This PhD opportunity is being offered as part of the LSTM and Lancaster University Doctoral Training Partnership. Find out more about the studentships and how to apply.
| Abstract | Acute febrile illnesses account for 40% of child deaths in sub-Saharan Africa, and an unknown level of morbidity and mortality in adults. A large proportion of these infections are zoonoses, either transmitted directly from animals, or via arthropod vectors. However, diagnosis of zoonoses is not widely pursued in low resource settings. This contributes to low awareness of zoonoses which hinders early detection and effective clinical management of fever. The LSTM Diagnostics group is part of an NIHR Global Health Research Group, with collaborators from the UK, Ethiopia, Kenya and Uganda, including experts in paediatrics, epidemiology, microbiology, social science, diagnostics development, infectious diseases and zoonoses/arboviral research. The overall aim of this consortia is to improve the diagnosis and management of zoonotic causes of fever in children in sub-Saharan Africa. This PhD studentship will focus on the design and development of new diagnostic methods for detecting key zoonotic causes of fever, including brucellosis, Q fever, and Rift Valley Fever. Tests will be developed using a range of cutting-edge diagnostic technologies that are being utilised at LSTM, including isothermal molecular methods such as LAMP and CRISPR/Cas, and monoclonal antibody labelled graphene biosensors. Throughout this process the student will have the opportunity to collaborate with several industrial partners within the diagnostic sector, and work with various prototype platforms. Tests will be developed at LSTM, validated using cultured pathogens and existing sample banks with the BLS3 laboratories (full BSL3 training will be given), and finally evaluated at one or more of our partner sites in Eastern Africa using clinical samples. The Project will also involve next generation sequencing of key outbreak pathogens, to assess pathogen diversity and transmission, and assess the suitability of genomic diagnostic targets. This work will be done in-country using portable MinION sequencing. This exciting project, within the Department of Tropical Disease Biology has the potential to deliver new diagnostics for these priority One-Health pathogens, and provide tangible translational outputs. The supervisory team includes, laboratory, clinical and commercial experience ensuring all aspects of the project are well covered. |
| Where does this project lie in the translational pathway? | T1 - Basic Research,T2 - Human /Clinical Research |
| Methodological Aspects | Quantitative methodologies will be utilised in the diagnostic evaluation study design, and also in the analysis of evaluation data. Whilst standard diagnostic accuracy will be calculated, we will explore the use of latent class analysis and binomial mixed effect models to provide point-estimates for sensitivity. Bioinformatics will be used to identify optimum sites of conservation within pathogen genomes to target the molecular assays. The laboratory methods used will include Next generation sequencing, RT-qPCR, RNA/DNA extractions, cell culture, protein expression, and a variety of novel diagnostic methods including CRISPR/Cas and graphene biosensors. |
| Expected Outputs | This project will generate high quality publications in the field of zoonoses diagnostics, specifically on the design and evaluation of the diagnostic tests. This highly translational work will also aim to progress tests through the development pipeline to commercialisation, via the generation of IP. Previous and current PhD students in the group have all published one or several high-quality first-author papers, and recent work from the team has resulted in high-impact publications in journals including Nature Communications, Lancet Infectious Diseases and Microbial Genomics. This project aims to generate a sizeable impact on how fever is diagnosed in Eastern Africa, and the existing network of collaborators within the Global Health Research Group will allow for new tests to be rapidly evaluated within this setting to generate the data needed to support test implementation and policy change. We will encourage the student to use results obtained in this project as the foundation for early career fellowship applications from the Wellcome Trust and MRC and will assist with compiling these. |
| Training Opportunities | The student will receive training on a wide variety of laboratory techniques at LSTM, including mammalian cell culture, Biosafety level 3 laboratory work, qPCR/LAMP, DNA sequencing, and diagnostic test development. The Global Health Research Group includes a cohort of MSc / PhD students from the East African partner institutes, and the student on this project will have the ability to collaborate and co-develop research ideas with this existing network. Experience of working in LMIC laboratory settings will also be gained via our collaborations within Ethiopia, Kenya and Uganda, where the test evaluation will take place. Via working with our industrial partners the student will gain exposure to the commercialisation of research, and gain key skills in research translation. We will support the student in identifying and applying for external funding opportunities e.g. Bioinformatics courses |
| Skills Required | All necessary training will be provided |
| Subject Areas | One Health, Neglected Tropical Diseases |
| Key Publications associated with this project |
DOI: 10.1128/msphere.00027-25 https://dx.doi.org/10.2139/ssrn.5293260 doi: 10.1016/j.prevetmed.2024.106345. doi: 10.1186/s12879-024-09162-x |