TB Genomics
Welcome to Stellenbosch University

Division of Molecular Biology and Human Genetics

​​​​​​​​TB GENOMICS

​​​​​​​​​​​​​​​​​TEAM MEMBERS

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Prof Robin Warren

​​SAMRC Centre for Tuberculosis Research Unit Director

Head of TB Genomics Research Group

rw1@sun.ac.za

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Prof Rob Warren obtained a PhD degree in Biochemistry from the University of Cape Town in 1995 and subsequently joined the Department of Medical Biochemistry, Stellenbosch Universit. He was appointed as Professor in the Division of Molecular Biology in 2015 and subsequently a distinguished Professor. Under his guidance the study of the molecular epidemiology of Mycobacterium tuberculosis in a high incidence setting (Cape Town, South Africa) was brought to the forefront of international tuberculosis research. This study now represents the largest molecular epidemiological data set in the developing world and has been referred to as a national heritage. Much of this work has provided new understanding, which has allowed long standing dogmas to be challenged. He has published more than 230 papers in international peer reviewed journals in the fields of molecular epidemiology, drug resistance and bacterial evolution since 1996. These studies have given him excellent experience in managing grant-related outputs and established infrastructure for conduct of ongoing research. 

In January 2017, He was appointed as the Unit director for the South African Medical Research flagship Centre for Tuberculosis Research which is housed within the Division. His current research focuses on: 1) the disease dynamics of drug sensitive and M(X)DR-TB in the Western Cape, 2) the development of novel diagnostics which are applicable to the developing world, 3) discovery of the mechanisms whereby drug resistance develops, 4) speciation of mycobacteria causing disease in humans and animals, 5) application of novel methods to improve the speed of diagnosing smear positive disease, 5) host-pathogen compatibility, 6) identification of highly pathogenic strains of M. tuberculosis, 7) pathogen evolution and 8) mycobacterial epigenetics. He co-developed a whole-genome sequence analysis group with the aim to enhance the resolution of molecular epidemiological interpretation to impact on treatment and policy.​


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Prof Elizabeth Streicher

​​Senior Scientist

lizma@sun.ac.za

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Prof Lizma Streicher joined the Division of MBHG in 2001 as a postgraduate student, followed by a postdoctoral fellowship, research scientist and currently as a professor. She established a culture bank of drug-resistant M. tuberculosis isolates from patients from the Western Cape Province. Lizma continues to manage this resource, which currently has more than 55000 TB cultures. This very valuable resource forms the basis for various student research and collaborations that contributed significantly to our current understanding and molecular epidemiology, exogenous reinfection, dual infections, and mechanisms and the spread of drug-resistant TB. A special area of interest is the acquisition of drug resistance and specifically the influence of hetero-resistance on molecular-based drug resistance diagnostics.


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Dr Marisa Klopper

​​Researcher

marisat@sun.ac.za

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Dr Marisa Klopper obtained her PhD degree in Molecular Biology at Stellenbosch University in 2015. She used whole genome- and transcriptome analysis to study drug-resistant tuberculosis in the Eastern Cape, South Africa, showing that an endemic strain of tuberculosis has repeatedly acquired resistance to all standard first- and second-line drugs and is spreading in such highly resistant forms. Her study of isoniazid mono resistance in the region has revealed the complexity of accurately diagnosing this form of tuberculosis. She is also interested in the biology of compensatory mechanisms and the role of iron and lipids in virulence and is supported by the EDCTP2 and the European Union for this work (TMA2017CDF-1885). Additionally, she collaborates with SU Electronic Engineering and the CLIME group of MBHG to investigate the use of cough sound analysis in diagnosis of TB and COVID-19.​​ 


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Dr Melanie Grobbelaar

​​Research Scientist

melgrob@sun.ac.za

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Dr Melanie Grobbelaar is interested in determining how different resistance-conferring rpoB mutations alter the function of RNA polymerase, how such mutants respond to external stressors, and whether the combination of these events alters fitness and the propensity to acquire resistance using qPCR and RNA-seq. She started her MSc in 2010 in the Division of MBHG. Her PhD centered around the transcriptomic effect of rifampicin on different mono-resistant isolates. Melanie was awarded an NIH grant for her postdoctoral work on adaptation, fitness, and resistance in rifampicin-resistant M. tuberculosis.



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Dr Nabila Ismail

​​Research Scientist

nabilai@sun.ac.za

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Dr Nabila Ismail's current research focuses on drug-resistance mechanisms; with a strong focus on bedaquiline resistance; mutations outside of canonical regions impacting drug resistance and uncovering these using WGS. She is actively involved in administration for all research and clinical studies within the group. Nabila has been with the TB Genomics Research Group since 2019. She achieved all three of her BSc, BSc (Hons) and MSc degrees in Biochemistry cum laude from the University of Pretoria and was actively involved in WGS of isolates from the National Drug Resistance Survey during her time at the NICD Centre for Tuberculosis




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Dr Taime Sylvester

​​Consultant Scientist

tashnicao@sun.ac.za

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Dr Taime Sylvester joined the Division of MBHG in 2014 when she started her PhD in Molecular Biology, focusing on characterizing the immune response of African lions to Mycobacterium bovis infection. Before joining Stellenbosch University she did her undergraduate training in Biomedical Technology at the Cape Peninsula University of Technology. Here she also completed her Masters in Biomedical Technology, focusing on evaluating the cardio-protection of kolaviron in ischaemia-reperfusion. In 2018, Taime joined Prof Rob Warren's research group as a postdoctoral fellow, where she aims to investigate the molecular epidemiology of tuberculosis in Namibia. 


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Felicia Wells

​​Research Assistant

fbwells@sun.ac.za

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Felicia Wells joined the Division of MBHG as a sequencing assistant in 2020. Her current research focuses on culture-free or early detection of TB infection and resistance profile information using whole genome sequencing technologies. Felicia achieved her degrees in BSc Molecular Biology and Biotechnology, BSc (Hons) in Biochemistry and MSc in Biochemistry at the University of Stellenbosch. During her MSc degree, she worked as a research assistant at the Department of Horticulture in testing different packaging materials that prevent ethylene damage and several mixed flower trails to determine shelf life and water uptake. During this time, she also assisted with GC-MS analyses for PhD students and postdocs at CAF GC-MS under the supervision of Mr. William Arries (Supervisor) and Mr. Lucky Mokwena (Manager).


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Jennifer Williams

​​Research Assistant

williamsj@sun.ac.za


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Jennifer's interest in antimicrobial resistance started in 2016 during her honours year at the North-West University, where she focussed on detecting kanamycin resistance-conferring genes. She completed her MSc in pharmaceutical sciences with her project, where she compared and evaluated molecular based TB drug resistance detection methods. During her studies, she worked as a laboratory demonstrator, completed a two-year internship at the Preclinical Drug Development Platform, and more recently, worked as an assistant in a pharmacy. She joined TB Genomics research group as a research assistant in November 2022 and is currently involved in a targeted sequencing-based evaluation study. 


​​​​​​​​​​​​​​​​​POSTDOCTORAL RESEARCHERS

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Dr Anzaan Dippenaar

​​Postdoctoral Researcher

anzaan.dippenaar@uantwerpen.be

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Dr Anzaan Dippenaar has been a member of the TB Genomics group since 2011, first as a PhD student and later as a post-doctoral research fellow and member of the Tuberculosis Omics Research (TORCH) consortium. She is interested in using Next-Generation sequencing approaches to investigate the microevolution of M. tuberculosis during transmission, the mycobacterial genomics of treatment response during tuberculosis disease, and to explore the genomic characteristics of various mycobacterial strains causing tuberculosis in a variety of animal host species. As of July 2020, she works as part of the Antwerp-based team of the TORCH consortium. 

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Dr Shatha Omar

​​Postdoctoral Researcher

shatha@sun.ac.za

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Dr Shatha Omar joined the Division of MBHG as a post-doctoral fellow in 2019. Her current research focuses on genetic characterization of NTM and their impact on macrophages during coinfection with M. tuberculosis. Shatha finished her Masters in 2008 determining the relationship between heat shock proteins (HSP's) and cell cycle regulator's proteins. She completed her PhD at the University of Cape Town, assessing the relationship between in vivo viral outgrowth in HIV-1 subtype C dual-infected individuals and Env entry efficiency, and to identify functional determinants of viral fitness as​ novel targets for drug and vaccine design. ​ 



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Dr​ Johannes (Hanno) Loubser​​

​​Postdoctoral Researcher

jloubser@sun.ac.za

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Dr Hanno Loubser is a molecular biologist with special interest in biotechnology, genetics, microbiology and bioinformatics. Since 2020, he is a postdoctoral researcher with the TB Genomics research group, where he is involved in next-generation sequencing analysis of MTBC. His projects of interest include the transmission dynamics of TB contacts, unknown variants of ethionamide resistance, within-host microevolution of MDR-TB, the role of DNA methylation in drug resistance, optimizing nanopore sequencing for TB diagnostics, standardization of bioinformatic pipelines for MTBC epidemiology. He is also very passionate about capacity building and teaching.​ 



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Dr Nandi Niemand​

​​Postdoctoral Researcher

nniemand@sun.ac.za

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Dr Nandi Niemand obtained her PhD in Molecular Biology and Human Genetics, focussing on mycobacterial physiology, investigating, and characterizing the role of a novel protein involved in the iron-sulfur cluster biogenesis system. She joined the TB Genomics group as part of her postdoctoral fellowship and primarily focuses on a study titled “Transmission of tuberculosis among illicit drug use linkages”, which aims to evaluate the proportion of TB c​ases derive from a recent transmission and define mechanisms responsible for efficient transmission in this population. In addition, she is also involved in the in vivo evaluation and characterization of single nucleotide polymorphism mutations and their association with phenotypic bedaquiline resistance.​ ​



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Dr Emilyn Costa Conceicao

​​Postdoctoral Researcher​

emilyncosta@sun.ac.za

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Dr Emilyn Costa Conceicao joined the Division of MBHG as a postdoctoral fellow in 2021. Her current research focuses on personalized medicine through WGS as part of “Sequencing Mycobacteria and Algorithm-Determined Resistant Tuberculosis Treatment (Smartt) Trial”. Emilyn is a Biologist (Federal University of Para), holding a masters degree in Infectious Disease (State University of Para) and PhD in Microbiology (Federal University of Rio de Janeiro/Paris-Sud University). Emilyn has experience in clinical trials and routine diagnostics with a focus on molecular biology applied to MTBC, NTM and Mycobacterium leprae. She is interested in epidemiology, genomics, drug-resistance, bioinformatics and science education​.


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Dr Brendon Mann

​​Postdoctoral Researcher​

bcmann@sun.ac.za


 


Dr Brendon joined the Division of MBHG as a postdoctoral fellow in 2021. He obtained his BSc Honours degree in environmental sciences, and MSc degree in Microbiology at the North-West University of Potchefstroom, working on environmental antimicrobial resistance. He did his PhD in Pharmaceutical Sciences at the DSI/NWU Preclinical Drug Development Platform (PCDDP) also at the North-West University, focussing on the human respiratory microbiome and its response to tuberculosis treatment, while also working on the development of a novel molecular TB diagnostic system. His current focus is to assess in-host M. tuberculosis genomic diversity to determine how this relates to treatment response and oversees the development of laboratory protocols for M. tuberculosis cellular and DNA enrichment from direct patient samples.​ ​


STUDENTS​

Lizma_Streicher.jpg​Justice Tresor N Ngom

​​Doctoral candidate​​

justicengom@sun.ac.za

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Project Description: Justice’s project is based on using the Next-generation Sequencing (NGS) method: WGS to decipher the impact of changes in treatment strategies on the XDR-TB population structure in the Western Cape Province over time.





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Janré Steyn

​​Doctoral candidate​​

janre@sun.ac.za​

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Project Description: To evaluate a targeted sequencing-based approach using Deeplex for rapid determination of drug resistance profiles of M. tuberculosis as part of the clinical trial Pragmatic Use of Next-generation Sequencing for Management of Drug-resistant Tuberculosis (TSELiOT).





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Christoffel J Opperman

​​Doctoral candidate​​

14487616@sun.ac.za

Project Description:​ ​The study aims to: 1) Describe NTMs that are clinically relevant using descriptive epidemiology, spatial mapping, and clinical analysis of cases diagnosed in the Western Cape - a retrospective study over six years. 2) Prospectively, characterize Mycobacterium species with WGS, Sanger sequencing, and proteomics (MALDI-TOF) that remained unidentified following the Mycobacterium CM/AS line probe assay (LPA) performed on clinical samples within the NHLS, Green Point complex, TB-laboratory, Cape Town. 3) Illustrate the antibiotic susceptibility profiles of clinically relevant NTM isolates in the Western Cape, collected prospectively, with the NTM-DR LPA, Sensititre Mycobacteriaplates, and proportional method (BACTEC MGIT 960 system).   ​​


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Sarishna Singh

​​Doctoral candidate​​

sarishna.singh@nhls.ac.za

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Project Description:​ Isoniazid-resistant (INH-R) tuberculosis in the Western Cape, a descriptive study of clinical characteristics and outcomes. We aim to describe the epidemiology of NH-R in patients living in the Western Cape Province with the objectives: 1) a retrospective description of the  NH-R in patients diagnosed over a five-year period (2017-2022);  2) Identify the percentage of patients within this cohort that gained additional resistance; 3) Prospectively determine the burden of NH-R; 4) Compare treatment outcomes in patients with NH-R to treatment outcomes in patients with drug-susceptible TB  in both periods; and  5) Determine the areas where NH-R is concentrated (hotspots).​


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Tuelo Mogashoa

​​Doctoral candidate​​

22385924@sun.ac.za

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Project Description:​ Tuelo’s project is based on using next-generation sequencing to characterize rifampicin-resistant M. tuberculosis strains circulating in Botswana. Her project will also evaluate transmission dynamics of rifampicin-resistant M. tuberculosis strains as well as evaluate treatment outcomes and factors associated with unsuccessful treatment outcomes among people diagnosed with rifampicin-resistant tuberculosis (RR-TB). Data from this project will provide insights into the molecular epidemiology of RR-TB in Botswana. She is interested in TB molecular epidemiology, drug resistance, and bioinformatics and is very passionate about capacity building.



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Zainab Kashim-Bello

​​Doctoral candidate​​

zainabkb@sun.ac.za

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Project Description:​ Comparison of different outbreaks of MDR-TB in Western Cape province targeting genetic polymorphisms, drug-resistance conferring and compensatory mutations using WGS Analysis of the genomes of MDR-TB strains in the Western Cape Province, South Africa over a 12-year period will provide information about the changes in strain diversity, the potential to identify new possible outbreaks, and with early intervention, i.e. rapid diagnostics, early personalized treatment regimens, and close monitoring of patients. The study will also provide information on which drug combinations could potentially be more effective in specific communities, since there will be comparison of outbreaks amongst different communities.


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Astrid Paulse

​​Masters candidate​​

paulseag@sun.ac.za

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Project Description:​ Resistance to the novel nitroimidazole drug class in M.tuberculosis –  Novel clinical variants within the six target genes of pretomanid (PMD) and delamanid (DLM) were investigated to determine whether low levels of resistance between the two drugs exists between DLM-naïve patients through a genomic approach on resistance-associated genes (fbiA, fbiB, fbiC, fbiD fgd1 and ddn) and in vitro generated mutants to see whether they resemble resistant clinical strains and may serve as a proxy to investigate cross-resistance.


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Charne Glanz

​​Masters candidate​​

cglanz@sun.ac.za

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Project Description:​ Nanopore sequencing of M. tuberculosis – a handheld solution to comprehensive drug susceptibility testing: The aims of this project are to adapt and optimize workflows to enable DNA extraction directly from either decontaminated sputum or primary MGIT cultures, to compare manual library prep and automated library prep for MinION sequencing, and to build a bioinformatics analysis pipeline for MinION sequencing data. This project will move TB diagnosis closer to the point of care, enabling a more rapid prescription of treatment regimens to patients and thereby minimizing the spread of TB disease and drug-resistance.


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Morwatshehla Paul Modjadji

​​Masters candidate​​

modjadji@sun.ac.za

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Project Description:​ Portable diagnostics of M. tuberculosis: The aim of the study is to evaluate targeted deep sequencing to detect drug-resistance causing mutations in Mycobacterium tuberculosis using portable instruments which will be achieved by setting-up targeted deep sequencing on MinION using either purified DNA or DNA extracts from early positive cultures. 



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Magdalene Pine Adjei

​​Masters​ candidate​​

magdalenepa@sun.ac.za

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Project Description:​ Method development for phenotypic isoniazid drug susceptibility testing in a high throughput setting. The aim of this study is to develop a phenotypic isoniazid drug susceptibility testing method that features ease of use, low cost and high accuracy to be used in practical clinical settings. 





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Labeeqah Harris

​​Masters candidate​​

lharris@sun.ac.za

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Project Description:​ Determining the role of an inhA genomic mutation in the cell wall of M. tuberculosis. The inhA promoter region contains genes involved in the synthesis of mycolic acid, which are an integral part of the M. tuberculosis cell wall. We are evaluating whether there is a difference in cell wall composition between M. tuberculosis wild type and an inhA promoter mutation by analyzing extracted mycolic acid, evaluating membrane fluidity and integrity; and comparing cell wall thickness using various microscopy techniques. This project will contribute to understanding the role of inhA promoter mutations as an additional compensatory mutation in drug-resistant isolates.