Leishmania donovani upregulates host macrophage Argonaute 1 to persist inside infected host, and quantitative proteomic analysis of RNA-induced silencing complex isolated from infected host
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Moradimotlagh, Atieh
issued: 2023-05-08T15:56:32Z
issued: 2023
related degree: Master of Science - MSc
degree grantor: University of British Columbia
description: Leishmania is a protozoan parasite that causes a wide range of diseases collectively known as leishmaniasis, which differ in symptoms and severity throughout various clinical forms, including cutaneous, mucocutaneous, and visceral. It is well established that Leishmania exploits the cell biology of host macrophages for successful infection and persistence inside the host. Identification and characterization of Leishmania interactions with host cellular proteins/pathways and the functional consequences of these interactions can pave the way to develop novel anti-leishmanial strategies targeted at these interactions. To date, our understanding of the molecular mechanisms associated with the pathogenicity of Leishmania infection is still limited. RNA silencing pathways—collectively referred to as RNA interference—participates in the regulation of various biological processes in most eukaryotic cells. It is becoming increasingly clear that several intracellular pathogens target host cell RNA interference pathways to promote their survival. In this study, we investigated the potential role of host macrophage Argonautes in Leishmania pathogenesis and found Leishmania macrophage Argonaute 1 (Ago1) was selectively and significantly more abundant than that of non-infected control, suggesting that Ago1 plays a role in pathogenicity. In fact, siRNA-mediated downregulation of Ago1 enhanced Leishmania clearance from infected host cells, linking macrophage Ago1 to Leishmania virulence. To investigate the mechanisms of host Ago1 in Leishmania pathogenesis, we employed whole proteome approach which showed that expression of several previously reported Leishmania pathogenesis-related proteins were dependent on the level of macrophage Ago1. Moreover, detailed biochemical analysis showed that Leishmania modulated host RNA-Induced Silencing Complex (RISC) composition during infection, strongly suggesting macrophage RISC targeting. Strikingly, Leishmania proteins were detected as part o…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/84581
note: Leishmania donovani upregulates host macrophage Argonaute 1 to persist inside infected host; and quantitative proteomic analysis of RNA-Induced Silencing Complex isolated from infected host by Atieh Moradimotlagh BSc, University of Tehran, 2014 MSc, University of Tehran, 2018 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in The Faculty of Graduate and Postdoctoral Studies (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2023 © Atieh Moradimotlagh, 2023 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Leishmania donovani upregulates host macrophage Argonaute 1 to persist inside infected host; and quantitative proteomic analysis of RNA-Induced Silencing Complex isolated from infected host submitted by Atieh Moradimotlagh in partial fulfilment of the requirements for the degree of Master of Science in Experimental Medicine Examining Committee: Dr. Neil Reiner, Professor, Faculty of Medicine, UBC Supervisor Dr. Laura Sly, Professor, Faculty of Medicine, UBC Supervisory Committee Member Dr. Vince Duronio, Professor, Faculty of Medicine, UBC Supervisory Committee Member Dr. Robert McMaster, Professor, Faculty of Medicine, UBC Additional Examiner iii Abstract Leishmania is a protozoan parasite that causes a wide range of diseases collectively known as leishmaniasis, which differ in symptoms and severity throughout various clinical forms, including cutaneous, mucocutaneous, and visceral. It is well established that Leishmania exploits the cell biology of host macrophages for successful infection and persistence inside the host. Identification and characterization of Leishmania interactions with host cellular proteins/pathways and the functional consequences of these interactions can pave the way to develop novel anti-leishmanial strategies targeted at these interactions. To date, our u…
has type: Thesis/Dissertation
date issued: 2023-05
is shown at: 10.14288/1.0432032
language: eng
degree discipline: Experimental Medicine
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
contributor: Reiner, Neil E.
type: Text
identifier URI: http://hdl.handle.net/2429/84581