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University of Manitoba
1.
Rivers, Damien M R.
Characterization of the Rhizobiaceae protein RhaK.
Degree: Microbiology, 2013, University of Manitoba
URL: http://hdl.handle.net/1993/30289 
► In Rhizobium leguminosarum the ABC transporter responsible for rhamnose transport is dependent on RhaK, a sugar kinase that is necessary for the catabolism of rhamnose.…
(more)
▼ In Rhizobium leguminosarum the
ABC transporter responsible for rhamnose transport is dependent on RhaK, a sugar kinase that is necessary for the catabolism of rhamnose. It was hypothesized that RhaK has two separate functions; phosphorylation of rhamnose, and an unknown interaction with the rhamnose
ABC transporter.
To address this hypothesis a linker-scanning mutagenesis of rhaK was carried out. Two generated variants (RhaK72 and RhaK73) were found to maintain kinase activity, but were severely impaired in rhamnose transport function. Structural modelling suggested that both RhaK72 and RhaK73 affect surface exposed residues in two distinct regions localized to one face of the protein. This suggests that this proteins face may play a role in a protein-protein interaction that affects rhamnose transport.
Using a two-hybrid system, an N-terminal and a C-teminal fragment of RhaK were both shown to interact with the N-terminal fragment of RhaT. These fragments span the regions that contain the rhaK73 and rhaK72 inserts respectively. When the rhaK72 and rhaK73 insert alleles were cloned and assayed using the two-hybrid system, these they were unable to interact with the RhaT fragment, suggesting these inserts abolish transport by interfering with a physical interaction between RhaT and RhaK.
A phylogeny was generated based on the amino acid sequence of RhaK like proteins found in syntenous opereons. To gain insight into what residues may constitute a binding domain a PRALINE alignment of the orthologous kinases was combined with secondary structure analysis, known informative mutations, and functional residue predictions. A putative 12 amino acid binding site was identified using this method. An alanine scanning mutagenesis and subsequent two-hybrid analysis was carried out on this region. The substitution of any of these residues greatly affected the interaction between RhaT and RhaK.
Although heterologous complementation of RhaK is possible, cosmid complementation anomalies and phylogenetic analysis of RhaK indicates the R. leguminosarum and S. meliloti kinases are different. Through a series of heterologous complementation experiments, enzyme assays, gene fusions, and transport experiments we show that the R. leguminosarum kinase is capable of directly phosphorylating rhamnose and rhamnulose, whereas the Sinorhizobium meliloti kinase does not have rhamnose kinase activity.
Advisors/Committee Members: Oresnik, Ivan (Microbiology) (supervisor), Court, Deborah (Microbiology) Cardona, Silvia (Microbiology) Stetefeld, Jorg (Chemistry) Finan, Turlough (McMaster University-Dept.of Biology) (examiningcommittee).
Subjects/Keywords: ABC transporter
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APA (6th Edition):
Rivers, D. M. R. (2013). Characterization of the Rhizobiaceae protein RhaK. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/30289
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rivers, Damien M R. “Characterization of the Rhizobiaceae protein RhaK.” 2013. Thesis, University of Manitoba. Accessed April 12, 2021.
http://hdl.handle.net/1993/30289.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rivers, Damien M R. “Characterization of the Rhizobiaceae protein RhaK.” 2013. Web. 12 Apr 2021.
Vancouver:
Rivers DMR. Characterization of the Rhizobiaceae protein RhaK. [Internet] [Thesis]. University of Manitoba; 2013. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/1993/30289.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rivers DMR. Characterization of the Rhizobiaceae protein RhaK. [Thesis]. University of Manitoba; 2013. Available from: http://hdl.handle.net/1993/30289
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Wake Forest University
2.
Liu, Mingxia.
ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM.
Degree: 2013, Wake Forest University
URL: http://hdl.handle.net/10339/39029
► Apolipoprotein M (ApoM) and ABCA1 are both expressed in hepatocytes, but their impact on lipid metabolism remains poorly defined. ApoM binds to plasma HDL via…
(more)
▼ Apolipoprotein M (ApoM) and ABCA1 are both expressed in hepatocytes, but their impact on lipid metabolism remains poorly defined. ApoM binds to plasma HDL via its retained signal peptide and transports sphingosine 1–phosphate (S1P). We found that liver–specific apoM transgenic mice had larger plasma HDLs enriched with apoM, cholesteryl ester, lecithin:cholesterol acyltransferase and S1P, but not enhanced macrophage reverse cholesterol transport compared to wild type mice. Hepatocytes from transgenic mice generated larger nascent HDLs and stimulated sphingolipid synthesis and S1P secretion. Inhibition of ceramide synthase significantly increased cellular but not media S1P in apoM Tg hepatocytes, suggesting that apoM is rate limiting for S1P secretion. Overexpression of apoMQ22A, a mutant form of apoM with a cleavable signal peptide, in HEK293 cells and in mice did not stimulate larger nascent or mature HDL formation, but its overexpression in hepatocytes had faster secretion of apoMQ22A and mobilization of cellular S1P than apoMWT. We conclude that hepatic apoM overexpression facilitates the generation of large, apoM/S1P–enriched plasma HDLs and that this activity is dependent on its signal peptide retention.
Subjects/Keywords: ABC transporter A1
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APA (6th Edition):
Liu, M. (2013). ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM. (Thesis). Wake Forest University. Retrieved from http://hdl.handle.net/10339/39029
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Liu, Mingxia. “ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM.” 2013. Thesis, Wake Forest University. Accessed April 12, 2021.
http://hdl.handle.net/10339/39029.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Liu, Mingxia. “ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM.” 2013. Web. 12 Apr 2021.
Vancouver:
Liu M. ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM. [Internet] [Thesis]. Wake Forest University; 2013. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/10339/39029.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Liu M. ROLE OF HEPATIC APOLIPOPROTEIN M AND ATP-BINDING CASSETTE TRANSPORTER A1 (ABCA1) IN LIPID METABOLISM. [Thesis]. Wake Forest University; 2013. Available from: http://hdl.handle.net/10339/39029
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
3.
Hicks, Dennis.
NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter.
Degree: MSin Chemistry, Chemistry, 2019, University of San Francisco
URL: https://repository.usfca.edu/thes/1204
► ATP-Binding Cassette (ABC) Transporters are a superfamily of integral membrane proteins that have been found embedded in both the cellular membranes and internal organelles…
(more)
▼ ATP-Binding Cassette (
ABC) Transporters are a superfamily of integral membrane proteins that have been found embedded in both the cellular membranes and internal organelles of all species yet analyzed (1). This extreme conservation throughout the tree of life is due to their vitally critical and broad task of transporting all manner of things into and out of the cell and related organelles. This broadness of responsibility has led to an abundant diversity of this family, which in turn, has allowed life to adapt to the many environments found on Earth. While the importance and variability of this family is abundantly clear, many mechanistic and regulatory questions remain. The diversity which has made this family so useful in the natural world has resulted in a huge challenge in the scientific world: elucidating the many mechanisms this family has developed to perform its many functions.
The scientific community has so far been able to identify overarching features of all
ABC transporters such as the Walker A and Walker B motifs (1); however, the mechanisms of individual transporters remain undiscovered. In my research, I focus on a specific
ABC transporter called NaAtm1 (
Novosphingobium aromaticivorans ABC transporter of mitochondria 1), which has been shown to mediate transition metal export in its host species (2). While some transition metals (e.g. iron and copper) are essential for certain cellular processes such as respiration and enzyme catalysis, other metals (e.g. cadmium and mercury) can be very toxic. Due to this extreme dichotomy, a cell’s ability to distinguish between friend and foe is of the utmost importance, and therefore is a highly regulated process.
My goal during this program was to purify NaAtm1 and create a realistic in-vitro environment to analyze and better understand the full mechanism of this
transporter, to determine why it exports some metals while leaving others alone, and to understand the regulatory processes that control it.
<h3> </h3>
<h3> </h3>
<h3> </h3>
<h3> </h3>
<h3>References</h3>
[1] Davidson, A. L.; Dassa, E.; Orelle, C.; Chen, J. Structure, function, and evolution of bacterial ATP-binding cassette systems.
Microbiology and Molecular Biology Reviews 2008,
72(2), 317–364.
[2] Lee, J. Y.; Yang, J. G.; Zhitnitsky, D.; Lewinson, O.; Rees, D. C. Structural basis for heavy metal detoxification by an Atm1-type
ABC exporter.
Science 2014,
343(6175), 1133–11
Advisors/Committee Members: Dr. Janet Yang, Dr. Ryan West, Dr. Nicole Thometz.
Subjects/Keywords: ABC-Transporter; Biochemistry
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APA (6th Edition):
Hicks, D. (2019). NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter. (Thesis). University of San Francisco. Retrieved from https://repository.usfca.edu/thes/1204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hicks, Dennis. “NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter.” 2019. Thesis, University of San Francisco. Accessed April 12, 2021.
https://repository.usfca.edu/thes/1204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hicks, Dennis. “NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter.” 2019. Web. 12 Apr 2021.
Vancouver:
Hicks D. NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter. [Internet] [Thesis]. University of San Francisco; 2019. [cited 2021 Apr 12].
Available from: https://repository.usfca.edu/thes/1204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hicks D. NaAtm1: Examining the mechanism of a Heavy-metal ABC Exporter. [Thesis]. University of San Francisco; 2019. Available from: https://repository.usfca.edu/thes/1204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Tokyo Institute of Technology / 東京工業大学
4.
Hsu, Wei-Lin.
Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations.
Degree: 博士（工学）, 2016, Tokyo Institute of Technology / 東京工業大学
URL: http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100711995
► ATP-binding cassette (ABC) transporters are able to translocate various substrates across cell membranes, and thus considered clinically important. However, the detailed translocation mechanism still remains…
(more)
▼ ATP-binding cassette (ABC) transporters are able to translocate various substrates across cell membranes, and thus considered clinically important. However, the detailed translocation mechanism still remains elusive. In this study, we focused upon the maltose transporter from E. coli to explore this issue. I first performed conventional all-atom molecular dynamics (cMD) and accelerated molecular dynamics (aMD) simulations on MalK2, the subunits that include the nucleotide-binding domains, and elucidated the relationship between the conformational change and the binding of Mg-ATP. Next, we performed cMD for the full transporter consisting of MalK2, MalFG and MalE domains, and found that the binding of MalE plays an important role in inducing the whole structural transformation. Finally, using QM/MM metadynamics simulation, we elucidated the ATP hydrolysis mechanism from viewpoints of free energy path and its related proton transfers. As the molecular architecture is highly conserved among all ABC transporters, these results would be applicable to elucidate the functional mechanisms of other members of the ABC transporters.
Subjects/Keywords: ABC transporter; metadynamics; maltose transporter; aMD
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APA (6th Edition):
Hsu, W. (2016). Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations. (Thesis). Tokyo Institute of Technology / 東京工業大学. Retrieved from http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100711995
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hsu, Wei-Lin. “Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations.” 2016. Thesis, Tokyo Institute of Technology / 東京工業大学. Accessed April 12, 2021.
http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100711995.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hsu, Wei-Lin. “Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations.” 2016. Web. 12 Apr 2021.
Vancouver:
Hsu W. Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations. [Internet] [Thesis]. Tokyo Institute of Technology / 東京工業大学; 2016. [cited 2021 Apr 12].
Available from: http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100711995.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hsu W. Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations : Elucidation of functionally important dynamics and structural changes of the E. coli maltose transporter by all-atom molecular dynamics simulations. [Thesis]. Tokyo Institute of Technology / 東京工業大学; 2016. Available from: http://t2r2.star.titech.ac.jp/cgi-bin/publicationinfo.cgi?q_publication_content_number=CTT100711995
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Ruhr Universität Bochum
5.
Uhlenbrock, Guido.
Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster.
Degree: 2011, Ruhr Universität Bochum
URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31436
► DVMAT-B als vesikulärer Monoamintransporter konnte überraschenderweise, eindeutig in der Fensterglia der Lamina lokalisiert werden und nicht in Neuronen. Zudem hat DVMAT-B einen Einfluss auf das…
(more)
▼ DVMAT-B als vesikulärer Monoamintransporter konnte
überraschenderweise, eindeutig in der Fensterglia der Lamina
lokalisiert werden und nicht in Neuronen. Zudem hat DVMAT-B einen
Einfluss auf das phototaktische Verhalten der Fliegen und sein
Fehlen erzeugt schwache Defekte im ERG. Weiterhin weisen
dVMAT-Mutanten einen geringeren Histamingehalt im Kopf auf. Dies
zeigt den Einfluss von DVMAT-B auf die Histaminhomöostase. Der
putative
Transporter Inebriated (Ine) konnte ebenfalls
ausschließlich in Gliazellen identifiziert werden. Eine neuronale
Expression im visuellen System von Drosophila melanogaster ist
weitestgehend ausgeschlossen. Ine-P1 ist in der Fensterglia und der
distalen Satellitenglia lokalisiert. Ine-P2 wird in der
Pseudocartridgeglia und der proximalen Satellitenglia exprimert.
Optomotorische Verhaltensexperimente zeigten, dass diese Proteine
eine Wirkung auf das visuelle System von Drosophila aufweisen.
Zudem weisen ine-Mutanten eine erhöhte Histaminkonzentration im
Kopf auf.
Advisors/Committee Members: Chemie.
Subjects/Keywords: Histamin; ABC-Transporter; Drosophila;
Neurotransmitter; Synapse
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APA ·
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APA (6th Edition):
Uhlenbrock, G. (2011). Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31436
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Uhlenbrock, Guido. “Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster.” 2011. Thesis, Ruhr Universität Bochum. Accessed April 12, 2021.
http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31436.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Uhlenbrock, Guido. “Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster.” 2011. Web. 12 Apr 2021.
Vancouver:
Uhlenbrock G. Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster. [Internet] [Thesis]. Ruhr Universität Bochum; 2011. [cited 2021 Apr 12].
Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31436.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Uhlenbrock G. Identifizierung und Charakterisierung von
Histamintransportern im visuellen System von Drosophila
melanogaster. [Thesis]. Ruhr Universität Bochum; 2011. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-31436
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Ruhr Universität Bochum
6.
Radtke, Debbie.
Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice.
Degree: 2012, Ruhr Universität Bochum
URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-38451
► In der vorliegenden Arbeit konnte gezeigt werden, dass trigeminale Ganglienneurone (TGNs), im Gegensatz zu den meisten zentralen Neuronen, auch postnatal eine hohe intrazelluläre Chloridkonzentration vorweisen.…
(more)
▼ In der vorliegenden Arbeit konnte gezeigt werden,
dass trigeminale Ganglienneurone (TGNs), im Gegensatz zu den
meisten zentralen Neuronen, auch postnatal eine hohe intrazelluläre
Chloridkonzentration vorweisen. Die intrazelluläre Akkumulation von
Chlorid wird hauptsächlich durch den Na+-K+-2Cl- Cotransporter
NKCC1 gewährleistet. Auf Grund der hohen intrazellulären
Chloridkonzentration führt das Öffnen von Chlorid-leitenden GABAA
Rezeptoren nicht zu einem Einstrom von Chlorid-Ionen sondern zu
einem depolarisierenden Ausstrom. Außerdem ist dies die erste
Studie, die eine Capsaizin-induzierte Signalverstärkung durch
Kalzium-aktivierte Chloridkanäle nachweist. Außerdem befasst sich
diese Arbeit mit der Rolle des trigeminalen sensorischen Systems
bei der Wahrnehmung von Adstringenz. Es konnte gezeigt werden, dass
verschiedene adstringierende Substanzen, die alle eine
Galloylgruppe vorweisen, in der Lage sind, TGNs in Kalzium-Imaging
Experimenten zu aktivieren.
Advisors/Committee Members: Biologie.
Subjects/Keywords: Chloridion; Trigeminus; Schmerz; Sensorik
(Neurophsiologie); ABC-Transporter
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APA ·
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Manager
APA (6th Edition):
Radtke, D. (2012). Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-38451
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Radtke, Debbie. “Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice.” 2012. Thesis, Ruhr Universität Bochum. Accessed April 12, 2021.
http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-38451.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Radtke, Debbie. “Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice.” 2012. Web. 12 Apr 2021.
Vancouver:
Radtke D. Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice. [Internet] [Thesis]. Ruhr Universität Bochum; 2012. [cited 2021 Apr 12].
Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-38451.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Radtke D. Chloride homeostasis and chemoreception in trigeminal
sensory neurons of mice. [Thesis]. Ruhr Universität Bochum; 2012. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-38451
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
7.
Smart, Eleanor.
From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia.
Degree: 2020, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:323439
► Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of cancer treatment. Despite this, there are currently no pharmacological interventions available and there…
(more)
▼ Chemotherapy-induced alopecia (CIA) is one of the
most distressing side effects of cancer treatment. Despite this,
there are currently no pharmacological interventions available and
there is therefore an urgent need to identify new targets for
therapy. It has been previously hypothesised that increasing drug
transport out of the hair follicle (HF) could render human scalp
HFs resistant to chemotherapy. Recently, it was demonstrated that
human scalp HFs express many different members of the ATP-binding
cassette (
ABC) superfamily, which efflux a wide variety of
chemotherapeutic agents from diverse cell types. However, their
role in mediating HF resistance to chemotherapy remains
unexplored.The primary aim of this study was to investigate the
role of
ABC transporter expression and activity in the HF as a
novel mechanism for protecting against chemotherapy-induced damage
and subsequent hair loss.Firstly, this study showed that inhibition
of ABCB1 in human HFs ex vivo sensitizes HFs to damage by both
4-hydroxycyclophosphamide (4HC) and Doxorubicin (DOX). Not only
does this study indicate that ABCB1 has a role in protecting the
human HF from chemotherapy-induced damage, but it also adds to the
growing indirect evidence that 4HC is a substrate of ABCB1. Next,
outer root sheath (ORS) keratinocytes were examined as a
HF-relevant primary cell model to screen for
ABC transporter
inducing compounds. T0901317 (a LXR agonist), lopinavir (a protease
inhibitor) and dexamethasone (a glucocorticoid receptor agonist),
increased
ABC transporter activity, significantly increased cell
survival and attenuated apoptosis on exposure to DOX. T0901317, but
not lopinavir, showed a trend towards protection of human HFs ex
vivo from DOX-induced apoptosis. However, the protective effect of
T0901317 could not be modified by inhibition of
ABC transporter
activity, which indicated an
ABC-independent mechanism of
protection. Therefore, the mechanism of protection of ORS
keratinocytes from DOX was investigated by RNA-sequencing. It was
found that T0901317 exerted protection in a multifaceted manner,
including the modulation of fatty acid synthesis, DNA repair and
key signalling pathway modulation (NFκB and MAPK). This study
showed that despite ABCB1 modulating chemotherapy-induced damage to
the human HF, its transcription could not be significantly
increased in culture. However, the LXR agonist T0901317 protected
primary ORS keratinocytes and human HFs ex vivo from DOX-induced
toxicity, through the modulation of DNA double strand break repair
and fatty acid synthesis.
Advisors/Committee Members: HASLAM, IAIN IS, Paus, Ralf, Haslam, Iain.
Subjects/Keywords: Hair follicle; ABC transporter; Chemotherapy; Alopecia
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Manager
APA (6th Edition):
Smart, E. (2020). From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:323439
Chicago Manual of Style (16th Edition):
Smart, Eleanor. “From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia.” 2020. Doctoral Dissertation, University of Manchester. Accessed April 12, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:323439.
MLA Handbook (7th Edition):
Smart, Eleanor. “From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia.” 2020. Web. 12 Apr 2021.
Vancouver:
Smart E. From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia. [Internet] [Doctoral dissertation]. University of Manchester; 2020. [cited 2021 Apr 12].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:323439.
Council of Science Editors:
Smart E. From Drug Efflux to the Liver X Receptor: Investigations
into Novel Methods to Protect Against Chemotherapy-Induced
Alopecia. [Doctoral Dissertation]. University of Manchester; 2020. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:323439
University of California – San Francisco
8.
Friedman, Jessica Lauren.
Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity.
Degree: Pharmaceutical Sciences and Pharmacogenomics, 2015, University of California – San Francisco
URL: http://www.escholarship.org/uc/item/7xv9f7fb
► ATP-binding cassette (ABC) transporters are a diverse family of transmembrane proteins that facilitate the ATP powered translocation of substrates across cellular membranes. Multidrug resistance-associated protein…
(more)
▼ ATP-binding cassette (ABC) transporters are a diverse family of transmembrane proteins that facilitate the ATP powered translocation of substrates across cellular membranes. Multidrug resistance-associated protein 4 (MRP4) is a highly polymorphic, human ABC transporter with a wide array of substrates, including, antiviral drugs and prostaglandins. Previously, altered antiviral drug transport capacities of nonsynonymous single nucleotide polymorphic MRP4 variants, relative to reference MRP4 transport activity, were reported. This project focused on characterizing the ATP hydrolysis capabilities of the G487E MRP4 variant (rs11568668); G487 is located in an ATP binding cassette, also known as the nucleotide binding domain, of MRP4. Previously published works report a 0.008 minor allele frequency in Asian American individuals (n = 120) and show decreased transport activity with G487E. Novel data on G487E MRP4 activity from this study corroborate the decreased drug transport findings. This study characterized prostaglandin E2 – stimulated ATP hydrolysis by human MRP4 reference and G487E variant expressed in insect cells. MRP4 specific activity was determined by its selective inhibition with beryllium fluoride. Reference MRP4 reached a maximal ATP hydrolysis velocity of 27.4 +/- 1.07 nmoles Pi/mg protein/minute; for comparison, ATP hydrolysis in Sf21 membranes absent of exogenous transporters reached a maximum velocity of 18.4 +/- 0.55 nmoles Pi/mg protein/minute. The G487E MRP4 variant had an intermediate Vmax value of 24.4 +/- 0.93 nmoles Pi/mg protein/minute. As measured by an ANOVA, Vmax values for the Sf21, MRP4 reference and G487E MRP4 membranes were significantly different (p < 0.0001). In contrast, Km values were similar for the three sample types and ranged from 0.34 +/- 0.16 µM for reference MRP4 to 0.44 +/- 0.18 µM for G487E MRP4. Structural rationales for these data were explored using novel homology models of the first nucleotide binding domain of MRP4. The G487E mutation was determined to only affect the MRP4 binding affinity of ATP; prostaglandin E2 binding was not impacted. These results suggest that the reduced transport phenotype of G487E MRP4 relative to reference MRP4 is due, at least in part, to impaired ATP hydrolysis.
Subjects/Keywords: Pharmaceutical sciences; Biochemistry; ABC transporter; MRP4
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APA (6th Edition):
Friedman, J. L. (2015). Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/7xv9f7fb
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Friedman, Jessica Lauren. “Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity.” 2015. Thesis, University of California – San Francisco. Accessed April 12, 2021.
http://www.escholarship.org/uc/item/7xv9f7fb.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Friedman, Jessica Lauren. “Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity.” 2015. Web. 12 Apr 2021.
Vancouver:
Friedman JL. Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity. [Internet] [Thesis]. University of California – San Francisco; 2015. [cited 2021 Apr 12].
Available from: http://www.escholarship.org/uc/item/7xv9f7fb.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Friedman JL. Effect of ABCC4 Genetic Variation on MRP4 ATPase Activity. [Thesis]. University of California – San Francisco; 2015. Available from: http://www.escholarship.org/uc/item/7xv9f7fb
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
9.
Smart, Eleanor.
From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia.
Degree: PhD, 2020, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/from-drug-efflux-to-the-liver-x-receptor-investigations-into-novel-methods-to-protect-against-chemotherapyinduced-alopecia(f7ee1491-5c83-48bb-9c2c-4cebcb9d11da).html
;
https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799479
► Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of cancer treatment. Despite this, there are currently no pharmacological interventions available and there…
(more)
▼ Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of cancer treatment. Despite this, there are currently no pharmacological interventions available and there is therefore an urgent need to identify new targets for therapy. It has been previously hypothesised that increasing drug transport out of the hair follicle (HF) could render human scalp HFs resistant to chemotherapy. Recently, it was demonstrated that human scalp HFs express many different members of the ATP-binding cassette (ABC) superfamily, which efflux a wide variety of chemotherapeutic agents from diverse cell types. However, their role in mediating HF resistance to chemotherapy remains unexplored. The primary aim of this study was to investigate the role of ABC transporter expression and activity in the HF as a novel mechanism for protecting against chemotherapy-induced damage and subsequent hair loss. Firstly, this study showed that inhibition of ABCB1 in human HFs ex vivo sensitizes HFs to damage by both 4-hydroxycyclophosphamide (4HC) and Doxorubicin (DOX). Not only does this study indicate that ABCB1 has a role in protecting the human HF from chemotherapy-induced damage, but it also adds to the growing indirect evidence that 4HC is a substrate of ABCB1. Next, outer root sheath (ORS) keratinocytes were examined as a HF-relevant primary cell model to screen for ABC transporter inducing compounds. T0901317 (a LXR agonist), lopinavir (a protease inhibitor) and dexamethasone (a glucocorticoid receptor agonist), increased ABC transporter activity, significantly increased cell survival and attenuated apoptosis on exposure to DOX. T0901317, but not lopinavir, showed a trend towards protection of human HFs ex vivo from DOX-induced apoptosis. However, the protective effect of T0901317 could not be modified by inhibition of ABC transporter activity, which indicated an ABC-independent mechanism of protection. Therefore, the mechanism of protection of ORS keratinocytes from DOX was investigated by RNA-sequencing. It was found that T0901317 exerted protection in a multifaceted manner, including the modulation of fatty acid synthesis, DNA repair and key signalling pathway modulation (NFκB and MAPK). This study showed that despite ABCB1 modulating chemotherapy-induced damage to the human HF, its transcription could not be significantly increased in culture. However, the LXR agonist T0901317 protected primary ORS keratinocytes and human HFs ex vivo from DOX-induced toxicity, through the modulation of DNA double strand break repair and fatty acid synthesis.
Subjects/Keywords: ABC transporter; Hair follicle; Chemotherapy; Alopecia
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Smart, E. (2020). From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/from-drug-efflux-to-the-liver-x-receptor-investigations-into-novel-methods-to-protect-against-chemotherapyinduced-alopecia(f7ee1491-5c83-48bb-9c2c-4cebcb9d11da).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799479
Chicago Manual of Style (16th Edition):
Smart, Eleanor. “From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia.” 2020. Doctoral Dissertation, University of Manchester. Accessed April 12, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/from-drug-efflux-to-the-liver-x-receptor-investigations-into-novel-methods-to-protect-against-chemotherapyinduced-alopecia(f7ee1491-5c83-48bb-9c2c-4cebcb9d11da).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799479.
MLA Handbook (7th Edition):
Smart, Eleanor. “From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia.” 2020. Web. 12 Apr 2021.
Vancouver:
Smart E. From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia. [Internet] [Doctoral dissertation]. University of Manchester; 2020. [cited 2021 Apr 12].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/from-drug-efflux-to-the-liver-x-receptor-investigations-into-novel-methods-to-protect-against-chemotherapyinduced-alopecia(f7ee1491-5c83-48bb-9c2c-4cebcb9d11da).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799479.
Council of Science Editors:
Smart E. From drug efflux to the liver X receptor : investigations into novel methods to protect against chemotherapy-induced alopecia. [Doctoral Dissertation]. University of Manchester; 2020. Available from: https://www.research.manchester.ac.uk/portal/en/theses/from-drug-efflux-to-the-liver-x-receptor-investigations-into-novel-methods-to-protect-against-chemotherapyinduced-alopecia(f7ee1491-5c83-48bb-9c2c-4cebcb9d11da).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.799479
University of Sydney
10.
Mohd Noor, Siti Nurfadhlina.
Characterization of transport proteins on the symbiosome membrane of Glycine max
.
Degree: 2016, University of Sydney
URL: http://hdl.handle.net/2123/16500
► During the legume-rhizobia symbiosis, a new plant organ called the root nodule is induced and developed. Within the root nodule, rhizobia are enclosed in the…
(more)
▼ During the legume-rhizobia symbiosis, a new plant organ called the root nodule is induced and developed. Within the root nodule, rhizobia are enclosed in the symbiosome. The symbiosome is an organelle where rhizobia fix atmospheric nitrogen and is surrounded by the plant-derived symbiosome membrane (SM). The SM regulates nutrient exchange between the symbionts, and thus effectively controls the symbiosis. GmABCA1 and GmABCA2 proteins have been identified by proteomic analysis on the SM of soybean. These proteins are part of the large ATP-binding cassette (ABC) superfamily that transports diverse substrates and plays essential roles in plant growth and development. The present work aims to characterize GmABCA1 and GmABCA2, and to explore potential function they may play in relation to fatty acid transport. Expression analyses showed that they are preferentially expressed in the nodule tissue, and have specific expression in infected cells. The localization of GmABCA2 on the SM was confirmed by FP tagging but that of GmABCA1 could not be determined by this method. Complementation of the yeast fatty acid uptake-deficient mutant, Δfat1, indicated that both proteins were able to transport oleic acid. They also complemented the T-DNA mutant for the Arabidopsis fatty acid transporter Atabca9. The nitrate transporter 1/peptide transporter family (NPF) is mainly involved in the transport of nitrates and peptides in plants. Complementation of eight soybean NPF members with enhanced expression in nodule: GmNPF1.2, GmNPF5.24, GmNPF5.25, GmNPF5.29, GmNPF5.30, GmNPF5.2, GmNPF5.3 and GmNPF8.6 in a yeast peptide transport mutant, ptr2, was attempted in this study. Only GmNPF8.6 was able to restore ptr2 yeast growth on minimal media containing tri-alanine, glycine-proline and valine-leucine peptides as the sole source of nitrogen. This study provides the first evidence of such transport across the SM.
Subjects/Keywords: soybean;
symbiosome membrane;
ABC;
NPF;
transporter
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mohd Noor, S. N. (2016). Characterization of transport proteins on the symbiosome membrane of Glycine max
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/16500
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mohd Noor, Siti Nurfadhlina. “Characterization of transport proteins on the symbiosome membrane of Glycine max
.” 2016. Thesis, University of Sydney. Accessed April 12, 2021.
http://hdl.handle.net/2123/16500.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mohd Noor, Siti Nurfadhlina. “Characterization of transport proteins on the symbiosome membrane of Glycine max
.” 2016. Web. 12 Apr 2021.
Vancouver:
Mohd Noor SN. Characterization of transport proteins on the symbiosome membrane of Glycine max
. [Internet] [Thesis]. University of Sydney; 2016. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/2123/16500.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mohd Noor SN. Characterization of transport proteins on the symbiosome membrane of Glycine max
. [Thesis]. University of Sydney; 2016. Available from: http://hdl.handle.net/2123/16500
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manitoba
11.
Kim, Derek Dohyun.
Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum.
Degree: Microbiology, 2019, University of Manitoba
URL: http://hdl.handle.net/1993/34396
► ATP-binding cassette (ABC) transporters are found throughout all domains of life. Sugar importers are often categorized under the Carbohydrate Uptake Transporter (CUT) system. This classification…
(more)
▼ ATP-binding cassette (
ABC) transporters are found throughout all domains of life. Sugar importers are often categorized under the Carbohydrate Uptake
Transporter (CUT) system. This classification system is based on the structure of the
ABC, in which CUT1 ABCs are comprised of a dimer of two peptides and CUT2s are believed to consist of a single protein. A novel
ABC transporter interaction was previously discovered in Rhizobium leguminosarum. The transport activity of the L-rhamnose importer was found to be dependent on an interaction between the sugar kinase (RhaK) and a CUT2
ABC protein (RhaT). In this work, a partial rhaT deletion mutant was found to retain the ability to grow on rhamnose as a sole carbon source, despite missing a substantial portion of its internal region. Through in silico approaches, this partial deletion was characterized and two rhaT truncation mutants were designed to truncate a CUT2
ABC to resemble a CUT1. Although transport rates were greatly reduced, these truncation mutants were able to preserve growth, supporting the feasibility of converting a CUT2
transporter to CUT1. In addition, rhaT deletions were unable to be complemented by rhaT as an independent gene in trans. Complementation of this gene using a multigene transcript was found as a potential workaround to complement this membrane protein. These findings will likely help steer towards characterizing RhaT in the context of its interaction with the kinase RhaK.
Advisors/Committee Members: Oresnik, Ivan (Microbiology) (supervisor), Court, Deborah (Microbiology) (examiningcommittee), Sparling, Richard (Microbiology) (examiningcommittee).
Subjects/Keywords: ABC transporter; Rhizobium; Microbiology; Carbohydrate Uptake Transporter; Rhamnose
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, D. D. (2019). Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/34396
Chicago Manual of Style (16th Edition):
Kim, Derek Dohyun. “Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum.” 2019. Masters Thesis, University of Manitoba. Accessed April 12, 2021.
http://hdl.handle.net/1993/34396.
MLA Handbook (7th Edition):
Kim, Derek Dohyun. “Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum.” 2019. Web. 12 Apr 2021.
Vancouver:
Kim DD. Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum. [Internet] [Masters thesis]. University of Manitoba; 2019. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/1993/34396.
Council of Science Editors:
Kim DD. Toward the characterization of the ATP-binding cassette protein RhaT in Rhizobium leguminosarum. [Masters Thesis]. University of Manitoba; 2019. Available from: http://hdl.handle.net/1993/34396
Texas Tech University
12.
Swartz, Douglas.
Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism.
Degree: TTUHSC – Biochemistry and Molecular Genetics, 2012, Texas Tech University
URL: http://hdl.handle.net/2346/47087
► P-glycoprotein (Pgp) is an ATP Binding Cassette (ABC) transporter that functions as a multidrug efflux pump, and contributes to multidrug resistance in cancer and other…
(more)
▼ P-glycoprotein (Pgp) is an ATP Binding Cassette (
ABC)
transporter that functions as a multidrug efflux pump, and contributes to multidrug resistance in
cancer and other diseases. Pgp operates through a poorly understood ATP dependent polyspecific transport mechanism that allows it to bind and transport
a wide variety of structurally unrelated drugs. Understanding Pgp drug binding and transport would allow rational design of novel Pgp inhibitors and
provide a better understanding of the general
ABC transport mechanism. In this work, Pgp was genetically modified to build two new tools for
biophysical studies: a tryptophan (Trp)-less Pgp that can be used for site-specific Trp fluorescence studies of Pgp drug binding sites, and a cysteine
(Cys)-less Pgp that can be labeled with spectroscopic probes for measuring the intramolecular distances needed to identify distinct Pgp protein
conformations. Initial efforts to replace the eleven endogenous Pgp Trps with another aromatic amino acid demonstrated that multiple Trps could be
removed from Pgp while maintaining protein function, but also suggested that aromatic residues are not always the best Trp replacements. Therefore, a
directed evolution procedure was developed to determine which amino acids could replace each endogenous Pgp Trp. Site-saturation mutagenesis
simultaneously replaced blocks of 3 or 4 Pgp Trps with the 19 other amino acids. The mutants were subjected to a stringent selection in yeast to
determine which amino acids could replace each Trp. These mutants were then combined into full-length Pgp Trp mutants and re-selected. This approach
successfully identified several Trp-less and minimal Trp Pgp mutants, which contain one or two native Trps in positions suitable for drug binding studies.
Similarly, directed evolution was used to remove Cys residues from a codon optimized Pgp gene that was previously designed and characterized.
Directed evolution revealed that the preferred amino acid substitutions were location specific and generally biased towards non-conserved amino acids
such as glycine and proline. While this work successfully produced two new tools for studying Pgp, it also demonstrates that removing conserved amino
acids, such as Trp and Cys, from a protein is highly dependent on the local environment of the residue being replaced.
Advisors/Committee Members: Urbatsch, Ina L. (Committee Chair), Faust, Charles (committee member), Hardy, Daniel (committee member), MacDonald, Clinton C. (committee member), Weber, Joachim (committee member).
Subjects/Keywords: P-gloycoprotein; Membrane protein; ATP binding cassette (ABC) transporter; Multidrug transporter
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Swartz, D. (2012). Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism. (Thesis). Texas Tech University. Retrieved from http://hdl.handle.net/2346/47087
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Swartz, Douglas. “Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism.” 2012. Thesis, Texas Tech University. Accessed April 12, 2021.
http://hdl.handle.net/2346/47087.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Swartz, Douglas. “Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism.” 2012. Web. 12 Apr 2021.
Vancouver:
Swartz D. Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism. [Internet] [Thesis]. Texas Tech University; 2012. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/2346/47087.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Swartz D. Genetic manipulation of P-glycoprotein provides new tools for biophysical studies of the ABC multidrug transport mechanism. [Thesis]. Texas Tech University; 2012. Available from: http://hdl.handle.net/2346/47087
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Helsinki
13.
Cai, Yida.
Secretion of bacteriocins in Leuconostoc carnosum 4010.
Degree: Department of Food and Environmental Sciences; Helsingfors universitet, Agrikultur- och forstvetenskapliga fakulteten, Institutionen för livsmedels- och miljövetenskaper, 2018, University of Helsinki
URL: http://hdl.handle.net/10138/236075
► Bacteriocins are ribosomally synthesized antimicrobial proteins. They can be applied as biopreservatives in food processing for extending the shelf-life of food. Lactic acid bacterium Leuconostoc…
(more)
▼ Bacteriocins are ribosomally synthesized antimicrobial proteins. They can be applied as biopreservatives in food processing for extending the shelf-life of food. Lactic acid bacterium Leuconostoc carnosum 4010 is Generally Recognized As Safe strain, which can be used as a protective culture in meat products. The strain 4010 produces three bacteriocins: leucocins A (LcnA), B (LebB) and C (LecC). For the secretion of bacteriocin out from the cell, bacteria usually use an ABC transporter, which is often dedicated to secrete only one bacteriocin. The leucocin operons in Ln. carnosum 4010 plasmids include genes for only one ABC transporter, namely LecXTS. The fact that Ln. carnosum 4010 produces three bacteriocins but only carries one bacteriocin transporter, raises a question, which leucocin(s) is/are translocated via LecXTS transporter. Therefore, the first aim of this study was to determine which bacteriocin(s) is/are secreted by LecXTS in Ln. carnosum 4010.
Ln. carnosum 4010 carries at least two plasmids. Leucocin A gene lcnA is located on the plasmid pLC4010-2, and leucocin B and C with transporter genes (lebB, lecC, lecXTS) are located on the plasmid pLC4010-1. In a previous work, two plasmid cured derivatives of Ln. carnosum 4010 have been made: the plasmid-free strain PCS-10, and the strain PCS-11 carrying only pLC4010-2. Neither of the derivatives secrete bacteriocins. In this study, the idea was to construct five recombinant plasmids containing the pLC4010-1 replication gene repB and a gene for erythromycin resistance ErmR. They were ligated with different sets of leucocin and transporter genes (repB-lebB-lecXTS-lecC-ErmR, repB-lebB-lecXTS-ErmR, repB-lebB-ErmR, repB-lecC-ErmR, and a vector control with only repB-ErmR). The constructs were aimed to be introduced into the two Ln. carnosum 4010 mutant strains PCS-10 and PCS-11. However, after several attempts of electroporation, no colonies were obtained. To acquire a testing plasmid for optimization of transformation, the ligation mixture for the smallest plasmid repB-ErmR was electroporated into another strain, Lactococcus lactis N8. The plasmid repB-ErmR was successfully obtained from Lc. lactis N8. For improving the efficiency of transformation, the plasmid repB-ErmR was isolated from Lc. lactis N8, and the plasmid was used in optimization of electroporation. The copy number of the plasmid was shown to be very low, as only a little amount of plasmid could be isolated from large culture volume. Even with optimized electroporation method, the repB-ErmR could not be electroporated into Ln. carnosum 4010. This indicates that the larger constructions are nearly impossible to be transferred into the strain Ln. carnosum 4010.
In conclusion, it was confirmed that the plasmid replication gene repB of Ln. carnosum 4010 is functional in Lc. lactis. Due to the low copy number of the plasmid repB-ErmR, the amount of plasmid was definitely a problem in electroporation. Therefore, for studying the efficiency of electroporation, the plasmid amount needs to be increased.…
Subjects/Keywords: Leuconostoc; ABC transporter; bacteriocin; electroporation; Food Science; Food Science; Food Science; Leuconostoc; ABC transporter; bacteriocin; electroporation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cai, Y. (2018). Secretion of bacteriocins in Leuconostoc carnosum 4010. (Masters Thesis). University of Helsinki. Retrieved from http://hdl.handle.net/10138/236075
Chicago Manual of Style (16th Edition):
Cai, Yida. “Secretion of bacteriocins in Leuconostoc carnosum 4010.” 2018. Masters Thesis, University of Helsinki. Accessed April 12, 2021.
http://hdl.handle.net/10138/236075.
MLA Handbook (7th Edition):
Cai, Yida. “Secretion of bacteriocins in Leuconostoc carnosum 4010.” 2018. Web. 12 Apr 2021.
Vancouver:
Cai Y. Secretion of bacteriocins in Leuconostoc carnosum 4010. [Internet] [Masters thesis]. University of Helsinki; 2018. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/10138/236075.
Council of Science Editors:
Cai Y. Secretion of bacteriocins in Leuconostoc carnosum 4010. [Masters Thesis]. University of Helsinki; 2018. Available from: http://hdl.handle.net/10138/236075
14.
Mathieu, Khadija.
Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance.
Degree: Docteur es, Biochimie, 2019, Lyon
URL: http://www.theses.fr/2019LYSE1052
► Au cours des dernières décennies, une augmentation non négligeable du phénomène de résistance aux antibiotiques des bactéries a été observée. Ces bactéries possèdent plusieurs mécanismes…
(more)
▼ Au cours des dernières décennies, une augmentation non négligeable du phénomène de résistance aux antibiotiques des bactéries a été observée. Ces bactéries possèdent plusieurs mécanismes de résistance parmi lesquels l’utilisation de transporteurs de type MDR (MultiDrug Resistance) dont certains appartiennent à la famille des transporteurs ABC (ATP-Binding Cassette). Les transporteurs ABC sont des protéines membranaires et ubiquitaires qui possèdent une topologie commune avec deux domaines transmembranaires et deux domaines cytoplasmiques. Les transporteurs ABC de type exportateur permettent le transport de molécules à l’extérieur de la cellule en utilisant l’énergie fournie par l’hydrolyse de l’ATP. PatA-PatB est un transporteur ABC de Streptococcus pneumoniae, un pathogène humain responsable de pneumonies et de méningites. Cette protéine est impliquée dans la résistance de ce pathogène à des antibiotiques de types fluoroquinolones. Pour étudier son mécanisme moléculaire, nous avons optimisé la surexpression fonctionnelle de ce transporteur chez Escherichia coli. Ainsi, nous avons pu caractériser son activité de transport de drogues et son activité d’hydrolyse de nucléotides. Ces expériences ont révélé que PatA-PatB a la particularité d’utiliser préférentiellement le GTP comme source d’énergie, contrairement aux autres membres de cette famille. Afin d’identifier l’origine de cette propriété au niveau moléculaire, des expériences de mutagénèse dirigée ont été effectuées et nous avons ainsi identifié deux simples mutants qui transportent les drogues aussi bien avec du GTP que de l’ATP
The excessive use of antibiotics during the past decades led to the amplification of multidrug resistance in pathogenic bacteria. Bacteria have developed several mechanisms of antibiotic resistance. One of them involves the antibiotic efflux by MDR (MultiDrug Resistance) transporters, some of which belong to the ABC (ATP-Binding Cassette) transporter family. ABC transporter are ubiquitous membrane proteins with a conserved topology comprising four domains : two «TransMembrane Domain» and two cytoplasmic domains named « Nucleotide-Binding Domain ». ABC exporters expel drugs outside the bacteria using the energy of ATP hydrolysis. PatA-PatB is an ABC transporter from Streptococcus pneumoniae, a human pathogen bacterium responsible for pneumonia and meningitis. This protein is involved in S. pneumoniae resistance against fluoroquinolone antibiotics. To study the molecular mechanism, we optimized the functional expression of this transporter in Escherichia coli. Then, we characterized its drug transport activity and its nucleotide hydrolysis activity. These experiments showed that PatA-PatB, in contrast to other members of the ABC superfamily, preferentially uses GTP as energy supply. To identify the origin of this property at a molecular level, mutagenesis experiments were performed and we identified two mutants capable of an even drug transport with ATP and GTP
Advisors/Committee Members: Jault, Jean-Michel (thesis director), Orelle, Cédric (thesis director).
Subjects/Keywords: Transporteur ABC; MDR; GTP; Streptococcus pneumoniae; Antibiotique; ABC Transporter; MDR; GTP; Streptococcus pneumoniae; Antibiotic; 570
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APA (6th Edition):
Mathieu, K. (2019). Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2019LYSE1052
Chicago Manual of Style (16th Edition):
Mathieu, Khadija. “Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance.” 2019. Doctoral Dissertation, Lyon. Accessed April 12, 2021.
http://www.theses.fr/2019LYSE1052.
MLA Handbook (7th Edition):
Mathieu, Khadija. “Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance.” 2019. Web. 12 Apr 2021.
Vancouver:
Mathieu K. Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance. [Internet] [Doctoral dissertation]. Lyon; 2019. [cited 2021 Apr 12].
Available from: http://www.theses.fr/2019LYSE1052.
Council of Science Editors:
Mathieu K. Caractérisation d’un transporteur ABC d’antibiotiques de Streptococcus pneumoniae, PatA-PatB : Characterization of PatA-PatB, a Streptococcus pneumoniae ABC transporter involved in antibiotic resistance. [Doctoral Dissertation]. Lyon; 2019. Available from: http://www.theses.fr/2019LYSE1052
15.
Vorac, Jaroslav.
Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides.
Degree: Docteur es, Biologie structurale et nanobiologie, 2016, Université Grenoble Alpes (ComUE)
URL: http://www.theses.fr/2016GREAV009
► Streptococcus pneumoniae, le pneumocoque, est un pathogène majeur causant plus d'un million de morts par an dans le monde. De plus en plus de souches…
(more)
▼ Streptococcus pneumoniae, le pneumocoque, est un pathogène majeur causant plus d'un million de morts par an dans le monde. De plus en plus de souches de pneumocoques sont résistants aux antibiotiques, en faisant un problème majeur de santé publique dans le monde. Une partie des ces antibiotiques sont les peptides anti-microbiens (AMP), qui sont produit aussi bien par l'hôte que des bactéries pathogènes en tant que premier système de défense. On trouve dans le pneumocoque un transporteur ABC (ATP-Binding Cassette) lié à un système de deux composants (TCS) – la kinase d'histidine (HK) et le régulateur de réponse (RR), qui cible les AMP. Récemment, il a été démontré, que l'absence du transporteur ABC augmente la sensibilité à la bacitracine. Dans ce projet, nous avons essayé à comprendre le mécanisme fonctionnel entre le transporteur ABC et TCS en utilisant des outils in vivo et in vitro.
Streptococcus pneumoniae, the pneumococcus, is a major human pathogen causing over a million deaths each year. Many pneumococcal strains display resistance towards antibiotics causing world-wide health concern. Some of these antibiotics are antimicrobial peptides (AMP), which are produced as a primary defense by hosts as well as pathogens. The pneumococcus harbors a system comprised of an ATP-binding cassette (ABC) transporter and a two-component system (TCS) composed of a histidine kinase (HK) and a response regulator (RR), which targets these molecules. It has been shown recently that the removal of this ABC transporter increases the sensitivity of the bacteria towards bacitracin. In this project, we tried to understand the functioning mechanism of the ABC transporter and the co-operation with the TCS using both in vivo and in vitro techniques.
Advisors/Committee Members: Jault, Jean-Michel (thesis director), Durmort, Claire (thesis director).
Subjects/Keywords: Transporteurs ABC; Résistance aux drogues; Transporteurs MDR; ABC transporter; Resistance; Peptides; 570
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APA (6th Edition):
Vorac, J. (2016). Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides. (Doctoral Dissertation). Université Grenoble Alpes (ComUE). Retrieved from http://www.theses.fr/2016GREAV009
Chicago Manual of Style (16th Edition):
Vorac, Jaroslav. “Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides.” 2016. Doctoral Dissertation, Université Grenoble Alpes (ComUE). Accessed April 12, 2021.
http://www.theses.fr/2016GREAV009.
MLA Handbook (7th Edition):
Vorac, Jaroslav. “Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides.” 2016. Web. 12 Apr 2021.
Vancouver:
Vorac J. Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides. [Internet] [Doctoral dissertation]. Université Grenoble Alpes (ComUE); 2016. [cited 2021 Apr 12].
Available from: http://www.theses.fr/2016GREAV009.
Council of Science Editors:
Vorac J. Le fonctionnement du transporteur ABC de Streptococcus pneumoniae impliqué dans la résistance contre les peptides antimicrobiens : Fuctioning mechanism of an ABC transporter from Streptococcus pneumoniae involved in the resistance towards antimicrobial peptides. [Doctoral Dissertation]. Université Grenoble Alpes (ComUE); 2016. Available from: http://www.theses.fr/2016GREAV009
Ruhr Universität Bochum
16.
Overlöper, Aaron Falk.
Characterization of small RNAs in Agrobacterium
tumefaciens.
Degree: 2014, Ruhr Universität Bochum
URL: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-41665
► Agrobacterium tumefaciens ist ein weit verbreitetes Pflanzen-pathogenes Bakterium. In den letzten Jahren wurde die generelle Bedeutung von kleinen regulatorischen RNAs (sRNAs) in der Regulation der…
(more)
▼ Agrobacterium tumefaciens ist ein weit verbreitetes
Pflanzen-pathogenes Bakterium. In den letzten Jahren wurde die
generelle Bedeutung von kleinen regulatorischen RNAs (sRNAs) in der
Regulation der Genexpression in Bakterien erkannt. Ein Teil dieser
Arbeit befasste sich damit kleine regulatorische RNAs (sRNAs) in
Agrobacterium zu identifizieren. RNA- Sequenzierungen (dRNA-seq)
lieferten zahlreiche neue sRNAs. Ein zweites Projekt dieser Arbeit
umfasste die funktionelle Charakterisierung von AbcR1, eine sRNA
die eine Vielzahl an mRNAs beeinflusst. Einige dieser mRNAs
kodieren für Proteine, die an der Aufnahme von Aminosäuren und
Zuckern, in der Signaltransduktion der Virulenz-Kaskade und an der
Nährstoffaufnahme nach Infektion von Pflanzen beteiligt sind. Die
vorliegende Arbeit liefert wertvolle neue Informationen zur
umfassenden sRNA- Regulation in der Physiologie von A. tumefaciens
und von verwandten Bakterien, die zu Bakterien-Wirtsinteraktion
befähigt sind.
Advisors/Committee Members: Biologie.
Subjects/Keywords: Small RNA; Agrobacterium; RNS-Bindung; Proteobakterien;
ABC-Transporter
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Overlöper, A. F. (2014). Characterization of small RNAs in Agrobacterium
tumefaciens. (Thesis). Ruhr Universität Bochum. Retrieved from http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-41665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Overlöper, Aaron Falk. “Characterization of small RNAs in Agrobacterium
tumefaciens.” 2014. Thesis, Ruhr Universität Bochum. Accessed April 12, 2021.
http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-41665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Overlöper, Aaron Falk. “Characterization of small RNAs in Agrobacterium
tumefaciens.” 2014. Web. 12 Apr 2021.
Vancouver:
Overlöper AF. Characterization of small RNAs in Agrobacterium
tumefaciens. [Internet] [Thesis]. Ruhr Universität Bochum; 2014. [cited 2021 Apr 12].
Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-41665.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Overlöper AF. Characterization of small RNAs in Agrobacterium
tumefaciens. [Thesis]. Ruhr Universität Bochum; 2014. Available from: http://nbn-resolving.de/urn/resolver.pl?urn=urn:nbn:de:hbz:294-41665
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
17.
松本, 博文.
ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割.
Degree: 博士(医学), 2014, Nagasaki University / 長崎大学
URL: http://hdl.handle.net/10069/35903
► ATP-binding cassette (ABC) transporters are involved in chemotherapy resistance. Multidrug-resistance protein 8 (ABCC11/MRP8) is also involved in 5-fluorouracil (5-FU) metabolism. 5-FU and its derivatives are…
(more)
▼ ATP-binding cassette (ABC) transporters are involved in chemotherapy resistance. Multidrug-resistance protein 8 (ABCC11/MRP8) is also involved in 5-fluorouracil (5-FU) metabolism. 5-FU and its derivatives are widely used in the treatment of gastrointestinal tract cancers, but little is known about the contribution of ABCC11/MRP8 to gastrointestinal tract and related cancers. Here, we report our investigation of ABCC11/MRP8 expression in normal and cancerous gastrointestinal tract tissues and reveal its novel role in the gastric mucosa. In tissue microarray and surgically resected cancer specimens, immunohistochemical (IHC) staining revealed significantly reduced expression of ABCC11/ MRP8 in gastrointestinal tract cancers compared with other cancers. In contrast, strong ABCC11/MRP8 expression was observed in normal gastric mucosa. Additional immuno-fluorescence assays revealed co-localization of ABCC11/MRP8 and pepsinogen I in normal gastric chief cells. Quantitative PCR and Western blot analysis also revealed significant expression of ABCC11/MRP8 in fundic mucosa where the chief cells are mainly located. Furthermore, the ABCC11 mRNA-suppressed NCI-N87 gastric cancer cell line failed to secret pepsinogen I extracellularly. Thus, low expression of ABCC11/MRP8 is consistent with chemotherapeutic regimens using 5-FU and its derivatives in gastrointestinal tract cancers. Our results indicated a novel function of ABCC11/MRP8 in the regulation of pepsinogen I secretion in the normal gastric chief cells.
Subjects/Keywords: ABC transporter; ABCC11/MRP8; Gastric chief cells; Gastrointestinal tract; Pepsinogen I
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APA (6th Edition):
松本, . (2014). ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割. (Thesis). Nagasaki University / 長崎大学. Retrieved from http://hdl.handle.net/10069/35903
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
松本, 博文. “ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割.” 2014. Thesis, Nagasaki University / 長崎大学. Accessed April 12, 2021.
http://hdl.handle.net/10069/35903.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
松本, 博文. “ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割.” 2014. Web. 12 Apr 2021.
Vancouver:
松本 . ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割. [Internet] [Thesis]. Nagasaki University / 長崎大学; 2014. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/10069/35903.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
松本 . ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for Pepsinogen Secretion : ABCC11/MRP8の消化管における発現とペプシノーゲン産生における新規的役割. [Thesis]. Nagasaki University / 長崎大学; 2014. Available from: http://hdl.handle.net/10069/35903
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
18.
Rimington, Tracy.
Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae.
Degree: 2014, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:231349
► Mutations in the eukaryotic integral membrane protein Cystic Fibrosis Transmembrane conductance Regulator (CFTR) cause the hereditary disease cystic fibrosis (CF). CFTR functions as an ion…
(more)
▼ Mutations in the eukaryotic integral membrane
protein Cystic Fibrosis Transmembrane conductance Regulator (CFTR)
cause the hereditary disease cystic fibrosis (CF). CFTR functions
as an ion channel at the surface of epithelial cells and regulates
the movement of chloride ions and water across the plasma membrane.
CFTR is difficult to express and purify in heterologous systems due
to its propensity to form insoluble aggregates and its
susceptibility to degradation. Obtaining good yields of highly
purified CFTR has proven problematic and contributes to our limited
understanding of the structure and function of the protein. The
most prevalent disease causing mutation, F508del, results in
misfolded CFTR which is particularly unstable and is quickly
targeted for degradation by the host system and is prevented from
being trafficked to the plasma membrane. There are limited
treatment options for patients with the F508del mutation and it is
therefore of significant interest within CF research. New methods
and assays are required to identify potential compounds which could
correct the F508del mutation. This thesis investigates the use of
Saccharomyces cerevisiae to express and purify codon optimised
recombinant CFTR. The use of a green fluorescent protein (GFP) tag
enabled quick and simple detection of CFTR in whole cells and after
extraction from the plasma membrane. By optimising the culture
conditions for CFTR expression and detergent solubilisation
conditions, relatively high yields of full-length protein were
obtained. When used as a chemical chaperone at the time of inducing
CFTR expression, glycerol increased yields of full-length protein.
Degradation of CFTR could be limited by inducing expression at an
optimal cell density and by harvesting cells within a specific time
window. CFTR was extracted by solubilisation in the mild detergent
dodecyl-β-D-maltopyranoside (DDM) in the presence of up to 1 M NaCl
with up to ~87% efficiency in some cases. Using a gene optimisation
strategy in which additional purification tags and a yeast
Kozak-like sequence were added, the human CFTR (hCFTR) protein was
expressed and purified. Fluorescence microscopy revealed CFTR
localisation at the periphery of yeast cells. Immunoaffinity
chromatography facilitated by the GFP tag at the C terminus of CFTR
produced protein of up to 95% purity. An assessment of the thermal
stability of this highly purified CFTR using a fluorescent probe
binding assay revealed a denaturation midpoint (Tm) of ~43 degC.
The ability of this assay to determine the stability of CFTR is
encouraging and there is the potential to further develop it in a
high-throughput manner to identify compounds which stabilise the
F508del protein and which may hold the key to developing new
treatments for CF.
Subjects/Keywords: CFTR; ABCC7; cystic fibrosis; membrane protein; GFP;
ion channel; ABC-transporter
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APA ·
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APA (6th Edition):
Rimington, T. (2014). Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:231349
Chicago Manual of Style (16th Edition):
Rimington, Tracy. “Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae.” 2014. Doctoral Dissertation, University of Manchester. Accessed April 12, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:231349.
MLA Handbook (7th Edition):
Rimington, Tracy. “Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae.” 2014. Web. 12 Apr 2021.
Vancouver:
Rimington T. Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2021 Apr 12].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:231349.
Council of Science Editors:
Rimington T. Expression, Purification and Characterisation of the
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in
Saccharomyces cerevisiae. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:231349
University of Toronto
19.
Manan, Yaseen.
Investigating the Structure of MacB, an ABC Transporter Protein.
Degree: 2015, University of Toronto
URL: http://hdl.handle.net/1807/70462
► Despite the need to understand membrane proteins at the molecular level, fewer than 2% of the structures in the PDB are of membrane proteins. Detergents…
(more)
▼ Despite the need to understand membrane proteins at the molecular level, fewer
than 2% of the structures in the PDB are of membrane proteins. Detergents have been
the most powerful tool used in structural studies but have limitations. As a result, novel
membrane mimetics have been an area of intense investigation. This thesis looks at the
crystallization pipeline of an ABC transporter, L. lactis MacB. A 10-His-tagged L. lactis
MacB clone was purified using Ni-NTA purification and size exclusion chromatography
in n-decyl-β-D-Maltoside. The protein was characterized using a ultracentrifugation
assay, size exclusion chromatography and ATPase activity assay to find optimum
crystal screening conditions. Detergent screening also identified 6 other classical
detergents for crystal screening. Lastly, the protein was exchanged into 10 different
LPDs, DMPC/CHAPSO bicelles and monoolein based cubic phase. While no crystals
were obtained, this thesis seeks to highlight some of the
challenges of crystallizing a novel membrane protein.
M.Sc.
Advisors/Committee Members: Privé, Gil, Biochemistry.
Subjects/Keywords: ABC Transporter; Drug; Exporter; MacB; Membrane Proteins; X-Ray Crystallography; 0487
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APA (6th Edition):
Manan, Y. (2015). Investigating the Structure of MacB, an ABC Transporter Protein. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/70462
Chicago Manual of Style (16th Edition):
Manan, Yaseen. “Investigating the Structure of MacB, an ABC Transporter Protein.” 2015. Masters Thesis, University of Toronto. Accessed April 12, 2021.
http://hdl.handle.net/1807/70462.
MLA Handbook (7th Edition):
Manan, Yaseen. “Investigating the Structure of MacB, an ABC Transporter Protein.” 2015. Web. 12 Apr 2021.
Vancouver:
Manan Y. Investigating the Structure of MacB, an ABC Transporter Protein. [Internet] [Masters thesis]. University of Toronto; 2015. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/1807/70462.
Council of Science Editors:
Manan Y. Investigating the Structure of MacB, an ABC Transporter Protein. [Masters Thesis]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/70462
Virginia Commonwealth University
20.
Atia, Sawsan.
SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS.
Degree: MS, Microbiology & Immunology, 2013, Virginia Commonwealth University
URL: https://doi.org/10.25772/7H6Z-DX09
;
https://scholarscompass.vcu.edu/etd/3054
► The bacterium Streptococcus sanguinis is a primary member of the human oral microflora and also has been recognized as a key player in the bacterial…
(more)
▼ The bacterium Streptococcus sanguinis is a primary member of the human oral microflora and also has been recognized as a key player in the bacterial colonization of the mouth. It is considered the most common viridians streptococcal species implicated in infective endocarditis. In all kingdoms of life, ATP binding cassette (
ABC) transporters are essential to many cellular functions. Sequencing of the SK36 genome provided the opportunity to study
ABC transporter mutants and their relationship with acidity of the oral environment. Despite numerous studies that have focused on carbohydrate uptake systems in closely related streptococcal species such as S. mutans, S. pneumonia and S. pyogenes, the mechanism of the response of these
ABC transporters to acidic conditions in S. sanguinis is still unknown. The capability of S. sanguinis to adapt in these harsh environments suggests this bacterium is capable of responding to various environmental stimuli. The purpose of this study was to examine
ABC mutants to identify functions that contribute to acid tolerance in S. sanguinis.
This study demonstrates that two acid-sensitive mutant genes, SSA_1507 and SSA_1508, identify genes involved in acid tolerance. The two mutants grew on different sugars and none of them showed a defect in sugar utilization at acid pH. We couldn’t recognize any significant differences in sugar uptake for the two acid sensitive mutants or in mutants of their neighboring genes. Thus, the observed acid sensitivity is not due to a failure to take up any of the common sugars tested. The cytoplasmic pH of S. sanguinis was studied with the fluorescent pH indicator (BCECF) and SK36 was observed to have a wider pH range than either of the two acid-sensitive mutants SSA_1507 or SSA_1508. In these two mutants, intracellular pH was not as well maintained. At all pH values tested, the mutants displayed a lower intracellular pH than the wild type. These observations indicate that the cell membrane of these two mutants is unable to protect the interior components from adverse effects of higher pH values and lower pH values, and prove that these two mutant genes SSA_1507 and SSA_1508 are unable to grow in lower pH values. These results support a role for these
ABC transporters in proton pump or export and indicate that the mutants are less able to pump out protons.
Advisors/Committee Members: Ping Xu, Gail Christie, Imad Damaj.
Subjects/Keywords: ABC transporter; Acid stress response; Streptococcus sanguinis; Medicine and Health Sciences
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APA (6th Edition):
Atia, S. (2013). SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS. (Thesis). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/7H6Z-DX09 ; https://scholarscompass.vcu.edu/etd/3054
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Atia, Sawsan. “SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS.” 2013. Thesis, Virginia Commonwealth University. Accessed April 12, 2021.
https://doi.org/10.25772/7H6Z-DX09 ; https://scholarscompass.vcu.edu/etd/3054.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Atia, Sawsan. “SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS.” 2013. Web. 12 Apr 2021.
Vancouver:
Atia S. SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS. [Internet] [Thesis]. Virginia Commonwealth University; 2013. [cited 2021 Apr 12].
Available from: https://doi.org/10.25772/7H6Z-DX09 ; https://scholarscompass.vcu.edu/etd/3054.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Atia S. SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN
STREPTOCOCCUS SANGUINIS. [Thesis]. Virginia Commonwealth University; 2013. Available from: https://doi.org/10.25772/7H6Z-DX09 ; https://scholarscompass.vcu.edu/etd/3054
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Guelph
21.
Vitsupakorn, Danoo.
Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter.
Degree: MS, Department of Molecular and Cellular Biology, 2014, University of Guelph
URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8398
► The ABC multidrug transporter P-glycoprotein (Pgp, ABCB1) can transport structurally diverse substrates from the lipid bilayer. Pgp binds its substrates inside a large pocket with…
(more)
▼ The
ABC multidrug
transporter P-glycoprotein (Pgp, ABCB1) can transport structurally diverse substrates from the lipid bilayer. Pgp binds its substrates inside a large pocket with multiple sub-sites. In the present work, a thiol-reactive agent, (2-pyridyl)dithiobimane, was covalently linked to 5 of the 7 Cys residues in hamster Pgp, with substantial ATPase activity retained. Three of the labelled Cys residues are located in the transmembrane domain, close to the substrate-binding pocket. Binding affinity determination using Trp and bimane fluorescence for tetramethylrosamine (R-site), Hoechst 33342 (H-site) and 6-(dimethylamino)-2-[4-[4-(dimethylamino)phenyl]-1,3-butadienyl]-1-ethyl perchlorate (both sites), showed similar Kd values for native Pgp and Pgp-bimane adducts, suggesting that the binding pocket can accommodate more than one substrate simultaneously. Reconstituted Pgp-bimane proteoliposomes showed the ability to transport all three substrates across the membrane, although with lower Vmax values compared to native Pgp. Thus, the Pgp-bimane adduct can transport substrates when more than one substrate occupies the binding pocket.
Advisors/Committee Members: Sharom, Frances (advisor).
Subjects/Keywords: membrane protein; ABC transporter; P-glycoprotein; drug binding; drug transport
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APA (6th Edition):
Vitsupakorn, D. (2014). Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8398
Chicago Manual of Style (16th Edition):
Vitsupakorn, Danoo. “Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter.” 2014. Masters Thesis, University of Guelph. Accessed April 12, 2021.
https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8398.
MLA Handbook (7th Edition):
Vitsupakorn, Danoo. “Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter.” 2014. Web. 12 Apr 2021.
Vancouver:
Vitsupakorn D. Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter. [Internet] [Masters thesis]. University of Guelph; 2014. [cited 2021 Apr 12].
Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8398.
Council of Science Editors:
Vitsupakorn D. Drug-drug interactions in the binding pocket of P-glycoprotein multidrug resistant transporter. [Masters Thesis]. University of Guelph; 2014. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/8398
22.
Rahman, Hadiar.
Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance.
Degree: 2020, The Catholic University of America
URL: http://hdl.handle.net/1961/cuislandora:213974
► Multidrug resistance to antifungals and chemotherapeutic drugs is a huge clinical problem for treatment of fungal infections and cancers. Overexpression or alteration of multidrug efflux…
(more)
▼ Multidrug resistance to antifungals and chemotherapeutic drugs is a huge clinical problem for treatment of fungal infections and cancers. Overexpression or alteration of multidrug efflux ATP Binding Cassette (ABC) transporters is often associated with this broad-spectrum of resistance. Pleiotropic Drug Response 5 gene (PDR5) in Saccharomyces cerevisiae defines a subclass of important fungal efflux pumps. The characterization of mutations in this transporter uncovered two novel mechanism of increased resistance. The first mutation, A666G, resulted in enhanced resistance without increasing either the amount of protein in the plasma membrane or the ATPase activity. In fluorescence-quenching transport assays with rhodamine 6G in purified plasma membrane vesicles, the initial rates of rhodamine 6G fluorescence quenching of both the wild-type and mutant showed a strong dependence on ATP concentration, but were about twice as high in the latter. Plots of initial rate of fluorescence quenching versus ATP concentration exhibited strong cooperativity that was significantly increased in the A666G mutant and accounted for the observed enhancement in resistance. Alanine substitution mutations in six serine residues of linker-2 all exhibited increased resistance to xenobiotic agents. Biochemical studies of these nonsynonymous mutants demonstrated that they have increased steady-state levels of Pdr5 protein expression and thus enhanced resistance. Quantitative-RT PCR and metabolic labelling experiments demonstrated that the mutants had levels of PDR5 mRNA that were two to three times as high as in the isogenic wild-type strain because the transcript half-life was increased. These data demonstrate that the nucleotides encoding unconserved amino acids may be used to regulate expression and suggest that Pdr5 has a newly discovered RNA stability element within its coding region.
Biology
Genetics
Biochemistry
ABC Transporter, Cooperativity, Linker-2, mRNA, Nonsynonymous mutation, Pdr5
Biology
Degree Awarded: Ph.D. Biology. The Catholic University of America
Advisors/Committee Members: The Catholic University of America (Degree granting institution), Golin, John (Thesis advisor), Tuma, Pamela (Committee member), Choy, John (Committee member).
Subjects/Keywords: ABC Transporter; Cooperativity; Linker-2; mRNA; Nonsynonymous mutation; Pdr5
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APA (6th Edition):
Rahman, H. (2020). Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance. (Thesis). The Catholic University of America. Retrieved from http://hdl.handle.net/1961/cuislandora:213974
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Rahman, Hadiar. “Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance.” 2020. Thesis, The Catholic University of America. Accessed April 12, 2021.
http://hdl.handle.net/1961/cuislandora:213974.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Rahman, Hadiar. “Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance.” 2020. Web. 12 Apr 2021.
Vancouver:
Rahman H. Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance. [Internet] [Thesis]. The Catholic University of America; 2020. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/1961/cuislandora:213974.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Rahman H. Serine Residues in Linker-2 of the Yeast Multidrug Transporter Pdr5 Modulate Drug Resistance. [Thesis]. The Catholic University of America; 2020. Available from: http://hdl.handle.net/1961/cuislandora:213974
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
23.
Thonghin, Nopnithi.
Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1).
Degree: 2018, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317540
► P-glycoprotein (P-gp or ABCB1) is a membrane-bound active transporter belonging to the ABC protein superfamily. It is responsible for xenobioIc efflux and also contributes to…
(more)
▼ P-glycoprotein (P-gp or ABCB1) is a membrane-bound
active
transporter belonging to the
ABC protein superfamily. It is
responsible for xenobioIc efflux and also contributes to multidrug
resistance in diverse diseases including cancer and epilepsy. P-gp
has been increasingly recognised as a potential target for future
therapeutics. Although the protein has been studied for decades,
understanding of the P-gp transport mechanism is still incomplete.
Two P-gp orthologues, mouse (m) and human (h), were therefore
expressed in yeasts and purified in the presence of the detergent,
n-Dodecyl-β-D- Maltoside (DDM). Purified proteins were examined
for aggregation and monodispersity via dynamic light scattering
(DLS) and their thermal stability was determined by an assay using
a thiol-specific dye (CPM). ATPase activity, measured in a
detergent environment, showed that the proteins were active with a
basal activity of 60 ± 4 and 35 ± 3 nmol/min/mg for mP-gp and
hP-gp, respectively. Crystallisation trials were conducted in the
presence of nucleotide. In meso crystallisation using commercial
monoolein pre- dispensed plates yielded hexagonal crystal-like
objects however they failed to diffract X- rays. P-gp samples were
also subjected to cryo-EM where mP-gp in the post-hydrolytic
(ADP-bound, vanadate-trapped) state provided the highest resolution
dataset that led to a reconstruction of 3D density map at the
resolution of 7.9 Ã… which showed an inward- facing conformation.
Rigid-body model fitting unveiled densities that were not accounted
for by the fitted model illustrating new features such as bound
ADP, extended NBD1- TMD2 linker and alternative allocrite-binding
sites. Ultimately, the knowledge of P-gp conformation alteration
was enhanced and a refined alternating access mechanism of P- gp
was proposed based upon information derived from this
study.
Advisors/Committee Members: DOIG, ANDREW AJ, Ford, Robert, Doig, Andrew.
Subjects/Keywords: cryo-EM; P-gp; ABC transporter; membrane protein; protein structure
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Thonghin, N. (2018). Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1). (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317540
Chicago Manual of Style (16th Edition):
Thonghin, Nopnithi. “Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1).” 2018. Doctoral Dissertation, University of Manchester. Accessed April 12, 2021.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317540.
MLA Handbook (7th Edition):
Thonghin, Nopnithi. “Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1).” 2018. Web. 12 Apr 2021.
Vancouver:
Thonghin N. Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1). [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Apr 12].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317540.
Council of Science Editors:
Thonghin N. Structural studies of the multi-drug resistance protein
P-glycoprotein (ABCB1). [Doctoral Dissertation]. University of Manchester; 2018. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:317540
Brigham Young University
24.
Vuppada, Ramesh Krishna.
Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter.
Degree: MS, 2017, Brigham Young University
URL: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7641&context=etd
► Phosphate is an essential compound for life. Escherichia coli employs a signal transduction pathway that controls the expression of genes that are required for the…
(more)
▼ Phosphate is an essential compound for life. Escherichia coli employs a signal transduction pathway that controls the expression of genes that are required for the high-affinity acquisition of phosphate and the utilization of alternate sources of phosphorous. These genes are only expressed when environmental phosphate is limiting. The seven genes for this signaling pathway encode the two-component regulatory proteins PhoB and PhoR, as well as the high-affinity phosphate transporter PstSCAB and an auxiliary protein called PhoU. As the sensor kinase PhoR has no periplasmic sensory domain, the mechanism by which these cells sense environmental phosphate is not known. This paper explores the hypothesis that it is the alternating conformations of the PstSCAB transporter which are formed as part of the normal phosphate transport cycle that signal phosphate sufficiency or phosphate limitation. We tested two variants of PstB that are predicted to lock the protein in either of two conformations for their signaling output. We observed that the pstBQ160K mutant, predicted to reside in an inward facing, open conformation signaled phosphate sufficiency whereas the pstBE179Q mutant, predicted to reside in an outward facing, closed conformation signaled phosphate starvation. Neither mutant showed phosphate transport.
Subjects/Keywords: phosphate homeostasis; two-component signal transduction; histidine kinase; ABC transporter; Microbiology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Vuppada, R. K. (2017). Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter. (Masters Thesis). Brigham Young University. Retrieved from https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7641&context=etd
Chicago Manual of Style (16th Edition):
Vuppada, Ramesh Krishna. “Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter.” 2017. Masters Thesis, Brigham Young University. Accessed April 12, 2021.
https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7641&context=etd.
MLA Handbook (7th Edition):
Vuppada, Ramesh Krishna. “Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter.” 2017. Web. 12 Apr 2021.
Vancouver:
Vuppada RK. Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter. [Internet] [Masters thesis]. Brigham Young University; 2017. [cited 2021 Apr 12].
Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7641&context=etd.
Council of Science Editors:
Vuppada RK. Phosphate Signaling Through Alternate Conformations of the PstSCAB Phosphate Transporter. [Masters Thesis]. Brigham Young University; 2017. Available from: https://scholarsarchive.byu.edu/cgi/viewcontent.cgi?article=7641&context=etd
Boston University
25.
Santoso, Clarissa Stephanie.
Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary.
Degree: 2017, Boston University
URL: http://hdl.handle.net/2144/31673
► Programmed cell death (PCD) is an essential biological process in animal development and tissue homeostasis that is necessary to ensure the physiological well-being of the…
(more)
▼ Programmed cell death (PCD) is an essential biological process in animal development and tissue homeostasis that is necessary to ensure the physiological well-being of the organism. During PCD, phagocytes facilitate the selective removal of excess, damaged, and potentially deleterious cells, in a multi-step engulfment process. Genetic studies in Drosophila melanogaster, Caenorhabditis elegans, and mammals have identified two evolutionarily conserved signal transduction pathways that act redundantly to regulate engulfment: the CED-1/-6/-7 and CED-2/-5/-12 pathways. Of these cell death (CED) proteins, the
ABC transporter CED-7 is the only protein reported to be required in both the engulfing cell and the dying cell. However, its function in the cell death process remains the most enigmatic and the ced-7 ortholog previously has not been identified in Drosophila. Homology searches revealed a family of putative ced-7 orthologs that encode transporters of the ABCA family in Drosophila. To determine which of these genes functions similarly to ced-7/ABCA1 in PCD, we analyzed their engulfment function in oogenesis, during which 15 germ cells in each egg chamber undergo programmed cell death and are removed by neighboring phagocytic follicle cells. It has been shown that genetically knocking down individual engulfment genes results in inefficient clearance of the germ cells, which then persist in late-stage egg chambers. Only two of the putative ced-7/ABCA1 genes are expressed significantly in the ovary, CG31731 and CG1718, and we have characterized these genes using transposon insertions, deficiencies, and RNAi knockdowns. Our genetic analysis reveals that CG31731 is necessary for germ cell clearance in the Drosophila ovary. Immunostaining shows that genetically knocking down CG31731 results in uncleared germ cells which persist in late-stage egg chambers. Altogether, our findings suggest that CED-7/ABCA1/CG31731 play evolutionarily conserved roles during engulfment.
Advisors/Committee Members: McCall, Kim (advisor).
Subjects/Keywords: Molecular biology; ABC transporter; Drosophila; Engulfment; Genetics; Programmed cell death
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APA ·
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Export
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APA (6th Edition):
Santoso, C. S. (2017). Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary. (Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/31673
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Santoso, Clarissa Stephanie. “Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary.” 2017. Thesis, Boston University. Accessed April 12, 2021.
http://hdl.handle.net/2144/31673.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Santoso, Clarissa Stephanie. “Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary.” 2017. Web. 12 Apr 2021.
Vancouver:
Santoso CS. Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary. [Internet] [Thesis]. Boston University; 2017. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/2144/31673.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Santoso CS. Analysis of the ABC transporter CG31731 in engulfment during programmed cell death in the Drosophila melanogaster ovary. [Thesis]. Boston University; 2017. Available from: http://hdl.handle.net/2144/31673
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Illinois – Urbana-Champaign
26.
Sasser, Terry.
The regulation of yeast homotypic membrane fusion by class C ABC transporters.
Degree: PhD, 0318, 2013, University of Illinois – Urbana-Champaign
URL: http://hdl.handle.net/2142/44801
► Maintenance of eukaryotic cellular homeostasis requires the fusion of vesicle membranes that is accomplished by a SNARE-mediated mechanism. Membrane fusion is the merger of two…
(more)
▼ Maintenance of eukaryotic cellular homeostasis requires the fusion of vesicle membranes that is accomplished by a SNARE-mediated mechanism. Membrane fusion is the merger of two lipid bilayers into one continuous membrane. Multiprotein complexes that have been conserved in eukaryotes carry out the basic reactions of fusion. In Saccharomyces cerevisiae, homotypic vacuole fusion occurs in experimentally defined phases. Fusion priming does not involve contact between vacuoles but includes the disassembly of complexes of SNAREs on the same membrane (cis) by Sec18p (NSF) and its cochaperone Sec17p (a-SNAP). Tethering requires Ypt7p (a Rab GTPase) and the HOPS effecter complex. SNARE complexes, including one R SNARE from a donor vacuole and three Q SNAREs from the acceptor vacuole, are formed in trans during docking of vacuoles. The membranes of the docked vacuoles are drawn together to form the “boundary domain” that resembles flat discs. The outer membranes are not in contact and come together at the boundary membrane to form the vertex ring. The vertex microdomain, enriched in fusogenic lipids and proteins, is the origin of fusion where the outer membranes are joined. Fusion culminates with the internalization of the luminal vesicle and mixing of luminal contents.
The core fusion machinery has been elucidated in liposomes but many regulatory factors are being discovered in the context of the yeast vacuole. Regulatory proteins and lipids as well as lipid modifiers have been described suggesting a complex system that regulates cellular traffic. The
ABC transporter superfamily is present in all organisms and is responsible for actively transporting a wide range of substrates across the lipid bilayer. Several class C
ABC transporters interact with factors that are important in the fusion mechanism while others have been implicated in lipid translocation activity. The yeast vacuole contains five
ABC transporters of the ABCC1 subfamily: Ycf1p, Bpt1p, Ybt1p, Vmr1 and Nft1. This project sought to identify the role of
ABC transporters in membrane fusion as regulators of fusogenic proteins and lipids and their role in the mechanism of remodeling the membrane bilayer as lipid translocators.
Although Ybt1p was originally identified as a bile acid
transporter, it has also been found to function in other capacities including the translocation of phosphatidylcholine to the vacuole lumen and the regulation of Ca2+ homeostasis. We found that deletion of YBT1 enhanced in vitro homotypic vacuole fusion by up to 50% relative to wild type vacuoles. The increased vacuole fusion was not due to aberrant protein sorting of SNAREs or recruitment of factors from the cytosol such as Ypt7p and the HOPS tethering complex. In addition, ybt1Δ vacuoles displayed no observable differences in the formation of SNARE complexes, interactions between SNAREs and HOPS, or formation of vertex microdomains. However, the absence of Ybt1p caused significant changes in Ca2+ transport during fusion. One difference was the prolonged Ca2+ influx exhibited by…
Advisors/Committee Members: Fratti, Rutilio A. (advisor), Fratti, Rutilio A. (Committee Chair), Gennis, Robert B. (committee member), Morrissey, James H. (committee member), Tajkhorshid, Emad (committee member).
Subjects/Keywords: Membrane fusion; Trafficking; ATP-Binding Cassette (ABC) transporter
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sasser, T. (2013). The regulation of yeast homotypic membrane fusion by class C ABC transporters. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/44801
Chicago Manual of Style (16th Edition):
Sasser, Terry. “The regulation of yeast homotypic membrane fusion by class C ABC transporters.” 2013. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 12, 2021.
http://hdl.handle.net/2142/44801.
MLA Handbook (7th Edition):
Sasser, Terry. “The regulation of yeast homotypic membrane fusion by class C ABC transporters.” 2013. Web. 12 Apr 2021.
Vancouver:
Sasser T. The regulation of yeast homotypic membrane fusion by class C ABC transporters. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2013. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/2142/44801.
Council of Science Editors:
Sasser T. The regulation of yeast homotypic membrane fusion by class C ABC transporters. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2013. Available from: http://hdl.handle.net/2142/44801
27.
Denecke, Shane.
Probing insecticide biology using Drosophila melanogaster.
Degree: 2017, University of Melbourne
URL: http://hdl.handle.net/11343/191214
► Insecticides are often used to control insect pests, but resistance to these chemicals arises quickly, leading to agricultural losses and public health concerns. Understanding how…
(more)
▼ Insecticides are often used to control insect pests, but resistance to these chemicals arises quickly, leading to agricultural losses and public health concerns. Understanding how insects cope with insecticides is necessary when designing rational pest management strategies, but much still remains unknown regarding the fate of insecticides once inside the body. Furthermore, the genetic variation that governs an insects ability to survive insecticide exposures has not been fully described.
Here, a 3 pronged approach is applied to study insecticide biology using the model insect Drosophila melanogaster. First, an acute, sub-lethal insecticide response assay was developed, which provided information complementary to that obtained from more common toxicology assays. In particular, behavioural response observed in a hyper-resistant target site mutant suggests additional target sites for the insecticide spinosad. This bioassay was then applied in a forward genetics approach to describe the genetic basis of resistance to the insecticide imidacloprid. This approach identified a variety of neuronal genes and the previously identified drug metabolizing enzyme Cyp6g1, which was explored through genetic manipulation. Finally, a reverse genetics approach was employed in order to study the effect of an ABC transporter protein Mdr65 on insecticide resistance. Removing the gene made the insects more susceptible to a subset of the insecticides tested, and this was confirmed with genetic and chemical complementation tests.
These data provide information both on the genetics and kinetics of insecticide biology. Such information will help to better understand insecticide resistance and design rational resistance management strategies.
Subjects/Keywords: genetics; Drosophila; insecticide; drug resistance; P450; ABC transporter
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Denecke, S. (2017). Probing insecticide biology using Drosophila melanogaster. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/191214
Chicago Manual of Style (16th Edition):
Denecke, Shane. “Probing insecticide biology using Drosophila melanogaster.” 2017. Doctoral Dissertation, University of Melbourne. Accessed April 12, 2021.
http://hdl.handle.net/11343/191214.
MLA Handbook (7th Edition):
Denecke, Shane. “Probing insecticide biology using Drosophila melanogaster.” 2017. Web. 12 Apr 2021.
Vancouver:
Denecke S. Probing insecticide biology using Drosophila melanogaster. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/11343/191214.
Council of Science Editors:
Denecke S. Probing insecticide biology using Drosophila melanogaster. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/191214
Brock University
28.
Woolfson, Kathlyn.
Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
.
Degree: Department of Biological Sciences, 2014, Brock University
URL: http://hdl.handle.net/10464/5686
► The various steps of monoterpene indole alkaloid (MIA) biosynthesis are known to occur in specialized cell types and subcellular compartments. Numerous MIAs display powerful biological…
(more)
▼ The various steps of monoterpene indole alkaloid (MIA) biosynthesis are known to occur in specialized cell types and subcellular compartments. Numerous MIAs display powerful biological activities that have led to their use as pharmaceutical treatments for cancer, hypertension and malaria. Many of these compounds accumulate on the leaf surface of medicinally important Apocynaceae plants, which led to the recent discovery and characterization of an ABC transporter (CrTPT2) that was shown to mobilize catharanthine from its site of biosynthesis in epidermal cells to the leaf surface of Catharanthus roseus. Bioinformatic analysis of transcriptomes from several geographically distant MIA-producing species led to the identification of proteins with high amino acid sequence identity to CrTPT2. Molecular cloning of a similar transporter (VmTPT2) from Vinca minor was carried out and expressed in a yeast heterologous system for transport experiments and functional characterization. In planta studies involved transcript expression analysis of the early MIA biosynthetic gene VmTDC and putative transporter VmTPT2, and alkaloid profile analyses. RT-qPCR results showed that VmTPT2 expression increased 15-fold between the first two leaf pairs, and high levels were maintained across older leaves. The alkaloid accumulation profile on leaf surfaces matched that of VmTPT2 expression, especially for the MIAs vincadifformine and vincamine. Gene expression and alkaloid profile analyses suggest that the functional protein may act as a similar transporter to CrTPT2. However, although VmTPT2 had 88.4% identity at the amino acid level to CrTPT2, it displayed an altered expression pattern in planta across developing leaves, and functional characterization using a previously developed yeast heterologous system was unsuccessful due to difficulties with reproducibility of transport assays.
Subjects/Keywords: ABC transporter;
plant secondary metabolism;
monoterpene indole alkaloids;
Vinca minor;
Apocynaceae
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APA (6th Edition):
Woolfson, K. (2014). Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
. (Thesis). Brock University. Retrieved from http://hdl.handle.net/10464/5686
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Woolfson, Kathlyn. “Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
.” 2014. Thesis, Brock University. Accessed April 12, 2021.
http://hdl.handle.net/10464/5686.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Woolfson, Kathlyn. “Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
.” 2014. Web. 12 Apr 2021.
Vancouver:
Woolfson K. Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
. [Internet] [Thesis]. Brock University; 2014. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/10464/5686.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Woolfson K. Preliminary characterization of VmTPT2, a putative monoterpene indole alkaloid (MIA) transporter from Vinca minor L. (Apocynaceae)
. [Thesis]. Brock University; 2014. Available from: http://hdl.handle.net/10464/5686
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Kansas State University
29.
Kumari, Meera.
The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron.
Degree: PhD, Biochemistry and Molecular
Biophysics Interdepartmental Program, 2015, Kansas State University
URL: http://hdl.handle.net/2097/35784
► In this study, I have used dsRNA-mediated down-regulation of transcripts/proteins of several potential targets in the model beetle, Tribolium castaneum to identify a molecular target…
(more)
▼ In this study, I have used dsRNA-mediated
down-regulation of transcripts/proteins of several potential
targets in the model beetle, Tribolium castaneum to identify a
molecular target of the “chitin inhibitor”, diflubenzuron (DFB).
The elytron of the red flour beetle, T. castaneum, was chosen as
the model tissue for studying the mode of action of DFB and its
molecular target(s). We have standardized the protocol for topical
administration of DFB on precisely aged prepupae to achieve the
desired level of mortality (90-95%) on day 5 of the pharate adult
stage. Exposure of prepupae to DFB at 1000 ppm results in a near
complete loss of chitin in the newly forming adult procuticle of
the elytron and the body wall. Global analysis of transcripts by
RNA Seq was carried out to look for differential expression of
several critical genes of cuticle assembly in these insects
compared to mock-treated controls. Interestingly, genes directly
involved in the biosynthetic pathway of chitin were not among those
affected by DFB. However, immunolocalization studies have shown
that several proteins of chitin metabolism including chitin
synthase A, which is involved in the synthesis of cuticular chitin,
are present in near normal amounts but are mislocalized in
DFB-treated insects. Assays for chitin synthase using elytral
extracts have indicated that the enzyme preparations from
DFB-treated insects are catalytically inactive. By using RNA
interference and competition studies with fluorescently-tagged
glibenclamide (a sulfonylurea compound) or DFB, we have identified
a long-sought molecular receptor of DFB as an ABCC class
transporter. DFB-treatment and RNAi of a specific ABCC-type
transporter gene lead to identical phenotypes including loss of
chitin, loss of laminar architecture of the cuticle, and
mislocalization of CHS from its normal plasma membrane location to
intracellular
locations presumably by affecting vesicular
transport. Further, using an in vitro chitin synthesizing system
consisting of microsomes prepared from elytral tissue, which
exhibits all of the hallmarks of cuticular chitin-synthesizing
epidermal cells including sensitivity to DFB, further insights into
the mechanistic details of how this class of insecticides inhibits
chitin synthesis have been obtained.
Advisors/Committee Members: Subbaratnam Muthukrishnan.
Subjects/Keywords: Chitin
inhibitor;
Diflubenzuron; Molecular
target; ABC
transporter; Mode of
action
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kumari, M. (2015). The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/35784
Chicago Manual of Style (16th Edition):
Kumari, Meera. “The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron.” 2015. Doctoral Dissertation, Kansas State University. Accessed April 12, 2021.
http://hdl.handle.net/2097/35784.
MLA Handbook (7th Edition):
Kumari, Meera. “The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron.” 2015. Web. 12 Apr 2021.
Vancouver:
Kumari M. The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron. [Internet] [Doctoral dissertation]. Kansas State University; 2015. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/2097/35784.
Council of Science Editors:
Kumari M. The molecular
target and mode of action of the acylurea insecticide,
diflubenzuron. [Doctoral Dissertation]. Kansas State University; 2015. Available from: http://hdl.handle.net/2097/35784
Virginia Tech
30.
Pham, Ngoc Nhu.
Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti.
Degree: MSin Life Sciences, Entomology, 2016, Virginia Tech
URL: http://hdl.handle.net/10919/71699
► Mosquitoes affect human health worldwide as a result of their ability to vector multiple diseases. Mosquitocide resistance is a serious public health challenge that warrants…
(more)
▼ Mosquitoes affect human health worldwide as a result of their ability to vector multiple diseases. Mosquitocide resistance is a serious public health challenge that warrants the development of improved chemical control strategies for mosquitoes. Previous studies demonstrate the mosquito blood-brain barrier (BBB) to interfere with the target-site delivery and action of anticholinesterase chemistries. The ATP-binding cassette (
ABC) transporters are efflux proteins that assist in maintaining the BBB interface and serve as a first line of defense to mosquitocide exposures. To date, there are three subfamilies (
ABC -B, -C, -G) of
ABC transporters; however, knowledge of these chemistries interacting with mosquito
ABC transporter(s) is limited. Here, I report that tacrine and bis(7)-tacrine are relative non-toxic anticholinesterases at solubility limits; however, the addition of verapamil enhances toxicity of both tacrine and bis(7)-tacrine to mosquitoes. Verapamil significantly increases the mortality of mosquitoes exposed to tacrine and bis(7)-tacrine compared to the tacrine- and bis(7)- tacrine-only treatments. Tacrine and bis(7)-tacrine reduce acetylcholinesterase activity in mosquito head preparations compared to the untreated mosquitoes; however, the addition of verapamil significantly increases the anticholinesterase activity of tacrine and bis(7)-tacrine compared to the tacrine-and bis(7)-tacrine-only treatments. Tacrine and bis(7)-tacrine increase ATPase activity in Aedes aegypti at lower concentrations compared to that of verapamil (Fig. 3). The differential increase in ATPase activity suggests that tacrine and bis(7)-tacrine are more suitable substrates for
ABC transporter(s) compared to verapamil and, thus, provides putative evidence that
ABC transporter(s) is a pharmacological obstacle to the delivery of these anticholinesterases to their intended target site.
Advisors/Committee Members: Anderson, Troy D. (committeechair), Paulson, Sally L. (committee member), Brewster, Carlyle C. (committee member), Carlier, Paul R. (committee member), Li, Jianyong (committee member).
Subjects/Keywords: mosquito; tacrines; verapamil; acetylcholinesterase ATPase activity; ABC transporter
Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Pham, N. N. (2016). Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti. (Masters Thesis). Virginia Tech. Retrieved from http://hdl.handle.net/10919/71699
Chicago Manual of Style (16th Edition):
Pham, Ngoc Nhu. “Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti.” 2016. Masters Thesis, Virginia Tech. Accessed April 12, 2021.
http://hdl.handle.net/10919/71699.
MLA Handbook (7th Edition):
Pham, Ngoc Nhu. “Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti.” 2016. Web. 12 Apr 2021.
Vancouver:
Pham NN. Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti. [Internet] [Masters thesis]. Virginia Tech; 2016. [cited 2021 Apr 12].
Available from: http://hdl.handle.net/10919/71699.
Council of Science Editors:
Pham NN. Toxicological Analysis of Tacrines and Verapamil on the Yellow Fever Mosquito, Aedes aegypti. [Masters Thesis]. Virginia Tech; 2016. Available from: http://hdl.handle.net/10919/71699
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Open Access Theses and Dissertations
