available from: http://etheses.whiterose.ac.uk/9143/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651246.
Council of Science Editors:
Kreuz S. The role of histone kinases in controlling transcription in B cell lymphoma and leukaemia. [Doctoral Dissertation]. University of Leeds; 2015. Available from: http://etheses.whiterose.ac.uk/9143/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.651246
University of Leeds
11.
Arrata, Irene Jeanne Marie.
Towards bionic proteins.
Degree: PhD, 2017, University of Leeds
URL: http://etheses.whiterose.ac.uk/17171/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715045
► De novo design of foldamers is a current challenge in chemical biology. Overcoming it is essential in order to expand the protein toolbox and access…
(more)
▼ De novo design of foldamers is a current challenge in chemical biology. Overcoming it is essential in order to expand the protein toolbox and access “bionic proteins”, i.e. proteins comprising non-natural segments, with enhanced biological functions. Since the alpha-helix represents the most abundant motif in protein structure, alpha-helix mimicry is a key approach to building foldamers and a stepping-stone towards generating bionic proteins. The current state-of-the-art on bottom-up foldamer synthesis for the mimicry of alpha-helices is described in Chapter 1. The Wilson Group focuses on aromatic oligoamide proteomimetics for the modulation of protein-protein interactions (PPIs) involved in known diseases. The work presented in this thesis aimed at building a basis towards the elaboration of bionic proteins, by proving that such proteomimetics can be used to build novel 3-dimensional constructs. 3-O-alkylated and N-alkylated oligobenzamides with complementary charged side-chains were designed to produce self-assembling foldamers. The synthesis and conformational study of dimers and trimers is reported in Chapter 2. This forms the groundwork towards generating proteomimetic-based coiled coils. An Affimer is a non-antibody-based scaffold, used in tandem with phage display. A small library of biotinylated N-alkylated proteomimetic inhibitors of p53/hDM2 was screened against an Affimer library. The investigation of the Affimer/foldamer interactions are reported in Chapter 3. Taken together, these results demonstrate that aromatic oligoamides are suitable building blocks for producing non-natural peptide sequences in order to generate bionic proteins.
Subjects/Keywords: 572
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APA (6th Edition):
Arrata, I. J. M. (2017). Towards bionic proteins. (Doctoral Dissertation). University of Leeds. Retrieved from http://etheses.whiterose.ac.uk/17171/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715045
Chicago Manual of Style (16th Edition):
Arrata, Irene Jeanne Marie. “Towards bionic proteins.” 2017. Doctoral Dissertation, University of Leeds. Accessed March 04, 2021.
http://etheses.whiterose.ac.uk/17171/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715045.
MLA Handbook (7th Edition):
Arrata, Irene Jeanne Marie. “Towards bionic proteins.” 2017. Web. 04 Mar 2021.
Vancouver:
Arrata IJM. Towards bionic proteins. [Internet] [Doctoral dissertation]. University of Leeds; 2017. [cited 2021 Mar 04].
Available from: http://etheses.whiterose.ac.uk/17171/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715045.
Council of Science Editors:
Arrata IJM. Towards bionic proteins. [Doctoral Dissertation]. University of Leeds; 2017. Available from: http://etheses.whiterose.ac.uk/17171/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.715045
University of Leeds
12.
Antanaviciute, Agne.
Novel algorithm development for 'next generation' sequencing data analysis.
Degree: PhD, 2017, University of Leeds
URL: http://etheses.whiterose.ac.uk/20734/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745536
► In recent years, the decreasing cost of ‘Next generation’ sequencing has spawned numerous applications for interrogating whole genomes and transcriptomes in research, diagnostic and forensic…
(more)
▼ In recent years, the decreasing cost of ‘Next generation’ sequencing has spawned numerous applications for interrogating whole genomes and transcriptomes in research, diagnostic and forensic settings. While the innovations in sequencing have been explosive, the development of scalable and robust bioinformatics software and algorithms for the analysis of new types of data generated by these technologies have struggled to keep up. As a result, large volumes of NGS data available in public repositories are severely underutilised, despite providing a rich resource for data mining applications. Indeed, the bottleneck in genome and transcriptome sequencing experiments has shifted from data generation to bioinformatics analysis and interpretation. This thesis focuses on development of novel bioinformatics software to bridge the gap between data availability and interpretation. The work is split between two core topics – computational prioritisation/identification of disease gene variants and identification of RNA N6 -adenosine Methylation from sequencing data. The first chapter briefly discusses the emergence and establishment of NGS technology as a core tool in biology and its current applications and perspectives. Chapter 2 introduces the problem of variant prioritisation in the context of Mendelian disease, where tens of thousands of potential candidates are generated by a typical sequencing experiment. Novel software developed for candidate gene prioritisation is described that utilises data mining of tissue-specific gene expression profiles (Chapter 3). The second part of chapter investigates an alternative approach to candidate variant prioritisation by leveraging functional and phenotypic descriptions of genes and diseases from multiple biomedical domain ontologies (Chapter 4). Chapter 5 discusses N6 AdenosineMethylation, a recently re-discovered posttranscriptional modification of RNA. The core of the chapter describes novel software developed for transcriptome-wide detection of this epitranscriptomic mark from sequencing data. Chapter 6 presents a case study application of the software, reporting the previously uncharacterised RNA methylome of Kaposi’s Sarcoma Herpes Virus. The chapter further discusses a putative novel N6-methyl-adenosine -RNA binding protein and its possible roles in the progression of viral infection.
Subjects/Keywords: 572
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APA (6th Edition):
Antanaviciute, A. (2017). Novel algorithm development for 'next generation' sequencing data analysis. (Doctoral Dissertation). University of Leeds. Retrieved from http://etheses.whiterose.ac.uk/20734/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745536
Chicago Manual of Style (16th Edition):
Antanaviciute, Agne. “Novel algorithm development for 'next generation' sequencing data analysis.” 2017. Doctoral Dissertation, University of Leeds. Accessed March 04, 2021.
http://etheses.whiterose.ac.uk/20734/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745536.
MLA Handbook (7th Edition):
Antanaviciute, Agne. “Novel algorithm development for 'next generation' sequencing data analysis.” 2017. Web. 04 Mar 2021.
Vancouver:
Antanaviciute A. Novel algorithm development for 'next generation' sequencing data analysis. [Internet] [Doctoral dissertation]. University of Leeds; 2017. [cited 2021 Mar 04].
Available from: http://etheses.whiterose.ac.uk/20734/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745536.
Council of Science Editors:
Antanaviciute A. Novel algorithm development for 'next generation' sequencing data analysis. [Doctoral Dissertation]. University of Leeds; 2017. Available from: http://etheses.whiterose.ac.uk/20734/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745536
Heriot-Watt University
13.
Saleeb, Rebecca S.
A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy.
Degree: PhD, 2017, Heriot-Watt University
URL: http://hdl.handle.net/10399/3317
► Cell survival requires the turnover of toxic cellular material and recycling of biomolecules in low nutrient conditions. An efficient degradation system is therefore essential for…
(more)
▼ Cell survival requires the turnover of toxic cellular material and recycling of biomolecules in low nutrient conditions. An efficient degradation system is therefore essential for disease prevention and its dysfunction has been linked to both neurodegeneration and oncogenesis. Bulk degradation is accomplished through the collection of cytoplasmic material in a unique sequestration vesicle, which forms de novo and subsequently deposits cargo in the lysosome for degradation. This process, known as autophagy, therefore requires membrane fusion between the autophagosomal vesicle and the lysosome. SNARE proteins mediate membrane fusion events and therefore their careful regulation ensures the proper organisation of the membrane trafficking network. The SNARE proteins governing autophagosome clearance have been identified as syntaxin 17, SNAP29 and VAMP8 and SNARE assembly appears to be positively regulated by VPS33A. This well established model of SNARE-mediated autophagosome clearance has not, however, been demonstrated within the spatiotemporal framework of the cell and little is known about how VPS33A modulates SNARE function. The research presented in this thesis therefore aims to determine the applicability of the proposed SNARE model within the cellular environment and to investigate the regulatory mechanisms controlling syntaxin 17 function. To accomplish this, carefully validated fluorescence colocalisation and time-resolved fluorescence lifetime imaging techniques were primarily employed. The limitations of these techniques were also considered for data interpretation and a novel prototype SPAD array technology, designed for high-speed time-correlated single photon counting, was trialled for widefield FLIM-FRET. FLIM-FRET revealed that VAMP8 has been incorrectly assigned as the dominant autophagosomal R-SNARE and VPS33A studies evidence a multi-modal regulation of Stx17 that diverges from other studied syntaxin family modulation mechanisms. A new model of SNAREmediated autophagosome clearance is therefore proposed, where syntaxin 17 engages with SNAP29 and VAMP7 to drive membrane fusion with the endolysosome in a manner governed by VPS33A and dependent on the phosphorylation status of syntaxin 17.
Subjects/Keywords: 572
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Export
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APA (6th Edition):
Saleeb, R. S. (2017). A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy. (Doctoral Dissertation). Heriot-Watt University. Retrieved from http://hdl.handle.net/10399/3317
Chicago Manual of Style (16th Edition):
Saleeb, Rebecca S. “A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy.” 2017. Doctoral Dissertation, Heriot-Watt University. Accessed March 04, 2021.
http://hdl.handle.net/10399/3317.
MLA Handbook (7th Edition):
Saleeb, Rebecca S. “A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy.” 2017. Web. 04 Mar 2021.
Vancouver:
Saleeb RS. A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy. [Internet] [Doctoral dissertation]. Heriot-Watt University; 2017. [cited 2021 Mar 04].
Available from: http://hdl.handle.net/10399/3317.
Council of Science Editors:
Saleeb RS. A study of SNARE-mediated autophagosome clearance using fluorescence lifetime microscopy. [Doctoral Dissertation]. Heriot-Watt University; 2017. Available from: http://hdl.handle.net/10399/3317
University of Leicester
14.
Yaseen, Sadam Salim.
Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement.
Degree: PhD, 2015, University of Leicester
URL: https://figshare.com/articles/Deciphering_the_molecular_composition_of_two_independent_activation_cascades_of_the_lectin_pathway_of_complement/10230191
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745814
► The lectin pathway of complement activation is driven by pattern recognition molecules that direct activation of three different effector enzymes, called MASP-1, MASP-2 and MASP-3…
(more)
▼ The lectin pathway of complement activation is driven by pattern recognition molecules that direct activation of three different effector enzymes, called MASP-1, MASP-2 and MASP-3 (for Mannan binding lectin Associated Serine Protease). They drive complement activation through two independently operating effector arms. One effector arm (LEA-1) amplifies complement activation through MASP-3 dependent initiation of the alternative pathway amplification loop, while the second effector arm (LEA-2) is MASP-2 dependent and drives complement activation through the lectin pathway C3 and C5 convertases, C4bC2a and C4bC2a (C3b)n. Recently, a residual MASP-2 dependent C4-bypass route to activate C3 has been described in C4 deficient individuals. The first part of this thesis defines the molecular mechanism behind this C4-bypass activation route and demonstrates that MASP-2 can directly cleave native C3 to deposit C3b and iC3b on activator surfaces. The second part of this thesis studied the natural substrates and activators of MASP-3 to elucidate the sequence of molecular events that lead to alternative pathway activation via LEA-1. My results demonstrate that MASP-3 can be activated by both MASP-1 and MASP-2 and that activated MASP- 3 directly cleaves pro-FD, but not zymogen FB. While reconstitution of the deficient alternative pathway functional activity in MASP-1/-3 deficient mice could not be achieved by adding recombinant MASP-1, addition of either enzymatically active MASP-3 or injection of zymogen MASP-3 into these mice restored alternative pathway functional activity, underlining that MASP-3 is the predominant enzyme that drives LEA-1. Finally, the important role of MASP-1 and MASP-3 in the innate immune response to infection was demonstrated through the dramatically increased susceptibility of MASP-1/-3 deficient mice to S. pneumoniae infection. Notably, the defective C3b/iC3b opsonization of S. pneumoniae in MASP-1/-3 deficient mouse serum could be restored by reconstitution with recombinant MASP-3.
Subjects/Keywords: 572
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APA (6th Edition):
Yaseen, S. S. (2015). Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement. (Doctoral Dissertation). University of Leicester. Retrieved from https://figshare.com/articles/Deciphering_the_molecular_composition_of_two_independent_activation_cascades_of_the_lectin_pathway_of_complement/10230191 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745814
Chicago Manual of Style (16th Edition):
Yaseen, Sadam Salim. “Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement.” 2015. Doctoral Dissertation, University of Leicester. Accessed March 04, 2021.
https://figshare.com/articles/Deciphering_the_molecular_composition_of_two_independent_activation_cascades_of_the_lectin_pathway_of_complement/10230191 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745814.
MLA Handbook (7th Edition):
Yaseen, Sadam Salim. “Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement.” 2015. Web. 04 Mar 2021.
Vancouver:
Yaseen SS. Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement. [Internet] [Doctoral dissertation]. University of Leicester; 2015. [cited 2021 Mar 04].
Available from: https://figshare.com/articles/Deciphering_the_molecular_composition_of_two_independent_activation_cascades_of_the_lectin_pathway_of_complement/10230191 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745814.
Council of Science Editors:
Yaseen SS. Deciphering the molecular composition of two independent activation cascades of the lectin pathway of complement. [Doctoral Dissertation]. University of Leicester; 2015. Available from: https://figshare.com/articles/Deciphering_the_molecular_composition_of_two_independent_activation_cascades_of_the_lectin_pathway_of_complement/10230191 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.745814
15.
Eccleston, Ruth Charlotte.
A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors.
Degree: PhD, 2017, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10038760/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747069
► Major histocompatability complex class I (MHC-I) proteins present short fragments of pathogenic or cancerous proteins (peptides) on the surface of infected cells for recognition by…
(more)
▼ Major histocompatability complex class I (MHC-I) proteins present short fragments of pathogenic or cancerous proteins (peptides) on the surface of infected cells for recognition by T lymphocytes which are stimulated upon recognition of foreign peptides. Due to the diversity of peptide sequences and the sequence-specificity of MHC-I alleles, being able to determine which peptides will be presented by which MHC-I alleles and in what proportion could be important for the development of vaccines and treatments based on the presented peptiodome. Machine learning tools, trained on experimental data, are widely used to predict immunogenic peptides. However they are unable to account for the impact the intracellular kinetics of the pathogenic or cancerous protein which will greatly influence the resultant peptidome. Here we describe a mechanistic model of peptide presentation, validated against experimental data, which accounts for intracellular peptide concentration, and can predict the relative cell surface presentation of competing peptides with varying affinities for MHC-I proteins. We demonstrate how combining this mechanistic model with the intracellular kinetics of HIV proteins can provide insight in to the experimentally reported immunogenicity of the viral protein Gag, and show how such a model can be used to predict the most abundant viral peptides presented on the cell surface. Similarly, we predict the HeLa cell peptidome and demonstrate how a simple metric can be used to approximate the abundance of a peptide based solely on protein synthesis and degradation, peptide-MHC affinity and proteasomal cleavage.
Subjects/Keywords: 572
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APA (6th Edition):
Eccleston, R. C. (2017). A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10038760/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747069
Chicago Manual of Style (16th Edition):
Eccleston, Ruth Charlotte. “A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors.” 2017. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/10038760/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747069.
MLA Handbook (7th Edition):
Eccleston, Ruth Charlotte. “A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors.” 2017. Web. 04 Mar 2021.
Vancouver:
Eccleston RC. A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors. [Internet] [Doctoral dissertation]. University College London (University of London); 2017. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/10038760/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747069.
Council of Science Editors:
Eccleston RC. A mechanistic model predicting cell surface presentation of peptides by MHC class I proteins, considering peptide competition, viral intracellular kinetics and host genotype factors. [Doctoral Dissertation]. University College London (University of London); 2017. Available from: https://discovery.ucl.ac.uk/id/eprint/10038760/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747069
University College London (University of London)
16.
Kelly, Joanna.
Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition.
Degree: PhD, 2018, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10045030/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747456
► The cell cycle is tightly regulated to safeguard the complete and equal division of the nuclear contents between the daughter cells. To ensure accurate segregation…
(more)
▼ The cell cycle is tightly regulated to safeguard the complete and equal division of the nuclear contents between the daughter cells. To ensure accurate segregation of the chromatin, DNA catenation generated during replication must be resolved by topoisomerase IIα (TopoIIα). In some tumour-derived cells, Protein kinase C epsilon (PKCε) has been shown to play a crucial role in mediating a delay signal at the metaphase-to-anaphase transition when catenation is still present, allowing time for catenation resolution prior to anaphase entry and sister chromatid separation. PKCε has also been shown to affect the decatenation process itself, with an increase in metaphase catenation being observed upon PKCε knock down or inhibition. Active PKCε is predominantly membrane associated as lipid binding is required for canonical activation. However, a lipid-independent activation pathway has been observed which involves complex formation with the scaffold protein 14-3-3. In this thesis, we have identified a second lipid-independent pathway. In mitosis, we have identified a caspase-mediated, proteolytic cleavage of PKCε within a chromatin-associated sub-compartment. The cleavage occurs at two distinct sites, one of which leads to the generation of a free kinase domain. Blocking PKCε cleavage at this site, via mutation or caspase-7 inhibition, results in a reduction in the PKCε dependent delay to the metaphase-to-anaphase transition. This can be rescued by artificially recapitulating the cleavage event. Cells expressing a non-cleavable PKCε also retain larger amounts of metaphase catenation, indicating that cleavage is required to support resolution as well as the delay. As both of these phenotypic responses require active PKCε this proteolytic cleavage represents a novel, non-canonical activation pathway. The mechanism by which the free kinase domain generated influences the response to TopoIIα inhibition is still to be fully resolved but phosphorylation of the key mitotic regulator Aurora B and subsequent phosphorylation of TopoIIα have been shown to play a crucial role. Due to an increased dependence on this response in a number of tumour-derived cells, identifying the pathways involved in its regulation may offer a potentially novel target for cancer therapeutics.
Subjects/Keywords: 572
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kelly, J. (2018). Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10045030/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747456
Chicago Manual of Style (16th Edition):
Kelly, Joanna. “Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition.” 2018. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/10045030/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747456.
MLA Handbook (7th Edition):
Kelly, Joanna. “Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition.” 2018. Web. 04 Mar 2021.
Vancouver:
Kelly J. Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition. [Internet] [Doctoral dissertation]. University College London (University of London); 2018. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/10045030/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747456.
Council of Science Editors:
Kelly J. Non-canonical PKCε activation is required for the cellular response to TopoIIα inhibition. [Doctoral Dissertation]. University College London (University of London); 2018. Available from: https://discovery.ucl.ac.uk/id/eprint/10045030/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747456
University College London (University of London)
17.
Walker-Gray, R. A.
Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase.
Degree: PhD, 2017, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/1553400/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746532
► Cyclic AMP (cAMP) is an ancient second messenger that is essential for many cellular processes including synaptic plasticity and control of heart rate and contractility.…
(more)
▼ Cyclic AMP (cAMP) is an ancient second messenger that is essential for many cellular processes including synaptic plasticity and control of heart rate and contractility. Cyclic AMP-dependent protein kinase (PKA) is the major intracellular receptor for cAMP. PKA consists of dimeric regulatory (R) subunits that bind and inhibit catalytic (C) subunits. PKA is activated upon binding of cAMP to the R subunits, which leads to the release of C subunits, and phosphorylation of intracellular protein substrates. An enduring challenge in cAMP research is to understand how PKA activity is directed to specific substrates, as the C subunits exhibit only limited substrate specificity in vitro. Elevations of cAMP are controlled in both space and time in the cell. This is achieved by the co-localization of enzymes for both the synthesis (cyclases) and breakdown (phosphodiesterases) of cAMP. Anchoring proteins are also essential for directing PKA to substrates in their immediate vicinity. However, a mechanism is yet to be established to explain how the activity of the C subunit of PKA is restrained following its dissociation from R subunits. This thesis details three parallel investigations that apply novel approaches with the shared aim of understanding how C subunit restraint is achieved. First, using quantitative immunoblotting in conjunction with purified PKA subunits, I investigated PKA subunit stoichiometry, finding that PKA R subunits typically outnumber C subunits by ~15-fold. Second, I developed a novel approach for monitoring R subunit isoform-specific association with C subunits in cells, with temporal precision. Comparative experiments using this approach and measurements with a fluorescent reporter of PKA activity show that only a small portion of C subunits need be dissociated to achieve high PKA activity. Third, I applied and developed a novel cross-linking coupled to mass spectrometry (XL-MS) protocol for analysis of the structure of PKA complexes. Insights include the likely orientation of PKA complexes that contain type II R (RII) subunits towards the membrane, and identification of a possible conformational change in PKA upon binding an anchoring protein. Together these experiments illuminate several aspects of PKA to show how the activity of this critical signalling enzyme is restrained within cells.
Subjects/Keywords: 572
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Walker-Gray, R. A. (2017). Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/1553400/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746532
Chicago Manual of Style (16th Edition):
Walker-Gray, R A. “Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase.” 2017. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/1553400/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746532.
MLA Handbook (7th Edition):
Walker-Gray, R A. “Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase.” 2017. Web. 04 Mar 2021.
Vancouver:
Walker-Gray RA. Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase. [Internet] [Doctoral dissertation]. University College London (University of London); 2017. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/1553400/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746532.
Council of Science Editors:
Walker-Gray RA. Investigation of mechanisms for restricting the activity of cyclic-AMP dependent protein kinase. [Doctoral Dissertation]. University College London (University of London); 2017. Available from: https://discovery.ucl.ac.uk/id/eprint/1553400/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746532
University College London (University of London)
18.
Livermore, T. M.
Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate.
Degree: PhD, 2016, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/1498711/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746202
► Inositol pyrophosphates and inorganic polyphosphate (polyP) represent two of the most phosphate-rich molecules in the cell. However, the synthesis, metabolism and function of these “high-energy”…
(more)
▼ Inositol pyrophosphates and inorganic polyphosphate (polyP) represent two of the most phosphate-rich molecules in the cell. However, the synthesis, metabolism and function of these “high-energy” molecules are not well understood. This work develops the amoeba, Dictyostelium discoideum, as a genetic model to study both classes of molecule. By applying improved polyacrylamide gel electrophoresis (PAGE) techniques, unlabelled inositol pyrophosphates and polyP extracted from D. discoideum have been visualised for the first time. Deletion of a range of inositol phosphate kinases reveals a complex synthetic pathway of the inositol pyrophosphates in the amoeba. Surprisingly, strains lacking the majority of inositol pyrophosphates do not display a dramatic phenotype. However, these cells retain low levels of inositol pyrophosphates. In fact, this work identified at least four enzymes capable of synthesising inositol pyrophosphates in the amoeba, including the novel inositol phosphate kinases IPKA and IPKB. In vitro, both IPKA and IPKB act as specific IP 7 kinases. However, in vivo both enzymes are catalytically flexible and are able to phosphorylate other substrates. In addition, PAGE technology allows the detection of polyP extracted from D. discoideum, revealing the unprecedented increase of polyP during development. Deletion of the Polyphosphate kinase (PPK)1 gene confirms this to be the only PPK in the amoeba. Deletion of PPK has a negative effect on the fitness of the amoeba, a phenotype underpinned by the ability of polyP to regulate primary metabolism. The ppk1-null strain fails to accumulate polyP during development and is defective in spore germination. Loss of polyP during the development of ppk1 is partially compensated by an increase in inositol pyrophosphates. These observations support a model in which there is a functional interplay between inositol pyrophosphates, polyP and primary metabolism.
Subjects/Keywords: 572
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APA ·
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Export
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APA (6th Edition):
Livermore, T. M. (2016). Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/1498711/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746202
Chicago Manual of Style (16th Edition):
Livermore, T M. “Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate.” 2016. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/1498711/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746202.
MLA Handbook (7th Edition):
Livermore, T M. “Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate.” 2016. Web. 04 Mar 2021.
Vancouver:
Livermore TM. Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate. [Internet] [Doctoral dissertation]. University College London (University of London); 2016. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/1498711/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746202.
Council of Science Editors:
Livermore TM. Developing Dictyostelium discoideum as a model to study the synthesis and metabolism of inositol pyrophosphates and inorganic polyphosphate. [Doctoral Dissertation]. University College London (University of London); 2016. Available from: https://discovery.ucl.ac.uk/id/eprint/1498711/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746202
University College London (University of London)
19.
Macabuag, N.
Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing.
Degree: PhD, 2015, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/1472878/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746037
► N-type voltage-gated calcium (CaV2.2) channels are expressed predominantly in the central and peripheral nervous systems and play a crucial role in neurotransmitter release. Expression of…
(more)
▼ N-type voltage-gated calcium (CaV2.2) channels are expressed predominantly in the central and peripheral nervous systems and play a crucial role in neurotransmitter release. Expression of these channels at the plasma membrane and in the membrane of presynaptic terminals is key for their function, however, how they are trafficked from the subcellular organelles is still poorly understood. In this study, trafficking of mutually-exclusive alternative splice variants of CaV2.2, containing either exon 37a or 37b at the proximal C-terminus and its mechanisms were examined. CaV2.2 with exon 37a (selectively expressed in nociceptors) reveals a significantly greater intracellular trafficking to the axons and plasma membrane of DRG neurons than CaV2.2 with exon 37b. Further examination of the amino acid sequence in exon 37 uncovers that the canonical binding motifs for adaptor protein 1 (AP-1), YxxΦ and [DE]xxxL[LI], present only in exon 37a are accountable for mediating the enhanced channel trafficking from the trans-Golgi network to the plasma membrane. Finally, the dopamine-2 receptor (D2R) and its agonist-induced activation, reveal differential effects on trafficking of these CaV2.2 isoforms. D2R slowed the endocytosis of CaV2.2 containing exon 37b but not exon 37a, and activation by the D2R-selective agonist quinpirole reversed the effect of the D2R. Disrupting the interaction between adaptor proteins and YxxΦ or [DE]xxxL[LI] in CaV2.2 perturbed these effects, suggesting that the interaction of adaptor proteins with CaV2.2 channels may also be key underlying mechanisms for differential trafficking of CaV2.2 splice variants, mediated by D2R. This study thus reveals key mechanisms involved in the trafficking of N-type calcium channels.
Subjects/Keywords: 572
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Macabuag, N. (2015). Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/1472878/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746037
Chicago Manual of Style (16th Edition):
Macabuag, N. “Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing.” 2015. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/1472878/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746037.
MLA Handbook (7th Edition):
Macabuag, N. “Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing.” 2015. Web. 04 Mar 2021.
Vancouver:
Macabuag N. Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing. [Internet] [Doctoral dissertation]. University College London (University of London); 2015. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/1472878/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746037.
Council of Science Editors:
Macabuag N. Trafficking of N-type voltage-gated calcium ion channels and their regulation by alternative splicing. [Doctoral Dissertation]. University College London (University of London); 2015. Available from: https://discovery.ucl.ac.uk/id/eprint/1472878/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746037
University College London (University of London)
20.
Koliopoulos, Marios Grigorios.
Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression.
Degree: PhD, 2017, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10038260/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747042
► Ubiquitination is a post-translational modification of proteins with broad regulatory roles across cellular biology. This process involves the addition of ubiquitin molecules on target proteins,…
(more)
▼ Ubiquitination is a post-translational modification of proteins with broad regulatory roles across cellular biology. This process involves the addition of ubiquitin molecules on target proteins, altering their cellular role and properties. Ubiquitination is performed by an enzymatic cascade consisting of three enzymes: ubiquitin activating enzymes (E1), ubiquitin conjugating enzymes (E2) and ubiquitin ligases (E3). The tripartite motif (TRIM) family of proteins constitutes one of the largest subfamilies of RING E3 ligases and the majority of them are contributing to the regulation of innate immune responses. They are characterized by a conserved tripartite motif in their N-terminal region which comprises a RING domain, one or two B-box domains and a coiled-coil region. Self-association is believed to be crucial for catalytic activity of TRIM proteins, however, the precise molecular mechanism underlying this observation remains elusive. The work presented in this thesis provides insights into the E3 ligase function of TRIM25 and shows how its oligomeric state is linked to its catalytic activity. The crystal structure of a complex between the TRIM25 RING domain and a ubiquitin-loaded E2 identifies the structural and mechanistic features that promote activation of E2~Ub allowing us to propose a model for the regulation of activity in the full-length protein. In the second part of this thesis, the molecular details of Influenza A NS1-mediated TRIM25 inhibition are presented. The crystal structures of NS1 bound to TRIM25 along with biochemical analysis allowed us to identify the interacting domains and propose a model for the inhibition of substrate ubiquitination during viral infection. The results of this project extend our understanding of the mechanism, structure and regulation of TRIM E3 ligases and their substrates, leading to increased chances of targeting specific steps of the ubiquitination pathway during disease.
Subjects/Keywords: 572
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Koliopoulos, M. G. (2017). Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10038260/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747042
Chicago Manual of Style (16th Edition):
Koliopoulos, Marios Grigorios. “Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression.” 2017. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/10038260/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747042.
MLA Handbook (7th Edition):
Koliopoulos, Marios Grigorios. “Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression.” 2017. Web. 04 Mar 2021.
Vancouver:
Koliopoulos MG. Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression. [Internet] [Doctoral dissertation]. University College London (University of London); 2017. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/10038260/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747042.
Council of Science Editors:
Koliopoulos MG. Structural and functional basis for TRIM25 E3 ligase catalytic activity and NS1-mediated suppression. [Doctoral Dissertation]. University College London (University of London); 2017. Available from: https://discovery.ucl.ac.uk/id/eprint/10038260/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747042
University College London (University of London)
21.
Pfeiffenberger, E.
Understanding and predicting the dynamics, folding and binding of proteins.
Degree: PhD, 2018, University College London (University of London)
URL: https://discovery.ucl.ac.uk/id/eprint/10041704/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747260
► Proteins are involved in all processes of life and their shapes, interactions and functions are governed by physical forces. A model with atomic resolution is…
(more)
▼ Proteins are involved in all processes of life and their shapes, interactions and functions are governed by physical forces. A model with atomic resolution is pivotal for the understanding of their mechanisms and how mutations perturb these. However, given the large variation of proteins and the limitations of experimental methods, in-silico approaches are the only viable solution. Presented here are a number of computational methods to predict their structure and binary interactions with atomic detail. Firstly, a machine-learning method was developed that models the recognition process of protein-protein binding to improve the identification of near-native binding sites. Secondly, a refinement method was developed to improve the structural accuracy of predicted monomers. An intra reside-residue contact map space was defined to perform more directed conformational exploration with metadynamics in order to find solutions that better resemble the native state. This method was extended to perform refinement of pre-docked heterodimers in order to predict the conformational transition from unbound to bound. Here, an inter residue-residue contact map space was defined between the interface of a receptor and a ligand. Following this extensive sampling of protein conformations by simulation, a recurrent neural network was defined and trained to predict the state changes during the sampling such that improved quality conformations can be identified. Finally, extensive in-silico biophysical experiments were performed to understand the mechanism of auto-phosphorylation for RET-kinase in wild-type and its deregulation by an oncogenic mutation.
Subjects/Keywords: 572
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APA (6th Edition):
Pfeiffenberger, E. (2018). Understanding and predicting the dynamics, folding and binding of proteins. (Doctoral Dissertation). University College London (University of London). Retrieved from https://discovery.ucl.ac.uk/id/eprint/10041704/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747260
Chicago Manual of Style (16th Edition):
Pfeiffenberger, E. “Understanding and predicting the dynamics, folding and binding of proteins.” 2018. Doctoral Dissertation, University College London (University of London). Accessed March 04, 2021.
https://discovery.ucl.ac.uk/id/eprint/10041704/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747260.
MLA Handbook (7th Edition):
Pfeiffenberger, E. “Understanding and predicting the dynamics, folding and binding of proteins.” 2018. Web. 04 Mar 2021.
Vancouver:
Pfeiffenberger E. Understanding and predicting the dynamics, folding and binding of proteins. [Internet] [Doctoral dissertation]. University College London (University of London); 2018. [cited 2021 Mar 04].
Available from: https://discovery.ucl.ac.uk/id/eprint/10041704/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747260.
Council of Science Editors:
Pfeiffenberger E. Understanding and predicting the dynamics, folding and binding of proteins. [Doctoral Dissertation]. University College London (University of London); 2018. Available from: https://discovery.ucl.ac.uk/id/eprint/10041704/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.747260
University of Oxford
22.
Law, Eleanor C.
Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins.
Degree: PhD, 2017, University of Oxford
URL: https://ora.ox.ac.uk/objects/uuid:843c6e38-fbc8-48a7-a61b-f6d93f7d3f7d
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740887
► Membrane proteins are an important class of drug targets, making up at least 25% of proteins in the human genome. In this thesis I investigated…
(more)
▼ Membrane proteins are an important class of drug targets, making up at least 25% of proteins in the human genome. In this thesis I investigated two aspects of alpha-helical membrane protein structures. Firstly, I investigated kinks in alpha-helices, many of which are thought to have functional roles. Kinks are changes of direction in helices, often defined in a binary fashion, but here I move towards defining them on a continuum. I found that kink angles are not generally a conserved property of homologues, pointing either to their not being functionally critical or to their function being related to conformational flexibility. I found correlation in kink angles and conformational change upon activation in GPCRs, reinforcing the belief that helix kinks are key, functional, flexible points in structures. Secondly, I turned to the biogenesis of alpha-helical membrane proteins, and how this might be used to improve structure prediction. These proteins are inserted into the membrane during the process of translation by the ribosome, therefore the N-terminus may be able to adopt its tertiary fold before the C-terminus is translated. I found a weak signal in a non-redundant set of structures that membrane proteins exhibit asymmetry between the N- and C-termini. This might be expected if they are folding cotranslationally, as had been seen in soluble proteins. Motivated by this, I predicted the structures of membrane proteins using SAINT2, a cotranslational structure prediction program, and achieved promising results. I developed SAINT2-ScafFold, which folds proteins around a rigid N-terminus, but the accuracy of prediction of the remaining protein was no better than when the entire chain was sampled. A membrane potential was implemented in SAINT2, which slightly improves the accuracy of models generated. Finally, the SAINT2-ScafFold method was applied to the completion of homology models that do not cover the entire target. An RMSD of less than 5 Å was achieved in more than half of the cases where a terminal transmembrane helix of membrane protein structures was predicted. This was an encouraging result for the prediction of membrane proteins from partial templates, and could easily be extended to soluble proteins.
Subjects/Keywords: 572
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Law, E. C. (2017). Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins. (Doctoral Dissertation). University of Oxford. Retrieved from https://ora.ox.ac.uk/objects/uuid:843c6e38-fbc8-48a7-a61b-f6d93f7d3f7d ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740887
Chicago Manual of Style (16th Edition):
Law, Eleanor C. “Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
https://ora.ox.ac.uk/objects/uuid:843c6e38-fbc8-48a7-a61b-f6d93f7d3f7d ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740887.
MLA Handbook (7th Edition):
Law, Eleanor C. “Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins.” 2017. Web. 04 Mar 2021.
Vancouver:
Law EC. Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: https://ora.ox.ac.uk/objects/uuid:843c6e38-fbc8-48a7-a61b-f6d93f7d3f7d ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740887.
Council of Science Editors:
Law EC. Computational studies of structural motifs and cotranslational folding mechanisms in membrane and soluble proteins. [Doctoral Dissertation]. University of Oxford; 2017. Available from: https://ora.ox.ac.uk/objects/uuid:843c6e38-fbc8-48a7-a61b-f6d93f7d3f7d ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740887
University of Oxford
23.
Ang, Jit Hang Jackie.
Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels.
Degree: PhD, 2017, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740888
► Biophysical techniques are widely used to determine the structure, function and ligand binding properties of a protein. However, their application to membrane proteins has been…
(more)
▼ Biophysical techniques are widely used to determine the structure, function and ligand binding properties of a protein. However, their application to membrane proteins has been limited due to the difficulty of obtaining sufficient purified sample. In this work, I use such methods to examine the thermostability and ligand binding properties of TREKs, two members of the family of tandem pore domain K+ channels important for the regulation of cellular excitability. Structures of TREK1 and TREK2 are available and thus when combined with such approaches may help guide the design of better ligands. I first successfully optimised the DSF method using the CPM dye for the detection of TREK ligands and found this to be a viable approach. In addition, direct binding detection methods such as SPR, ITC and Biolayer Interferometry were also investigated. A test case of 351 compounds derived from an FDA-approved pharmaceutical agent library were then screened against a range of K2P channels using the CPM assay. Several compounds were identified that appeared to thermostabilize the TREKs. These initial hits were further assessed using label-free DSF and functional studies on channel activity. Two compounds, cilnidipine and rimonabant were identified as a novel inhibitor and activator of TREK2 and TREK1 respectively. The findings are significant for the development of potent and selective binders for the TREKs and other membrane proteins, as they identify a viable workflow for identification of binders using biophysical methods.
Subjects/Keywords: 572
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APA (6th Edition):
Ang, J. H. J. (2017). Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740888
Chicago Manual of Style (16th Edition):
Ang, Jit Hang Jackie. “Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740888.
MLA Handbook (7th Edition):
Ang, Jit Hang Jackie. “Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels.” 2017. Web. 04 Mar 2021.
Vancouver:
Ang JHJ. Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740888.
Council of Science Editors:
Ang JHJ. Developing biophysical and structural methods for characterisation of small molecule modulators of K2P potassium channels. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:850d137b-6270-48d9-9eaa-ce6fb65dcbc4 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.740888
Cardiff University
24.
McPhee, Craig.
Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy.
Degree: PhD, 2016, Cardiff University
URL: http://orca.cf.ac.uk/111884/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742793
► Lipid domains provide a framework for localised functionality of the cellular membrane through transient coordination of certain lipids and membrane proteins into structurally distinct, stabilised…
(more)
▼ Lipid domains provide a framework for localised functionality of the cellular membrane through transient coordination of certain lipids and membrane proteins into structurally distinct, stabilised heterogeneous membrane regions. Present experimental studies fall short of conclusively proving lipid domain existence within the plasma membrane due to the lack of label-free, chemically sensitive nanoscale detection. Herein, I present my progress towards developing novel, label-free optical microscopy techniques to over- come these limitations. Giant unilamellar vesicles (GUVs) represent a simple model of cellular membranes and are well suited for the study of lipid domains. In this thesis, I discuss the demonstration of a novel, label free method to directly assess GUV lamellarity: Quantitative differential interference contrast microscopy (qDIC). Under qDIC, a contrast image is produced which encodes the difference in optical phase (hence optical path length) after propagation through two adjacent points of the sample. I show that, with appropriate data analysis applied to qDIC contrast images, we are able to measure membrane lamellarity directly with sub-nm precision. I then demonstrate the application of this method to static synthetic membranes exhibiting lipid domains: Planar Lipid Bilayer Patches (PLBPs). Sub-nm thickness differences (∼9Å) attributable to coexisting lipid domains are resolved and quantified. Overall, these results demonstrate that label free qDIC is a rapid, non-perturbing, sensitive and accurate method, providing an alternative to fluorescence microscopy, for quantitative studies of lipid domains in model membranes. Furthermore, I discuss correlative qDIC and Coherent Anti-Stokes Ra- man scattering microscopy (CARS) of PLBPs with lipid domains. CARS microscopy has emerged in the last decade as a powerful, chemically specific multi-photon imaging method which overcomes the sensitivity and speed limitations of spontaneous Raman scattering, and enables rapid quantitative analysis of lipids label-free. I demonstrate application of broadband hyper-spectral CARS imaging over the CH 2,3 stretching vibrational resonances, combined with in-house developed phase-corrected Kramers Krönig (PCKK) analysis, which allowed us to resolve and quantify the chemical components of lipid domains at the single bilayer level. Stimulated Raman loss (SRL) microscopy is an alternative, chemically specific, non-linear imaging modality recently implemented within our research group. In contrast to CARS microscopy, SRL rejects non-resonant background providing high contrast imaging of single lipid bilayers comparable to fluorescence imaging. I demonstrate early application of SRL at the single bilayer level across the CH 2,3 stretch region. During this project a number of notable achievements have been made. A novel qDIC method has been developed and utilised. CARS microscopy has been applied to determine lipid liquid phase at both single frequency and hyper-spectral imaging modalities. SRL microscopy has then been applied,…
Subjects/Keywords: 572
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APA (6th Edition):
McPhee, C. (2016). Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy. (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/111884/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742793
Chicago Manual of Style (16th Edition):
McPhee, Craig. “Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy.” 2016. Doctoral Dissertation, Cardiff University. Accessed March 04, 2021.
http://orca.cf.ac.uk/111884/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742793.
MLA Handbook (7th Edition):
McPhee, Craig. “Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy.” 2016. Web. 04 Mar 2021.
Vancouver:
McPhee C. Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy. [Internet] [Doctoral dissertation]. Cardiff University; 2016. [cited 2021 Mar 04].
Available from: http://orca.cf.ac.uk/111884/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742793.
Council of Science Editors:
McPhee C. Development and characterisation of synthetic model lipid membranes under linear and non-linear microscopy. [Doctoral Dissertation]. Cardiff University; 2016. Available from: http://orca.cf.ac.uk/111884/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742793
Cardiff University
25.
Lasota, Tomasz.
Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART).
Degree: PhD, 2017, Cardiff University
URL: http://orca.cf.ac.uk/111111/
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742811
► Real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) is becoming a widely accepted method for use in the field of molecular diagnostics. This method makes use…
(more)
▼ Real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) is becoming a widely accepted method for use in the field of molecular diagnostics. This method makes use of a highly robust core enzymology’s that are tolerant to sample derived inhibitors, along with a priming mechanisms that permit impeccable amplification sensitivities and specificities. These are well documented attributes associated with LAMP, but little is known about factors that drive and interfere with the reverse transcription of RT-LAMP assays. This study aims to address a number of factors that affect RNA amplification, including impedance of priming related to template structure, inhibition of polymerase activities by sample derived inhibitors and the general effect of assay chemistry and primer function with respect to reverse transcription. In addition to the chemistry optimisation and choice of polymerase (DNA / RT), the secondary structure innate within RNA, could significantly affect the efficiency of RT. Priming position and design would also need to be seriously considered with respect to the folding nature of these targets. Overtly, RT-LAMP showed an increased sensitivity to inhibition compared to its DNA counterpart. Similar observations of impeded RNA transcription were made during the development of an internal amplification control (IAC), which was designed to determine the exact inhibitory nature of any tested samples, in tandem with the RT-LAMP. This report clearly discloses that RT amplification controls must be synthesised ‘free of contaminating DNA’, to avoid poor characterisation of first strand DNA synthesis. Alternative ‘non-enzymatic methods’ of reporting amplification in real-time were compared to the bioluminescent assay real-time (BART) reporter; a well-established method of nucleic acid detection and quantification developed and patented by Lumora Ltd, Cambridgeshire (Fortes et al., 2013). Despite BARTs track record for detection of LAMP, its 4 indiscriminate reporting of amplification is of little use for duplexed assay characterisation, such as the IAC / RT-LAMP combined assay. Thus, methods of specific sequence detection were designed that could target single stranded elements of amplified products (STEMs and LOOP structures). It was demonstrated that the mechanism for RT-LAMP fluorescent probing ‘presented here’ was unique to this Thesis and does not fall under the guise of Taqman or other molecular beacon detection mechanisms. Together with BART, this new form of probing was successfully deployed to distinguish between true RT-LAMP and IAC afflicted amplifications. The possibility of utilising the LAMP/BART technologies for microRNA (miRNA) detection was also explored. Even though it is well known that miRNAs have crucial roles in responding to and regulating a wide range of biological and cellular processes, no real headway has been made in developing highly sensitive, low resource methods for their detection. Here we develop novel methods of miRNA detection capable of sensing picomolar levels…
Subjects/Keywords: 572
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APA ·
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MLA ·
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Export
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APA (6th Edition):
Lasota, T. (2017). Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART). (Doctoral Dissertation). Cardiff University. Retrieved from http://orca.cf.ac.uk/111111/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742811
Chicago Manual of Style (16th Edition):
Lasota, Tomasz. “Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART).” 2017. Doctoral Dissertation, Cardiff University. Accessed March 04, 2021.
http://orca.cf.ac.uk/111111/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742811.
MLA Handbook (7th Edition):
Lasota, Tomasz. “Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART).” 2017. Web. 04 Mar 2021.
Vancouver:
Lasota T. Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART). [Internet] [Doctoral dissertation]. Cardiff University; 2017. [cited 2021 Mar 04].
Available from: http://orca.cf.ac.uk/111111/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742811.
Council of Science Editors:
Lasota T. Enhanced molecular assays using strand-displacing polymerases and loop-mediated amplification (LAMP) with Bioluminescent Assay in Real Time (BART). [Doctoral Dissertation]. Cardiff University; 2017. Available from: http://orca.cf.ac.uk/111111/ ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.742811
26.
Hayward, K. L.
Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival.
Degree: PhD, 2014, University of the West of England, Bristol
URL: https://uwe-repository.worktribe.com/output/821546
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596049
► Introduction: Diabetes affects more than 346 million individuals worldwide. Some 90% of diabetics have type 2 diabetes mellitus, which is frequently associated with obesity and…
(more)
▼ Introduction: Diabetes affects more than 346 million individuals worldwide. Some 90% of diabetics have type 2 diabetes mellitus, which is frequently associated with obesity and hyperlipidemia as well as hyperglycaemia. There is ample evidence that fatty acids become toxic (lipotoxicity) when present at elevated concentrations for prolonged periods of time, although mechanisms are still not fully elucidated. Current diabetic medications do not tackle the underlying issue of β-cell death. New therapeutic strategies to more effectively combat and early deterioration of the β-cell mass and function due to lipotoxicity are thus required. Translationally Controlled Tumour Protein (TCTP) has been identified in a wide range of eukaryotic organisms and linked to many diverse cellular processes including acting as an anti-apoptotic protein. Ideally human islets of Langerhans would be used to investigate diabetes however they are not practical to use due to only being acquirable from cadavers. Rodent islets are more readily available however keeping the rodents require a lot of money, time and a license to ensure they are being cared for correctly. Monolayer cell lines have been created for the use in basic research which can be grown in a suspension forcing the cells to attach to each other forming 3D structures commonly referred to as pseudo-islets, have shown some promising results. Aims: (1) establishing an imaging-based assay for analysing characteristic changes in pancreatic β-cells lipotoxicity, (2) investigate the effect of TCTP in connection with lipotoxicity and (3) investigate possible alternatives to using cultured monolayer cells or isolated islets of Langerhans for diabetes research. Methods: MIN6, INS-1, HIT-T15, alpha TC 1 clone 6 cells and Hans-Wistar rat islets were incubated with were incubated with forskolin, exendin-4, thapsigargin, palmitate and oleate/palmitate (1:1) mix under stimulatory glucose conditions for 8, 24 or 48h to investigate lipid accumulation and/or protein changes. Lipid accumulation and cell death was investigated using ImageXpress 5000a and confocal microscopy. Changes in protein expression were investigated using immunoblots using a mouse monoclonal anti-TCTP antibody. Equal amount of protein was loaded into each lane and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) were used as internal controls. Changes in TCTP mRNA expression levels were investigated using TaqMan® with real-time PCR. Pancreatic spheroid formation was investigated using MIN6 and INS-1cells via three methods: agarose overlay, hanging drop/methyl cellulose, and confocal microscopy. Conclusions: Lipid accumulation could successfully be tracked in monolayer cells and islets of Langerhans. Proteomic and biochemical approaches revealed that TCTP level is regulated by glucose, palmitate and exendin-4. Regulation of TCTP by glucose and exendin-4 is cyto-protective. In contrast, high concentration of palmitate causes cell stress, reduction in TCTP protein…
Subjects/Keywords: 572
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APA ·
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MLA ·
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APA (6th Edition):
Hayward, K. L. (2014). Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival. (Doctoral Dissertation). University of the West of England, Bristol. Retrieved from https://uwe-repository.worktribe.com/output/821546 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596049
Chicago Manual of Style (16th Edition):
Hayward, K L. “Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival.” 2014. Doctoral Dissertation, University of the West of England, Bristol. Accessed March 04, 2021.
https://uwe-repository.worktribe.com/output/821546 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596049.
MLA Handbook (7th Edition):
Hayward, K L. “Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival.” 2014. Web. 04 Mar 2021.
Vancouver:
Hayward KL. Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival. [Internet] [Doctoral dissertation]. University of the West of England, Bristol; 2014. [cited 2021 Mar 04].
Available from: https://uwe-repository.worktribe.com/output/821546 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596049.
Council of Science Editors:
Hayward KL. Lipotoxicity and the role of translationally controlled tumour protein (TCTP) in pancreatic β-cell survival. [Doctoral Dissertation]. University of the West of England, Bristol; 2014. Available from: https://uwe-repository.worktribe.com/output/821546 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596049
University of Oxford
27.
Roworth, Alice Poppy.
Transcriptome-wide study of the role of arginine methylation on E2F1.
Degree: PhD, 2017, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:f1ab00c1-69a2-4d2f-a790-ba8f181cded3
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748912
► The transcription factor E2F1 can have diverse phenotypic effects on the cell, from stimulating cell cycle progression and proliferation, to inducing apoptosis. These seemingly opposite…
(more)
▼ The transcription factor E2F1 can have diverse phenotypic effects on the cell, from stimulating cell cycle progression and proliferation, to inducing apoptosis. These seemingly opposite effects are regulated by a multiplicity of post-translational modifications. Three sites of arginine methylation have been shown to cause a switch in E2F1 function, with PRMT5 mediated symmetric dimethylation at R111/113 associated with a proliferative outcome and asymmetric dimethylation at R109 by PRMT1 resulting in apoptosis. Importantly, these sites of arginine methylation by PRMT1 or PRMT5 were shown to be mutually exclusive, eliciting an either/or response. Furthermore, a reader for the R111/113Me2s mark was found to be the tudor-domain containing transcription co-activator and RNA binding protein p100-TSN. In this study we have used genome-wide sequencing techniques to explore the role of arginine methylation on E2F1 and identify how it is exerting these diverse effects. We found that, although there were few transcription level changes upon expression of an R111/113K mutant derivative compared to the wild-type expressing cells, these cells exhibited dramatic changes at the RNA isoform level across many E2F1 target genes, including increased levels of proapoptotic isoforms of p73 and BCL-X. Interestingly, the vast majority of these differentially spliced genes did not overlap with the genes showing transcription level changes, suggesting a new role for E2F1 to modulate target gene expression via RNA processing. Furthermore, we discovered that E2F1 can bind to nascent RNA via its interaction with p100-TSN and that this complex is spliceosome associated. Additionally, E2F1 can influence the RNA isoforms of p73 and BCL-X found interacting with p100-TSN. Thus, we present a model suggesting that E2F1 may be directly impacting on RNA processing by aiding assembly of splicing components as transcription occurs.
Subjects/Keywords: 572
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APA ·
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APA (6th Edition):
Roworth, A. P. (2017). Transcriptome-wide study of the role of arginine methylation on E2F1. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:f1ab00c1-69a2-4d2f-a790-ba8f181cded3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748912
Chicago Manual of Style (16th Edition):
Roworth, Alice Poppy. “Transcriptome-wide study of the role of arginine methylation on E2F1.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:f1ab00c1-69a2-4d2f-a790-ba8f181cded3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748912.
MLA Handbook (7th Edition):
Roworth, Alice Poppy. “Transcriptome-wide study of the role of arginine methylation on E2F1.” 2017. Web. 04 Mar 2021.
Vancouver:
Roworth AP. Transcriptome-wide study of the role of arginine methylation on E2F1. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:f1ab00c1-69a2-4d2f-a790-ba8f181cded3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748912.
Council of Science Editors:
Roworth AP. Transcriptome-wide study of the role of arginine methylation on E2F1. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:f1ab00c1-69a2-4d2f-a790-ba8f181cded3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748912
University of Oxford
28.
Lin, Chuhong.
Interfacial electrochemical kinetics.
Degree: PhD, 2017, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:03207db0-6625-4b20-9c10-ba69ee21d8c6
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748677
► The first two chapters in this thesis introduce the fundamental knowledge underpinning electrochemistry and numerical simulation. The rest of the thesis comprises three parts: investigation…
(more)
▼ The first two chapters in this thesis introduce the fundamental knowledge underpinning electrochemistry and numerical simulation. The rest of the thesis comprises three parts: investigation of charge transfer at the electrode-electrolyte interface; a kinetic study of electrocatalytic reactions at micro- and nano-electrodes; and the evaluation of electrochemical detection of single enzymes. In the first part the inner-sphere electron transfer is discussed under different situations where the breakage or formation of the chemical bond, the reorganization of the solvent and the influence of the electrical double layer are taken into consideration. Two important half-cell reactions in the field of fuel cells, the hydrogen oxidation reaction and the oxygen reduction reaction, are taken as examples and discussed in Chapter 3 and Chapter 4. The second part focuses primarily on the influence of the electrode size and geometry on electrocatalytic reactions. The kinetics reflecting both the mass transport of the reacting species and the electrocatalytic reaction are investigated. The application of simulation enables the measurement of the kinetic parameters and the determination of rate-determining factors in different experimental situations. The hydrogen oxidation reaction on nanoparticles is investigated in Chapter 5. Homogeneous and heterogeneous EC' (E: electrochemical step; C': catalytic step) reactions are discussed in Chapter 6, respectively. In the last section, the possible detection of single enzymes via the nano-impact electrochemical technique is explored in Chapter 7. The kinetics of the electrode system containing a freely-diffusing enzyme and a microelectrode is investigated and the experimental conditions required for the measurement of enzyme activity predicted.
Subjects/Keywords: 572
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APA (6th Edition):
Lin, C. (2017). Interfacial electrochemical kinetics. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:03207db0-6625-4b20-9c10-ba69ee21d8c6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748677
Chicago Manual of Style (16th Edition):
Lin, Chuhong. “Interfacial electrochemical kinetics.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:03207db0-6625-4b20-9c10-ba69ee21d8c6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748677.
MLA Handbook (7th Edition):
Lin, Chuhong. “Interfacial electrochemical kinetics.” 2017. Web. 04 Mar 2021.
Vancouver:
Lin C. Interfacial electrochemical kinetics. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:03207db0-6625-4b20-9c10-ba69ee21d8c6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748677.
Council of Science Editors:
Lin C. Interfacial electrochemical kinetics. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:03207db0-6625-4b20-9c10-ba69ee21d8c6 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748677
University of Oxford
29.
Hewitt, Dominic James.
Probing environmental effects on gas-phase protein structure.
Degree: PhD, 2017, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:6856e99f-c802-4b96-ba7c-8fc98456f6a0
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748793
► Growth in the use of mass spectrometry as an analytical tool for studying protein structure and functionality has posed questions regarding correlation of native structures…
(more)
▼ Growth in the use of mass spectrometry as an analytical tool for studying protein structure and functionality has posed questions regarding correlation of native structures and observed gas-phase conformations for proteins. This thesis explores the relationship between the solution-phase and gas-phase structures of soluble proteins, and investigates the effect of the lipid environment on membrane proteins. To assess gas-phase structure, ion-mobility mass spectrometry was used to measure directly the collision cross-sections of soluble proteins across a broad mass range. These collision cross-sections values were then compared with those derived from solution-phase data, calculated from dynamic light scattering experiments. Using computational methods collision cross-sections were calculated from structures reported in the protein data bank using a variety of techniques. Differing physical environments in solution and gas phases are not shown to affect protein structure by the dynamic light scattering and ion-mobility measurements. Contrastingly the computational calculations demonstrate that there is less correspondence between x-ray structures and their gas-phase counterparts. Despite the effect that lipid environment has on membrane protein structure, capturing this native environment has been challenging. Lipodisqs look to overcome this problem by removing the portion of the membrane surrounding the embedded protein. Lipodisqs were investigated as potential vehicles for membrane protein mass spectrometry and compared with conventional detergent based approaches. Lower charge states are observed for proteins released from lipodisqs, compared to those released from detergent micelles, increasing the probability of native features being retained including native-like protein-lipid interactions. Lipodisqs therefore demonstrate significant potential as a tool for membrane protein mass spectrometry. In summary, through this body of experimental work relationships have been established between gas-phase and solution-phase structures as well as computational methods. The use of Lipodisqs to eject membrane proteins from regions of the native membrane has been investigated.
Subjects/Keywords: 572
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Record Details
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
Hewitt, D. J. (2017). Probing environmental effects on gas-phase protein structure. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:6856e99f-c802-4b96-ba7c-8fc98456f6a0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748793
Chicago Manual of Style (16th Edition):
Hewitt, Dominic James. “Probing environmental effects on gas-phase protein structure.” 2017. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:6856e99f-c802-4b96-ba7c-8fc98456f6a0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748793.
MLA Handbook (7th Edition):
Hewitt, Dominic James. “Probing environmental effects on gas-phase protein structure.” 2017. Web. 04 Mar 2021.
Vancouver:
Hewitt DJ. Probing environmental effects on gas-phase protein structure. [Internet] [Doctoral dissertation]. University of Oxford; 2017. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:6856e99f-c802-4b96-ba7c-8fc98456f6a0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748793.
Council of Science Editors:
Hewitt DJ. Probing environmental effects on gas-phase protein structure. [Doctoral Dissertation]. University of Oxford; 2017. Available from: http://ora.ox.ac.uk/objects/uuid:6856e99f-c802-4b96-ba7c-8fc98456f6a0 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748793
University of Oxford
30.
Moustakim, Moses.
Discovery of small molecule epigenetic modulators.
Degree: PhD, 2018, University of Oxford
URL: http://ora.ox.ac.uk/objects/uuid:0d4a42f1-8a47-4ad5-ac30-b4eaf0d36db3
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748929
► Target validation is increasingly becoming a central tenet to successful execution of drug discovery campaigns. An emerging approach towards the development of novel therapies for…
(more)
▼ Target validation is increasingly becoming a central tenet to successful execution of drug discovery campaigns. An emerging approach towards the development of novel therapies for previously untreated diseases is the development of small molecule chemical probes which can be used as early stage tools for pertinent biological questions to be explored about a molecular target within the context of disease. A number of proteins which regulate epigenetic mechanisms have been correlated with disease onset and progression. Despite disease links, there remains a paucity in the understanding by which many of these pathologically relevant proteins exert their phenotypic effect when dysregulated. The discovery of novel chemical probes will facilitate further understanding of the underlying biology of these epigenetic targets. This thesis reports on the discovery and development of chemical probes and inhibitors of epigenetic proteins. A series of synthetic medicinal chemistry efforts is described towards the multiIfaceted improvements of lead compounds by means of potency, selectivity and cell activity against their cognate targets. In chapter 1 the associated concepts, primary literature and core principles of the subsequent chapters are comprehensively examined. In chapter 2 a report on the discovery of the first chemical probe for the bromodomains of p300/CBP Associated Factor (PCAF) and General Control Nonderepressible 5 (GCN5) proteins, previously untargeted and disease relevant protein domains is described. Following this, chapter 3 describes the development of inhibitors of the second macrodomain of polyadenosine diphosphate ribosylating protein 14 (PARP14) building on the understanding of SAR around the target and reporting the most potent ligand described to date. Chapter 4 then goes on to describe the discovery a chemical probe for the YEATS domain containing proteins ENL and Af9. Up to this date there have been no reported inhibitors or chemical probes for the YEATS domain containing proteins despite numerous links to cancers. The final chapter 5 describes the outputs from the industrial placement period of my doctoral training during which synthetic methodology and total synthesis research at Vertex Pharmaceuticals was carried out. In this chapter the substrate scope of an additive free UVIA promoted photocyclisation of arylI enamines to spiroindolines is described. The utility of this additiveIfree complexity building reaction is demonstrated through the formal synthesis of an alkaloid natural product (±)Ihorsfiline.
Subjects/Keywords: 572
Record Details
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Record Details
Similar Records
Cite
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Moustakim, M. (2018). Discovery of small molecule epigenetic modulators. (Doctoral Dissertation). University of Oxford. Retrieved from http://ora.ox.ac.uk/objects/uuid:0d4a42f1-8a47-4ad5-ac30-b4eaf0d36db3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748929
Chicago Manual of Style (16th Edition):
Moustakim, Moses. “Discovery of small molecule epigenetic modulators.” 2018. Doctoral Dissertation, University of Oxford. Accessed March 04, 2021.
http://ora.ox.ac.uk/objects/uuid:0d4a42f1-8a47-4ad5-ac30-b4eaf0d36db3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748929.
MLA Handbook (7th Edition):
Moustakim, Moses. “Discovery of small molecule epigenetic modulators.” 2018. Web. 04 Mar 2021.
Vancouver:
Moustakim M. Discovery of small molecule epigenetic modulators. [Internet] [Doctoral dissertation]. University of Oxford; 2018. [cited 2021 Mar 04].
Available from: http://ora.ox.ac.uk/objects/uuid:0d4a42f1-8a47-4ad5-ac30-b4eaf0d36db3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748929.
Council of Science Editors:
Moustakim M. Discovery of small molecule epigenetic modulators. [Doctoral Dissertation]. University of Oxford; 2018. Available from: http://ora.ox.ac.uk/objects/uuid:0d4a42f1-8a47-4ad5-ac30-b4eaf0d36db3 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.748929
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Open Access Theses and Dissertations
