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PhD by Research Programme (Infection and Immunity)

Employer
Global Academy Jobs
Location
Singapore
Closing date
Jan 31, 2017

Job Details

Research Project Title: Elucidation of the Functional Roles of Lipid Metabolism During Mycobacterium-Host Interactions Using Systems-Based Approaches

Principal Investigator:

Assistant Professor Guan Xueli, LKCMedicine

Co-supervisor:

Associate Professor Eric Yap Peng Huat, LKCMedicine

Project Description:

Mycobacterium tuberculosis complex (MTBC), causative agent of tuberculosis, continues to be a threat to global health and economy, affecting billions of people. Astoundingly, this ancient bacterium has co-evolved with the human host and is a highly successful pathogen, threatening the world with untreatable tuberculosis, with the emergence of drug resistance. The cell biology of this intracellular pathogen has provided us with molecular information of host–pathogen interactions, yet, many questions remain to be solved. 

Mycobacterium lipid metabolism has received substantial attention because 60% of the dry weight of the bacterium is composed of lipids, which are the basic building blocks for biological membranes and reservoirs for energy storage, which are critical for growth and development. MTBC has evolved clever strategies to realign its metabolism using fatty acids as preferred carbon sources, and further able to hijack host metabolites, for its survival and persistence within the host. Critically, Mycobacterium lipids function as virulence factors, and the distinct enzymatic machineries from the host serve as existing as well as potential new drug targets, including the first line drug Isoniazid. However, biochemically, the precise lipid-requirement for this deadly pathogen remains poorly resolved, in part due to past limitations for the analysis of these metabolites. 

In this project, we will use a systems-based approach combining high-end lipidomics approaches and infection model which our Group has developed, transcriptomics, genomics and bioinformatics, with the aims to scrutinize the roles of lipids during mycobacterial infections. We will identify pathways critical for this intimate host-pathogen relationship. Cell-based assays, involving pharmacological intervention and genetic manipulation, will be performed to understand how modulation of lipid pathways affect the host-pathogen interactions and evaluate their relevance for drug target discovery as well as acquisition of drug resistance.


If you have questions regarding this project, please email the Principal Investigator, Assistant Professor Guan Xueli, at xueli.guan@ntu.edu.sg

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