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Research

Research

Our research teams are currently investigating some of the biggest and most compelling questions in modern science, with the aim of contributing to one or more of the following research goals, with a focus on sub-Saharan African populations.

  • Uncovering African genomic diversity
  • Delineating the molecular epidemiology and evolutionary biology of diseases
  • Understanding disease by studying the life-course of individuals
  • Discovering the molecular basis of host defence mechanisms
  • Exploring novel drug targets and dynamic responses to treatment

Our research projects past and ongoing include:

AWI-Gen (Africa Wits-INDEPTH partnership for Genomics studies)
  • The Africa Wits-INDEPTH partnership for Genomic Studies is the flagship project for the SBIMB. The study is a partnership between Wits University and the International Network for the Demographic Evaluation of Populations and their Health in low and middle income countries (INDEPTH). This NIH-funded Human Heredity and Health in Africa (H3Africa) study aims to examine genomic and environmental factors that influence body composition, body fat distribution and cardiometabolic disease risk in middle aged African populations. For more information visit https://h3africa.org/.

The project was investigated between 2012 and 2023. Sub-projects and project emanating from this study are:

Longitudinal study: HAALSI

SBIMB role: DNA extractions

Genetics and Population Structure: Risk Score Methods and Analysis for Populations of Diverse Ancestry (PRIMED)

CARDINAL project funded by the NIH (2021-2026) is a collaboration with the University of Maryland. This project brings together several cohorts of African ancestry to build a large cohort of over 50,000 participants with relevant phenotype and genomic data, referred to as the CARdiometabolic Disorders IN African-ancestry PopuLations (CARDINAL). The AWI-Gen study will contribute data of over 10,500 participants. Prof Michele Ramsay is the co-PI for this project.

Understanding the relationship between the gut microbiome, and cardiometabolic disease and aging in African populations:

Research is focused on profiling the gut microbiome of individuals in Soweto, Johannesburg, and in Agincourt (Mpumalanga). The study aimed to characterise the microbiome composition and community structure in these cohorts; and to explore the association between cardiometabolic disease risk factors and metagenomic profiles.

Aging, body fat distribution and cardiometabolic disease risk factors in menopausal African women:

The aim of this study is to examine how menopause contributes to weight change, diabetes and CMD risk in midlife women in the AWI-Gen cohort.

VariantBio

The SBIMB is collaborating with Variant Bio (A venture capital company based in the USA) to develop and eQTL dataset for blood in black South Africans. This project leverages knowledge generated by AWI-Gen, through the analysis of genomic data to identify individuals according to specific criteria for inclusion. The project aims to understand the effects of genetic variation on gene regulation in South Africa individuals in three South African AWI-Gen study sites.  Sample analyses and data generation are complete and currently scientists are working on data QC and analyses.

AWI-Gen-XHALE: Establishing a network to explore respiratory disease in the context of multi-morbidity in four African countries:

This research aimed to build a network of expertise to measure respiratory health in the participants of an established African multicohort, AWI-Gen, that focused on cardiometabolic diseases. This network focused on respiratory health within the context of multimorbidity and include collaborators from countries within Africa and abroad to develop a platform to study respiratory disease in different African contexts, with a particular focus on how this co-occurs with cardiometabolic disease. This project developed capacity by including training on methods to measure, interpret and research respiratory health at the six different African study sites in Kenya, Burkina Faso, Ghana, and South Africa. Currently data from this study is being mined to produce publications on African genomic data which is underrepresented.

LEAP-EPI

Air pollution is a leading cause of premature mortality, and acute and chronic health effects globally. Sub-Saharan Africa faces a growing burden of air pollution driven by human activities and climate change, but whether outcomes from studies in Europe and North America can be extrapolated to African populations is poorly understood. Sufficiently granular environmental data on air pollution exposure is lacking from longitudinal cohorts in sub-Saharan Africa. The AWI-Gen-XHALE Academy of Medical Sciences GCRF research network identified air pollution data linkage as a key need and opportunity. While many exposure studies have been conducted in Africa, the AWI-Gen consortium offers unprecedented longitudinal health, phenotype, and exposure (indoor cooking and smoking) records, plus genetic data, which can be related to air pollution exposures.

This project aims to; (1) perform a comprehensive assessment of available global and local air pollution data across two (urban and rural) AWI-Gen XHALE study sites; (2) Develop a sustainable sampling methodology for indoor and outdoor air quality data at different levels of exposure in low- and middle-income contexts; (3) to build local capacity for air quality research-involve local communities in developing sensor deployment and exposure mitigation strategies; and contribute evidence for national policies.


Figure 1: AWI-Gen research project sites.
Multimorbidity in Africa: Digital innovation, visualization, and application (MADIVA)

This is a population cross-sectional study and it includes all significant infectious and non-communicable diseases that add to the burden of multi-morbidity. The problem of multiple co-occurring diseases significantly adding to the health burden in Africa. The MADIVA Research Hub is using existing data sets or data sets that have been or are routinely being collected by other projects. No recruitment of study participants is involved in this project. Currently, the study is focused on developing and applying data science techniques to link the different data sets, build dashboards for different stakeholders and to apply new machine learning techniques to automatically stratify populations for risk profiles to different diseases, including the use of polygenic risk scores.

H3ABioNet

The SBIMB hosts the Wits node of the NIH-funded pan-African bioinformatics network comprising 32 bioinformatics research groups across 15 African countries. H3ABioNet fosters the development of bioinformatics capacity on the African continent to support H3Africa and other African researchers.

For more information visit https://h3abionet.org/ Subaward – Prof Scott.

eLwazi Open Science Data Platform for Africa

SBIMB researchers work in collaboration with Computational Biology (CBIO) division at the University of Cape Town. eLwazi, symbolizing “knowledge”, will be a modular, scalable platform based on the Data Biosphere concept, that enables the application of data science tools to drive novel discoveries for health.

More details of this project at the link: https://reporter.nih.gov/search/zrfhGFB-aEKROaCdWN0Qrw/project-details/10311569

Cancer Genetics

Cancer Genetics studies aim to discover genetic variants which are driving the development of common African cancers such as breast, cervical, colorectal, oesophageal and prostate cancer in African populations, and to identify mutational signatures which may provide clues to environmental mutagens involved in oesophageal cancer.

  • ERICA-SA
    • Evolving Risk Factors for Cancers in African Populations: Lifestyle, Infection, Genetic Susceptibility and cancer in South Africa: development of research capacity and an evidence base for cancer control” a collaborative research Project lead by the SAMRC’s Burden of Disease Research Unit, National Cancer Registry and SBIMB via Prof Chris Mathew was funded by the South African Medical Research Council and the UK Government’s Newton Fund through the UK Medical Research Council. The type of cancers studied under this project were: breast cancer, oesophageal cancer, cervical cancer and infection-related cancers such as Kaposi Sarcoma.
  • Oesophageal cancer
    • The Genomic Analysis of African Oesophageal Squamous Cell Carcinoma project was a collaborative between Prof Iqbal Parker from UCT with Prof Chris Mathew at the SBIMB. The project was funded by the UK Newton fund, GSK and SA MRC.

The project titled; “Identifying genetic markers of susceptibility to African oesophageal cancer” aimed to find out whether variation in the genetic code of human genomes contributes to the high incidence of oesophageal squamous cell cancer (OSCC) in the Black populations of sub-Saharan Africa, and particularly in South Africa. Large studies have been carried out in other parts of the world with a high incidence of this form of cancer, especially in China. This has led to the discovery of genetic variants (i.e. changes in the genetic code) in some genes which increase the risk of OSCC, so our first aim is to test these genes and variants in our local African populations to see whether they also increase risk of OSCC here. The reason for wanting to find such genes and variants is two-fold. One is that the identity of the genes would give us a window into the molecular pathways that underlie the development of these cancers, and this knowledge may help us to develop new and better treatments for this cancer, which currently has a dismal prognosis. The second reason is that if we can identify genetic profiles that confer a high risk of OSCC, we could investigate the potential use of these profiles in screening middle-age African people for OSCC before they show symptoms of this cancer. This could result in a large improvement in survival and cure rates for this form of cancer. This project was funded by the Cancer Association of South Africa (CANSA).

  • Breast Cancer
  • Colorectal
  • Cervical
Pharmacogenomics in African populations

Pharmacogenomics in African populations studies aim to understand the genomic diversity of African populations important in drug response. The research spans the whole value chain from discovery genomics, biochemical evaluation to clinical studies. The aim of these studies is to deliver precision medicine for improved treatment outcomes with respect to drug safety and efficacy.

  • GSK ADME
    • The ADME genes play an important role in the absorption, distribution, metabolism and excretion of pharmaceutical drugs. This GSK-funded study aimed to identify functional ADME variants from whole genome sequences (WGSs) in African populations. The project was conducted between 2018 and 2022.
  • Tamoxifen cancer study
    • Research aims to understand the role of a black African specific low activity variant of the CYP2D6 gene, CYP2D6*17, on the efficacy of tamoxifen in breast cancer treatment. Biochemical characterisation of the variant will involve use of an iPSC-derived hepatocyte-like cell model. Clinical evaluation will involve pharmacogenetic and pharmacokinetic studies in breast cancer patients.
  • ATDili (Anti-Tuberculosis Drug induced Liver injury)
    • This projects focus is to combine pharmacogenomic sequence data on ADME genes with clinical and pharmacokinetic data on ATDILI patients of African ancestry receiving anti-TB treatment to explore drug-gene interactions, understand TB treatment adverse events and guide biomarker development.
  • AGORA
    • This project is looking into increasing the knowledge about genetic variability in Africa in the genes that contribute to antimalarial and anti-Tuberculosis (TB) drug processing. The project addresses the gaps of knowledge about the functional impact of genetic variability at the molecular level. The research is focused on adopting integrative methods throughout the various stages as the project involves, (1) heterogenous data sets from research collaborators and public datasets and, (2) different approaches for analysing the data. The project has access to rich and extensive genomic data from thousands of ethnically diverse Sub-Saharan African individuals. Data analysis of this project includes the use of genomic investigation approaches, biomedical literature text mining, molecular modelling, and biomolecular simulation. The outcome knowledge provided by the analysis stages of this project will serve in populating public data repositories developed by African researchers.
  • Hypertension study
    • PGx study: Title: Exploratory framework for a pharmacogenetics guided treatment algorithm for high blood pressure in black South Africans.
      • High blood pressure (BP) is a risk factor for stroke, cardiac failure, coronary artery disease and chronic kidney disease. Hypertension (HT) is common among black South Africans and can be difficult to treat effectively. This study aims to develop an evidence-based pharmacogenomics (PGx) guided algorithm to assist clinical decision making for the treatment of HT among black South Africans to mitigate the risk for progression to cardiovascular disease (CVD) later in life.
    • Ophthalmological Genetics
    • COVIGen-SA
    • Depression Genetics in Africa (DepGenAfrica)
      • In the last decade, huge advances in depression genetics have been observed in European and East Asian populations only. This project will focus on developing a better understanding of depression genetics in African populations to correct this inequity. The latest advanced statistical genetics methods to find genetic risk factors for depression that are specific to African populations and that are shared across populations will be applied. The vision is to establish the methods, networks, expertise and knowledge-base necessary for rapid acceleration of depression research worldwide. To do so, research will focus on the most understudied continent whose populations have the greatest genetic diversity. The aim is to characterise depressive syndromes and identify the genetic architecture of major depressive disorder (MDD) in 10K individuals living in Western and East sub-Saharan Africa through new data collections and collaborations with other projects.
Successful Funding The SBIMB senior scientists actively apply for grants throughout the year. Our senior scientists and postgraduate students have collectively raised research grants that have sustained the SBIMB over the past five years, however more funding is needed to ensure our sustainability into the future. Our students are encouraged to actively seek for funding as part of their training. Our funders are both national and international funding bodies.
Funders The SBIMB project management team together with support from Wits Foundation, are directing fundraising efforts towards a variety of international, national, public and private sources. Potential funders can contact us directly to obtain more details on the SBIMB initiative, the costs required to establish this world class biomedical research facility and how they can contribute to its sustainability. Funders are encouraged to participate in a modular funding strategy.
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