The SAMRC Centre for Tuberculosis Research is housed within the Division of Molecular Biology and Human Genetics at Stellenbosch University, which also hosts the Centre of Excellence for Biomedical Tuberculosis Research, and three prestigious NRF SARChI chairs Animal TB (Prof M Miller), Mycobactomics (Prof S Sampson) and TB Immunology (Prof G Walzl). The Centre is an intramural research unit of the SAMRC partnered with Stellenbosch University. The focus is on tuberculosis research, with an emphasis on the South African situation. The Centre aims to improve the health status and quality of life of the population through the generation of new knowledge and apply that to health oriented research aimed at reducing incidence and prevalence by diagnosing and treating appropriately and by measures aimed at prevention. The research conducted within the Centre spans basic to translational, aligning with the National Development Plan, as well as UN Sustainable Development Goal 3 - Ensure healthy lives and promote well-being for all at all ages.
Animal TB - click to view more information
The Animal TB research programme takes a multi-pronged approach to improving knowledge of the epidemiology, pathogenesis and immunology of members of the Mycobacterium tuberculosis complex (MTBC). This includes investigating the role of host, pathogen and environmental factors influencing risk of infection and development of disease; the genetic diversity of mycobacterial pathogens affecting wildlife and domestic animals; and comparative immunological responses, with a focus on the development of diagnostic assays. We use a “One Health” approach to investigate interactions and interfaces affecting TB in multi-host ecosystems, working with conservation organisaations, veterinarians, epidemiologists, human TB experts, and other professionals. Our current research projects involve a diverse array of species including rhinoceros, elephant, meerkats, mongooses, lions, warthogs, hyenas and wild dogs. Led by the NRF SARChI chair in Animal TB, Prof. Miller, and senior researcher, Dr. Parsons, this programme incorporates a continuum of basic to applied research both in the laboratory and field. Research outputs will inform evidence-based management and policies on disease control.
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Modern molecular experiments using massively parallel techniques produce tremendous volumes of data. The sheer volume can obscure valuable information. The bioinformatics team maximises the information yield from these experiments. Prof. Tabb specialises in the development of data analysis pipelines starting from instrument outputs, with a particular emphasis on biological mass spectrometry. Prof. Tromp focuses on experiment design, statistical evaluation, and machine learning approaches, with special applications in high-throughput sequencing. Prof. van der Spuy specialises in the design and statistical analysis of complex studies. Together, they lead the South African Tuberculosis Bioinformatics Initiative (SATBBI).
Clinical Mycobacteriology and Epidemiology
The Clinical Mycobacteriology and Epidemiology (CLIME) group focuses on three key areas of research into tuberculosis. These include:
- the diagnosis of tuberculosis and drug resistance
- the study of patient infectiousness and tuberculosis transmission
- the microbiome of tuberculosis patients.
Members of the CLIME group have diverse backgrounds, and include fundamental scientists and clinical trials field staff. The group maintains close links with both the City and Provincial Departments of Health, with whom they closely conduct studies, as well as Tygerberg General Hospital. Research done by members of the group is cited in global and national policy documents, and is frequently presented at international fora.
Ongoing projects within the group include:
- Field evaluations of the new Xpert Ultra, MTBDRsl, and urine LAM tests for pulmonary and extrapulmonary TB
- “Hacking” the Xpert cartridge to use it as a tool for DNA extraction for further genotypic drug susceptibility testing
- Sampling the cough aerosol of different types of TB patients, and studying the impact of novel drugs and different respiratory manoeuvres on patient infectiousness
- Investigating the physiological state and airborne survival of different Mycobacterium tuberculosis clinical isolates
- Studying the role of the microbiome in predicting TB treatment response and relapse
Members of the group currently receive funding from the South African National Research Foundation, the South African Medical Research Council, the British Royal Society, the Harvard Medical Centre for Global Health Delivery, and the European and Developing Countries Clinical Trials Partnership. CLIME also partners with a variety of international commercial and non-academic institutions to conduct contract research.
CLIME is always looking to work with talented students and staff and potential collaborators. If you are interested in doing so please contact Grant on email@example.com.
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Clinical TB Research
The clinical team of the Department of Molecular Biology and Human Genetics works actively on observation studies and clinical trials concerning tuberculosis, HIV, diabetes and parasites. The team conduct routine and special investigations, including bronchoscopies and PET/CT’s. They also recruit volunteers and gather valuable data and specimen used for fundamental and translational research and new diagnostic discovery. Their goal is to discover improved tools to prevent, diagnose, treat and monitor treatment responses. The scale of the projects range from post-graduate student level to large international consortia.
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Comparative Genomics, Diagnostics and Drug Resistance
Our group focuses on comparative genomics by whole genome sequencing (WGS), transcriptomics using RNA-seq, and proteomics, allowing us to investigate the epidemiology and evolution of Mycobacterium tuberculosis. We are currently building a genome sequence bank, comprising thousands of sequences of local clinical isolates – complementing our vast sample bank. These sequences allow us to scrutinize the local epidemic in terms of outbreak investigations, within-patient evolution of drug-resistance, transmission and discovering novel drug-resistance causing mutations. By combining WGS with RNA-seq or proteomics we are able to determine the impact of drug resistance on the physiology of Mycobacterium tuberculosis. We are also involved in the development and evaluation of rapid molecular diagnostics for the detection of drug resistance that are based on information generated through molecular epidemiology studies/data, helping to tailor diagnostics to the local epidemic.
Visit the The Centre of Whole Genome Sequencing of Mycobacterium Tuberculosis Website
Host Pathogen Mycobactomics
Our overall research goal is to gain a better understanding of how the pathogen Mycobacterium tuberculosis interacts with its host to cause disease. To achieve this, we use molecular mycobacteriology and in vitro infection models together with data-rich methodologies such as whole genome sequencing, transcriptomics, and proteomics. These methods are underpinned by computational approaches. Specific research areas include advancing our understanding of: (a) TB host-pathogen interactions, with a particular focus on persistent mycobacteria, (b) biology of drug resistant strains of M. tuberculosis, and (c) PE/PPE proteins of M. tuberculosis.
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Immunology Research Group
The main focus of the Immunology Research Group is the identification of immune biomarkers for use in trials for novel diagnostics, new treatment regimens and vaccines. We work with several international consortia and with several US, European and African partners on large cohorts of participants, searching for biomarkers of TB infection and disease. We also focus on immune-endocrine interactions and particularly the role of Type 2 Diabetes Mellitus in TB susceptibility. Our laboratory team processes a range of sample types from participants, including serum, urine, saliva, sputum, exhaled breath condensate, broncho-alveolar lavage, pleural fluid and cerebrospinal fluid. The Immunology Research Group is passionate about education in immunology and produces several doctoral, masters and honours degrees annually.
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Our research is aimed at better understanding the physiology of Mycobacterium tuberculosis. We utilise a combination of mycobacterial genetics, molecular biology and biochemistry to study the pathogen’s metabolism. A major focus of our work is studying the iron-sulphur (Fe – S) cluster biosynthetic pathway in mycobacteria, and elucidating the role that this pathway plays in drug susceptibility and pathogenesis of M. tuberculosis. The long-term goal of characterising this pathway is to identify novel anti-TB drug targets and proteins that have diagnostic potential.
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The TB Drugs group has three main research focus areas:
- Identify factors involved in the survival of mycobacteria in mouse and human macrophages employing transcriptomic and proteomic analyses. These targets are further investigated in animal infection models with the long-term aim of developing novel host-directed therapeutics.
- Investigate unique metabolic pathways in M.tb through metabolomic analyses and generating specific M.tb mutants to evaluate potential targets for drug intervention. Pathways of specific interest are the ergothioneine/mycothiol pathways and those identified to contain kinase/synthetase reactions that are either only prokaryotic in nature or specific to M.tb. These enzymes are being cloned, expressed and purified to be included into primary inhibitor screens as part of a chemical biology approach to identifying novel drug targets.
- Test lead compounds against M.tb in vitro and ex vivo in collaboration with local and international institutes.
TB Host Genetics
Why do some people get TB and others not? Most infected people never develop the disease, and our focus is on the genetic underpinnings of this inter-individual variation. The immune response genes play a major role and we aim to identify the unknown host genes controlling resistance. We use our very large sample bank and databank together with sequencing technologies, state-of-the-art genotyping and bioinformatics analysis methods to find genes influencing susceptibility to TB and primary immunodeficiencies in a South African population with a very high incidence. We also take the work to the cellular level by studying the functional pathways of the genes discovered, using our very large sample bank and databank. We also study genetic diversity in sub-Saharan Africa to further assist research in populations of African descent, which will be important in selecting appropriate and efficacious TB vaccines for these populations.
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Contact details of all Research Areas