Novel approaches to treating and preventing malaria
department or school: Applied Science, Faculty of
department or school: Chemical and Biological Engineering, Department of
data provider: DSpace
degree campus: UBCV
creator: Nogueira Varela, Julia
issued: 2020-06-30T07:00:00Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Malaria presents a severe economic and healthcare burden for the developing world. Recent efforts to reduce the incidents of malaria-associated deaths achieved some success, but drug resistance is increasing and the number of drugs available to treat the diseases is thinning. The current thesis seeks to advance two complementary strategies to develop platform solutions to treat and prevent malaria. First, we applied cheminformatics to assess the chemical space of anti-malarial drugs to identify promising scaffolds. Open-source tools were used to analyze the scaffolds of candidates and approved anti-malarial drugs. Our scaffold-centric analysis reveals that the anti-malarial chemical space is disjointed and segregated into few dominant structural groups with these structures being distributed according to Paretos’ principle. This structural convergence can potentially be exploited for future drug discovery by incorporating it into bioinformatics workflows. This could be used to predict new combination therapies and areas for the development of new molecules. Our second strategy seeks to develop a better tool for repellent discovery; repellent usage to prevent mosquito bites is a safe way to control these infections. The current methods for repellent screening are time consuming. The olfactory pathway involves odorant receptors that form a heterodimeric ion channel with an odorant receptor co-receptor (Orco) and a switching odorant receptor (OR). The heterologous expression of these proteins in Xenopus-oocytes and HEK293 cells, have suggested that the Orco-OR complex is functional. While these hosts have permitted significant discoveries, they have slow growth rates and extensive handling requirements, which make them unwieldy for high-throughput screens. We sought to develop high-throughput repellent screens by reconstructing this olfactory pathway into a simpler host (Pichia pastoris) with the Orco receptor. The Anopheles gambiae Orco protein was successfully expres…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/70739
note: NOVEL APPROACHES TO TREATING AND PREVENTING MALARIA by Julia Nogueira Varela B.Sc., State University of Campinas, 2011 M.Sc., State University of Campinas, 2013 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Chemical and Biological Engineering) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) June 2019 © Julia Nogueira Varela, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: NOVEL APPROACHES TO TREATING AND PREVENTING MALARIA submitted by Julia Nogueira Varela in partial fulfillment of the requirements the degree of Doctor of Philosophy In Chemical and Biological Engineering Examining Committee: Dr. Vikramaditya G. Yadav, Chemical and Biological Engineering Supervisor Dr. Charles A. Haynes, Chemical and Biological Engineering Supervisory Committee Member Dr. Filip VanPetegem, Biochemistry and Molecular Biology Supervisory Committee Member Dr. Karen C. Cheung, Electrical and Computer Engineering University Examiner Dr. Susan A. Baldwin, Chemical and Biological Engineering University Examiner Additional Supervisory Committee Members: Dr. John Smit, Microbiology and Immunology Supervisory Committee Member Dr. James Piret, Chemical and Biological Engineering Supervisory Committee Member iii Abstract Malaria presents a severe economic and healthcare burden for the developing world. Recent efforts to reduce the incidents of malaria-associated deaths achieved some success, but drug resistance is increasing and the number of drugs available to treat the diseases is thinning. The current thesis seeks to advance two complementary strategies to develop platform solutions to treat and prevent malaria. First, we applied cheminformatics to assess the chemical space of anti-malarial drugs to identify promising scaffolds. Open-source tools were used to analy…
has type: Thesis/Dissertation
date issued: 2019-09
is shown at: 10.14288/1.0379537
language: eng
degree discipline: Chemical and Biological Engineering
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/70739