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You searched for subject:(host directed therapy). Showing records 1 – 3 of 3 total matches.

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Macquarie University

1. Hortle, Elinor. ENU mutagenesis and the quest for a malaria host-directed therapy.

Degree: 2015, Macquarie University

Empirical thesis.

Bibliography: pages 129-152.

Chapter 1. Literature review  – Chapter 2. Experimental procedures  – Chapter 3. MR149372 blood phenotype  – Chapter 4. MR149372 malaria  – Chapter 5. RBC10  – Chapter 6. Final discussion and conclusions.

Malaria is a disease of global concern, which causes over 800,000 deaths every year. Due to the rapid emergence of parasite drug resistance, ongoing control of malaria requires the urgent development of new anti-malarials that will have a prolonged life span. Genetic polymorphisms that provide natural resistance to malaria have existed in human populations for thousands of years without losing their efficacy. This suggests a possible new treatment strategy; drugs can be used to mimic the protective effects of such polymorphisms, in what is known as host-directed therapy (HDT). It is hoped that HDT will be able to effectively treat malaria without driving drug resistance. An ENU mutagenesis screen was established in mice to identify novel genes mediating host resistance to malaria, and to thereby uncover potential drug targets for an anti-malarial HDT. Two mutant mouse lines were investigated: MR149372, in which an over-activation of the enzyme AMPD3 causes striking resemblance to P. Chabaudi parasitaemia through high RBC turnover; and RBC10, in which an over-activation of the transporter KCC1 causes resistance to the development of cerebral malaria and modulation of the inflammatory response during P. berghei infection.

Through the work in this thesis, novel insight has been gained into the role of AMPD3 in determining red blood cell half-­‐life, the effect of altered purine balance on intra-­erythrocytic parasite growth, and the host factors affecting the immune response to malaria infection. Moreover, potential novel drug targets have been identified both for lengthening the life span of blood stored for transfusion, and for treating cerebral malaria.

1 online resource (xiv, 163 pages) illustrations (some colour)

Advisors/Committee Members: Macquarie University. Australian School of Advanced Medicine.

Subjects/Keywords: Malariotherapy; Malaria  – Gene therapy; Antimalarials  – Research; Mutagenesis; malaria; host-directed therapy

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APA (6th Edition):

Hortle, E. (2015). ENU mutagenesis and the quest for a malaria host-directed therapy. (Doctoral Dissertation). Macquarie University. Retrieved from http://hdl.handle.net/1959.14/1068652

Chicago Manual of Style (16th Edition):

Hortle, Elinor. “ENU mutagenesis and the quest for a malaria host-directed therapy.” 2015. Doctoral Dissertation, Macquarie University. Accessed October 23, 2019. http://hdl.handle.net/1959.14/1068652.

MLA Handbook (7th Edition):

Hortle, Elinor. “ENU mutagenesis and the quest for a malaria host-directed therapy.” 2015. Web. 23 Oct 2019.

Vancouver:

Hortle E. ENU mutagenesis and the quest for a malaria host-directed therapy. [Internet] [Doctoral dissertation]. Macquarie University; 2015. [cited 2019 Oct 23]. Available from: http://hdl.handle.net/1959.14/1068652.

Council of Science Editors:

Hortle E. ENU mutagenesis and the quest for a malaria host-directed therapy. [Doctoral Dissertation]. Macquarie University; 2015. Available from: http://hdl.handle.net/1959.14/1068652


Australian National University

2. Huang, Hong Ming. Complex roles ankyrin-1 plays in malaria infections .

Degree: 2016, Australian National University

Despite the numerous interventions employed in the past few decades, malaria remains one of the most lethal diseases affecting millions of people worldwide. This is partly due to the emergence of resistance to the current parasite-targeted antimalarials. In contrast, erythrocytic genetic mutations have been conferring malaria protection in humans for thousands of years without losing their effectiveness. This presents a new therapeutic approach to mimic these genetic mutations to treat malaria, known as host-directed therapy (HDT), which requires further understanding of host-parasite interactions to identify potential HDT drug targets. One such HDT target is the erythrocytic cytoskeleton, which parasites rely on for their survival. Ankyrin-1 (Ank-1) is one of erythrocytic cytoskeleton proteins, which has been associated with hereditary spherocytosis (HS) in humans. This thesis investigates the roles of Ank-1 in malaria infections using mouse models and blood from HS patients. Mice with Ank-1 mutations were found to exhibit phenotypes similar to human HS patients and are protected against malaria via multiple mechanisms, suggesting that Ank-1 plays a complex role in malaria infections. These mechanisms are heavily influenced by the nature of Ank-1 mutations, which is further confirmed in human HS erythrocytes. This thesis also explores the possibility of using the ankyrin-spectrin interaction as a HDT target. Results show that the disruption of this interaction has little effect on the health of the mice, while conferring significant resistance towards malaria, thus enabling the use of high throughput screening (HTS) for drug discovery. To summarise, this thesis highlights the complex interactions between the erythrocyte cytoskeleton and malarial parasites, as well as providing insights into the heterogeneous protective role of Ank-1 in mediating malaria resistance. It also raises the possibility of using erythrocytic cytoskeletal proteins as HDT drug targets, which could potentially yield novel therapies for malaria in the future.

Subjects/Keywords: Malaria; Genetics; host-parasite interactions; host-directed therapy; ankyrin-1; allelic heterogeneity; erythrocyte cytoskeletons

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Huang, H. M. (2016). Complex roles ankyrin-1 plays in malaria infections . (Thesis). Australian National University. Retrieved from http://hdl.handle.net/1885/117238

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):

Huang, Hong Ming. “Complex roles ankyrin-1 plays in malaria infections .” 2016. Thesis, Australian National University. Accessed October 23, 2019. http://hdl.handle.net/1885/117238.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Huang, Hong Ming. “Complex roles ankyrin-1 plays in malaria infections .” 2016. Web. 23 Oct 2019.

Vancouver:

Huang HM. Complex roles ankyrin-1 plays in malaria infections . [Internet] [Thesis]. Australian National University; 2016. [cited 2019 Oct 23]. Available from: http://hdl.handle.net/1885/117238.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Huang HM. Complex roles ankyrin-1 plays in malaria infections . [Thesis]. Australian National University; 2016. Available from: http://hdl.handle.net/1885/117238

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


University of KwaZulu-Natal

3. [No author]. Cellular therapy in Tuberculosis.

Degree: 2015, University of KwaZulu-Natal

Abstract available in pdf.

Subjects/Keywords: Tuberculosis.; MDR-TB.; Host directed therapy.; M.tuberculosis.; Inflammation.; Mesenchymal stromal cells.; T-cells.; Cancer.; HDT.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

author], [. (2015). Cellular therapy in Tuberculosis. (Thesis). University of KwaZulu-Natal. Retrieved from http://dx.doi.org/10.1016/j.ijid.2015.01.016

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):

author], [No. “Cellular therapy in Tuberculosis. ” 2015. Thesis, University of KwaZulu-Natal. Accessed October 23, 2019. http://dx.doi.org/10.1016/j.ijid.2015.01.016.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

author], [No. “Cellular therapy in Tuberculosis. ” 2015. Web. 23 Oct 2019.

Vancouver:

author] [. Cellular therapy in Tuberculosis. [Internet] [Thesis]. University of KwaZulu-Natal; 2015. [cited 2019 Oct 23]. Available from: http://dx.doi.org/10.1016/j.ijid.2015.01.016.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

author] [. Cellular therapy in Tuberculosis. [Thesis]. University of KwaZulu-Natal; 2015. Available from: http://dx.doi.org/10.1016/j.ijid.2015.01.016

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.