Project: Novel biomarkers predictive of susceptibility and treatment response in patients with MDR-TB

Acronym	DTBD (Reference Number: TMA 2015 SF - 1043)
Duration	01/04/2017 - 31/03/2022
Project Topic	The proposed Senior Fellow, Professor Keertan Dheda, currently heads up the Lung Infection and Immunity Unit (LIIU) at the University of Cape Town. Professor Dheda returned to Africa in 2008 after undertaking training in respiratory medicine in the UK and completing a PhD at University College London. He is now seeking to consolidate his senior researcher position by: i) Acquiring more advanced and formal management and leadership skills, and training. ii) Mentoring the next generation of African researchers equipped to deal with “omic” technologies and data including genomics, transcriptomics and metabolomics. iii) Developing research capacity through establishing a genome sequencing analysis platform that will include the training of PhD students and post-docs able to analyse data derived from 21st century technologies including whole genome and RNA sequencing, and develop the relevant bioinformatic pipelines. Training of African scientists in this area remains a priority. The applicant proposes to achieve these broad objectives in 3 ways: i) Through student teaching, training and mentoring; ii) Through attending professional developmental courses and seminars focusing on advanced project and financial management, and intellectual property creation and management; iii) Through acquiring hands-on experience in bioinformatics analytical pipelines through short-term sabbatical visits and traineeships. The proposed mentorship and personal developmental activities will be nested within the NExT RCT, a South African MRC-funded (€2 million) randomised control trial that is evaluating a new 6-month injection-free regimen for MDR-TB (PI= Professor Dheda). Within the context of NeXT three specific laboratory-based sub-studies (the focus of the current proposal) will be undertaken, which will form the basis of student training and mentorship (see Figure 1 for the project overview). Thus, the Fellowship if NOT to conduct a clinical trial (this is already funded and on-going) but to use the bio-banked samples to conduct student-led laboratory-based studies. i) The first study seeks to evaluate a package of treatment response biomarkers for MDR-TB. Currently planned controlled trials for MDR-TB are prolonged and costly largely because of the lack of outcome-specific predictive biomarkers. ii) The second sub-study will undertake next generation whole-genome-sequencing using biobanked isolates. PhD student Jason Limberis will identify mutations associated with second-line drug resistance. Dr. Boitumelo Fanampe, a post-doc, will in parallel investigate methods to allow sequencing-related information to be derived directly from clinical samples. Thus, in summary, these are critical studies that will fill an unmet need that have the capability of having far reaching implications for clinical practice.
Network	EDCTP2
Call	Training and Mobility Awards: Senior Fellowships

Project partner

Number	Name	Role	Country
1	University of Cape Town Lung Institute (Pty) Ltd	Coordinator	South Africa