Recent studies in Africa and India (countries with high TB- and HIV-burdens) reported increased frequency of zoonotic tuberculosis (zTB) in humans caused by other members of the Mycobacterium tuberculosis complex (MTBC) like M. orygis, indicating that M. bovis infection may be an inadequate proxy for zTB. Similarly, nontuberculous mycobacteria (NTM) lung disease in people is more frequently reported in Africa because of environmental NTM like M. avium complex. NTM are naturally resistant to various drugs commonly used to treat MTBC infection and are often indistinguishable from MTBC when conventional MTBC “specific” immunological tests are used in humans and animals. Consequently, the management and treatment of infected patients are substantially different and complicated by the absence of appropriate culture-independent tests for the combined detection and differentiation of MTBC and NTM. We hypothesize that zoonotic pathogens like M. orygis and M. avium complex are more abundant in livestock, their environments and nearby wildlife than previously thought, especially in areas with immunocompromised people, leading to potentially high transmission risk interfaces. The goal is to develop culture-independent detection and genotyping tests to enhance zoonotic Mycobacteria spp. detection and differentiation directly from livestock specimens collected from low-resource areas, their environment and near-by wildlife reservoirs. Zoonotic tuberculosis (zTB) in people is now suspected to be more frequently caused by members of the Mycobacterium tuberculosis complex (MTBC) other than M. bovis. Similarly, environmental non-tuberculous mycobacteria (NTM) like M. avium complex, also appear to be more frequently infecting people in developing countries with a high TB/HIV burden, causing NTM lung disease. The gold-standard diagnostic test for TB is mycobacterial culture and cannot distinguish between MTBC and NTM and it requires long incubation periods. Therefore, I aim to develop rapid culture-independent tests for improved detection directly from specimens collected from livestock from low-resource areas, their environments and neighbouring wildlife. The impact of the study will include: 1) enhanced capacity for improved surveillance, 2) identification of sites where human infection risk is significant to improve detection and interventions, 3) find area where risk of emergence of novel pathogenic Mycobacteria strains is high, and 4) increased awareness.

The proposed project seeks to respond to the challenge of cardiovascular disease (CVD) which is a growing public health concern in South Africa. The risk of CVD is heightened in marginalized urban communities where inadequate access to nutritious food, financial constraints and cultural food preferences often result in unhealthy diets. Scientists exploring the biomedical nature of CVD could benefit from knowing more about the lived realities underlying problematic food choices. Using a series of participatory approaches and visual outputs, SLF will bring together residents of a poor township in the outskirts of Cape Town and a CVD research team at Stellenbosch University. The project aims to enable all participants to share their perspectives about what it means to eat well, engage in dialogue about the implications of diet on health, and discuss the aims of CVD research. This knowledge exchange process will be fostered through a series of interactive workshops and the creation of photodiaries, digital stories and a collaborative video. These visual outputs will be used as communication tools which will be widely disseminated to show the complex and interconnecting factors that influence food choices, health, and the approach to biomedical research that responds to dietary intake.

Infectious diseases pose a grave threat to humanity due to factors such as increased travel, deforestation, and population growth. To address this challenge, Global.health aims to enhance the response to infectious diseases by creating an integrated platform that provides real-time access to clinical, epidemiological, genomic, and contextual data. This platform will train predictive models to effectively respond to current and future disease threats and promote equitable partnerships to improve data sharing and strengthen data science capacity in low- and middle-income countries. The project has four main goals: 1) developing rapid data dissemination pipelines and integrating them with the World Health Organization (WHO) for early international coordination and response; 2) building data integration pipelines and predictive models for climate-driven disease outbreaks in vulnerable regions; 3) developing tools to detect and correct biases in infectious disease data, improve data quality, and enable privacy-preserving distributed analytics; and 4) increasing adoption of Global.health's technology stack by engaging with WHO teams, regional offices, member states, partner organizations, and the research community. By achieving these aims, Global.health will significantly enhance the infectious disease data ecosystem, assess the value of integrating different data types during outbreaks, and create adaptable open-source tools applicable beyond infectious diseases.

Membrane proteins provide a multitude of functions essential to the life of the cell, and yet extracting them in an active form remains exceptionally challenging. In recent times an amphiphilic polymer, poly(styrene-co-maleic acid) (SMA) has gained significant traction as an effective agent for extracting and stabilising membrane proteins in phospholipid nanodiscs. Unlike conventional methods based on detergents, the method also extracts the lipids surrounding the protein, helping to preserve native activity. Although the original SMA polymer provided a good solution for demonstrating the utility of this approach it is becoming increasingly clear that further development of the polymer is required to fully capitalise on the unique aspects of the method. This project aims to address this by providing a technical resource for the community for generating improved, bespoke polymers matched to end users need allowing them to: 1) Tune the lipid environment within the nano-particle to optimise protein activity by introducing a variety of comonomers, including aromatic, linear aliphatic and branched aliphatic into the established maleic anhydride copolymer 2) Harness functionalised "plug-n-play polymers" that allow researchers to easily modify the polymers for downstream applications These polymers will be tested by the community and delivered through an integrated commercial supply chain. Membrane proteins (MPs) form about 70% of all drug targets, but they are very difficult to isolate in their intact, stable and fully functional form. Since about a decade, three commercially available polymers have been used to transform cell membranes into nanodiscs and it was discovered that these nanodiscs offer interesting possibilities for the isolation of MPs. Although the three commercial polymers work reasonably well, they were never developed specifically for this application and there are several shortcomings that still need to be overcome. In this project, we aim to develop the next generation of amphiphilic copolymers, dedicated for the isolation of MPs. In collaboration with several scientists from the MP field we will enhance the efficiency of the amphiphilic copolymers and also introduce additional functionality that is needed to expand the utilisation of the isolated MPs in the field of drug discovery and beyond.

In South Africa, state-funded social protection for disabled children has primarily been through the Care Dependency Grant (CDG). The CDG is distributed to the caregivers of these children and provides important financial assistance, but it is under-researched. Little is known about caregivers’ access and utilisation of the CDG, what the value of complementary interventions might be, how doctors assess need and deservingness, and how government agencies conceive of and communicate about the CDG. The proposed study will investigate these and other questions in a qualitative study using ethnographic and participatory methods, with a specific focus on the Cape Winelands district. Participants will include caregivers of children with disabilities, assessing doctors, South African Social Services Agency (SASSA) staff members, and organisations working with disabled children. Findings will be discussed with reference to broader debates around social protection, development, poverty alleviation, and access to health and education for disabled children. A better understanding of how this grant is conceived of, used, and distributed from the perspective of different stakeholders will build knowledge in this underdeveloped area. It will also produce important initial evidence for potential future interventions to improve the social protection of disabled children and their caregivers in South Africa. Following a medical assessment process, the Care Dependency Grant (CDG) is distributed by the South African government to caregivers of children with disabilities. We do not know much about how families access or use this money, and whether this is the most useful kind of government assistance. There are also minimal narratives available from associated civil society organisations, government agencies who implement this grant, and doctors who assess eligibility. This study will focus on rural communities in a specific part of the Western Cape province. I will use participant observation and interviews to speak with the various stakeholders involved and find out more about their understanding of the CDG. This work will also lay groundwork for future research to help the government improve communication to reach eligible caregivers, broaden the kinds of support they provide, and if need be, reconsider the CDG assessment process.