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Project

Development of a Centre for Whole Genome Sequencing studies of Mycobacterium.

Tuberculosis (TB) is a global problem, with > 9 million cases annually and rising numbers of multi-drug resistant TB (MDR-TB). In the 1990's, IS6110 DNA fingerprinting revolutionized the study of Mycobacterium tuberculosis (MTB). Using this technique, I performed groundbreaking studies that proved exogenous reinfection, challenged the dogma that most TB cases are due to re-activation of latent infection, opposed the belief that most MDR-TB is acquired, and demonstrated mixed infection (NEJM 1999, JID 1999, Lancet 2000, AJCCRM 2005). The recent development of high-throughput, relatively low-cost whole genome sequencing (WGS) raises again the promise of significant gains in molecular epidemiology of MTB. Arriving at new paradigms however demands that inferences of WGS data on phylogeny, transmissibility, virulence and resistance are contextualized and integrated with clinical and demographic meta-data in large-scale studies to test the hypotheses generated by small-scale studies on isolates collected in low TB burden countries. As a clinical and molecular epidemiologist, I propose to establish and direct a multidisciplinary Centre for WGS studies of MTB at the University of Antwerp. The Centre will embed itself in the molecular microbiology laboratory of Prof Herman Goossens, who has substantial expertise in WGS research of pathogens other than MTB. The Centre will work in close collaboration with Prof Robin Warren of the South African Centre of Excellence for Biomedical Tuberculosis Research (CEBTR), Stellenbosch University. Access to the ~50,000 MTB strains in the CEBTR biobank will provide a unique opportunity for the Centre to perform molecular epidemiological MTB studies that address ground-breaking basic science and molecular epidemiological questions. To maximize the public health gains of WGS, we will focus on studies of MTB transmission dynamics in a high TB burden setting, the role of epistatis in emergence of drug resistance, MTB adaptation to drug pressure, and within-host MTB diversity.
Date:1 Oct 2016 →  30 Sep 2021
Keywords:TUBERCULOSIS, SEQUENCING
Disciplines:Public health care, Public health sciences, Public health services
Project type:Collaboration project