Grand Challenges is a family of initiatives fostering innovation to solve key global health and development problems. Each initiative is an experiment in the use of challenges to focus innovation on making an impact. Individual challenges address some of the same problems, but from differing perspectives.
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Fidele Ntie-Kang, a computational chemist at the Department of Chemistry, University of Buea in Cameroon, will establish a state-of-the-art drug discovery regional center for Central Africa that utilizes natural products from across the continent to identify new antiviral drugs suitable for resource-limited regions. Dr. Ntie-Kang is a pioneer in harnessing the diverse African flora for drug discovery purposes. His research group is building an online natural products database, which contains compounds isolated from plants, fungi, corals and bacterial species growing in Africa. He will set up a unique team of synthetic organic chemists, natural product chemists, computational chemists, microbiologists, biochemists and artificial intelligence experts, and build an open access pan-African library of naturally occurring compounds and a cloud-based computing platform. The team will combine virtual and in vitro screening techniques to identify natural compounds targeting the SARS-CoV-2 spike protein and the HIV Vpu protein, as well as promoting HIV latency-reversal. They will also train students to expand research capacity, and transfer the knowledge and technology developed during the project to other research institutes.
Annettee Nakimuli, Associate Professor of Obstetrics and Gynaecology and Dean of the School of Medicine at Makerere University in Uganda, will identify predictors of adverse pregnancy outcomes in Ugandan women with a focus on Great Obstetrical Syndromes (GOS), such as pre-eclampsia, to help develop context-relevant interventions for prevention and treatment. Dr. Nakimuli is an internationally-recognized research leader in maternal health for Africa. She performed the first genetic case-control study on pre-eclampsia among indigenous Africans, and identified different biological factors to those found in European studies, which helps explain the higher incidence. Building on her experience setting up cohort studies, she will prospectively collect biological samples and clinical data from a large cohort of 4,000 women throughout their pregnancies at Kawempe and Mulago Hospitals in Kampala to identify predictive biomarkers, and establish a biobank and database to facilitate future research. She will also implement artificial intelligence for data analysis to identify relevant socio-epidemiological, clinical, and biological features that contribute to the development of Great Obstetrical Syndromes.
Yaw Bediako, Founder and Chief Executive Officer of Yemaachi Biotech and researcher at the West African Centre for Cell Biology and Infectious Pathogens in Ghana, will bring together African biotech and academia with the Francis Crick Institute to provide important insights into how vaccines can be designed to work more optimally among African people. The African continent has the highest infectious disease burden in the world but almost no capacity for vaccine development or testing. Instead, most vaccines are tested in healthy Caucasian adults in high income countries, and many have lower efficacy among African populations. Dr. Bediako studies immune function in African populations and is devoted to building research capacity in Africa. He developed and successfully deployed the first national SARS-CoV-2 variant tracker on the continent, which displayed the distribution of viral variants in real-time. He will perform a prospective cohort study, and use molecular, cellular, and data-analysis approaches to investigate if the cellular and humoral immune responses to the AstraZeneca COVID-19 vaccine differ between Ghanaian and UK populations, and identify the effect of host genetic diversity on vaccine response. These data will support more rational vaccine design among African populations.
Abdoulaye Djimde, President of the Pathogens genomic Diversity Network Africa (PDNA), will work to better prepare Africa to fight infectious diseases and tackle those of the future. Dr. Djimde’s research group uses molecular and genetic approaches to study malaria, and their results have supported policy decision-making in Mali and the West Africa sub-region. His work on anti-malarial resistance led to a change in first-line therapy, and his group also serves as a training ground for many scientists in Africa. Recognizing the importance of collaborative research across the continent for studying infectious diseases, he established PDNA, which is an African-led research network spanning sixteen countries. PDNA investigates the genetic diversity of human pathogens to inform disease control and elimination strategies. He will set up a PDNA Pathogens Genomics Institute in Mali equipped with genetic and molecular epidemiology infrastructure. The Institute will train the next generation of scientists, and study the emergence and spread of malaria, SARS-CoV-2, and anti-microbial resistance, and identify novel pathogens. They will also focus on engagement with communities and health policy makers across the member countries to support public health on the continent.
Isabella Oyier, Associate Professor and Head of Bioscience at the KEMRI-Wellcome Trust Research Programme in Kenya, will establish a national malaria molecular surveillance platform that is integrated into the Division of National Malaria Programme (DNMP) to directly translate research into policy. The malaria burden in Africa is no longer declining due to the emergence of new variants that are undetectable by standard diagnostics and resistant to the frontline antimalarial drug. Dr. Oyier, a leader in malaria molecular epidemiology, is committed to eradicating malaria in Africa. She pursues a collaborative approach by sharing resources across laboratories and partnering with key stakeholders to ensure research impacts policy. This approach enabled her to make critical contributions to the genomics surveillance and testing efforts during the COVID-19 pandemic in Kenya. She will establish a national data repository and a working group to develop a sustainable next-generation sequencing platform that can be easily implemented across malaria-endemic regions where sentinel health facilities will be established to collect samples. She will also build user-friendly bioinformatics pipelines to examine parasite genetic diversity and the distribution of resistance markers, and to present actionable data for policy decision-making.
Mainga Hamaluba, Head of Clinical Research at the KEMRI-Wellcome Trust Research Programme in Kenya, will develop a pragmatic adaptive trial platform to evaluate key interventions for improving child survival in East Africa in real-life routine practice conditions as a faster and lower-cost alternative to traditional randomized controlled trials. Dr. Hamaluba has led a wide-range of complex clinical trials, including oversight of a complement of COVID-19 prevention and vaccine trials. She will use newborn care and hypoxic-ischaemic encephalopathy (HIE; also known as birth asphyxia) as a case study for the platform. HIE is the leading cause of admission in a network of Newborn Units in Kenya and causes severe neurological disabilities in survivors. Leveraging an existing and unique clinical surveillance framework and biobank at her institute, she will conduct a pragmatic platform adaptive randomized controlled trial of three licensed treatments to evaluate their effect on newborn survival. She will also establish procedures to increase the speed, rigor, and adaptability of regulatory approval protocols for clinical trials, and focus on training and mentorship of local healthcare workers in clinical research.
Iruka Okeke, Professor of Pharmaceutical Microbiology at the College of Medicine, University of Ibadan in Nigeria, will develop sequence-based methods and leverage genomics data to jumpstart the development of diagnostics and vaccines for neglected bacterial pathogens in African settings. Professor Okeke has devoted her career to studying neglected enteric bacteria that can cause potentially fatal bloodstream and diarrheal infections. She recognizes the power of genomics approaches to improve surveillance and better define pathogen virulence. She has been developing lower-cost and simpler methods to traditional culture-based techniques for detecting difficult-to-culture bacterial pathogens directly from blood samples in minimally-equipped laboratories. These methods incorporate nanopore sequencing together with target enrichment by the CRISPR-Cas9 system for rapid, direct-from-specimen diagnosis and genomic surveillance. She will adapt these methods for identifying a range of pathogens directly from stool, urine, and other clinical samples. She will also grow a community of experts to support this project by training African scientists in molecular science and bioinformatics.
Collen Masimirembwa, Professor and founding President and Chief Scientific Officer of the African Institute of Biomedical Science and Technology (AiBST), Zimbabwe, will generate a research and innovation ecosystem, including training scientists and establishing centers of excellence in genomic medicine research, for the sustainable development of genomic and pharmaceutical medicine capability in Africa. Dr. Masimirembwa is on a mission to achieve world-class drug discovery and development capability in Africa. In 2002, he founded AiBST in Zimbabwe, and over the last ten years has organized a series of drug discovery and development courses across the continent to introduce the subjects and contextualize them for Africa. He will establish three centers of excellence in Zimbabwe, Kenya, and Nigeria to help launch an R&D biotechnology industry in Africa by forging partnerships with relevant stakeholders and training industry-focused scientists. He will also perform a prospective, multi-center clinical trial across several countries to determine the effectiveness of pharmacogenetic testing in reducing the incidence of adverse drug reactions and increasing treatment efficacy in African populations.
Jo-Ann Passmore, Associate Professor of the University of Cape Town in South Africa, will pilot the formation of the vaginal microbiome research consortium in Africa (VMRC4Africa) by establishing a network of researchers and centers of excellence for conducting research and clinical trials to promote women’s health across the continent. Dr. Passmore uses immune biomarkers and microbial-based approaches to study HIV and HPV pathogenesis and prevention in African women. Her work identified genital tract inflammation as a major predictor of HIV risk and pathogenesis, and revealed that inflammation reduces the efficacy of the anti-retroviral drug tenofovir, which is used to treat HIV. Her laboratory is a South African center of excellence in HIV prevention and she is committed to nurture and mentor young African researchers. She will establish the necessary infrastructure for African researchers to document the changing composition of the vaginal microbiota, beginning with South African and Kenyan women. They will use sequencing and build a biorepository to help identify health-promoting <em>Lactobacillus</em>-dominated microbiota in different geographic regions. These could be co-formulated into live biotherapeutic products to treat genital tract inflammation for women globally.
Nicki Tiffin, Professor at the University of the Western Cape, South Africa, will build an online platform – the African Data and Biospecimen Exchange – to facilitate equitable, ethical, and transparent data and biospecimen sharing on the continent, and promote research collaborations to improve health. Sharing biospecimens and data such as human genomics and pathogen sequencing data for use by other scientists is critical to sustain research in Africa. However current barriers that preclude sharing include high costs, the need for specialized formatting, and legal limitations for sensitive data. Dr. Tiffin has worked extensively across multiple health research domains, built research networks and collaborators across Africa, and is passionate about the effective use of health data in scientific research. She will build a platform for uploading standardized resource meta-data to reduce overhead costs, and provide practical guidance and online templates for sharing sensitive datasets. She will undertake a consultative process with domain experts to produce the design and functionality of the platform.