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 | TB continues being the leading infectious killer worldwide with more than 5 million of new TB cases reported every year and causing 15 million of deaths over the past decade. TB takes the life of approximately 1.3 million of people every year of which 12% are people leaving with HIV (PLHIV) and 16% are children. TB is curable disease with high rates of treatment success for those who are promptly diagnosed and treated. However, a large part of people with TB who are not correctly diagnosed. Current diagnostic testing for TB is based on sputum-based diagnostics (PCR and/or culture and/or smear microscopy). Sputum production is however scarce or absent in some patients for example in children and people leaving with HIV and the diagnosis of TB infection among these patients is a daily challenge for clinicians. There is only a commercially available test for diagnosis of TB in urine which detects Lipoarabinomannan (LAM) in urine but its sensitivity is very limited and only recommended to use among PLHIV with low CD4 counts. In this project, the successful applicant will use a variety of immunological and molecular approaches to identify novel urinary biomarkers associated with active TB with a particular interest in patients co-infected with HIV and in children as are the populations where the availably of a sputum-free tests will be of more value. We will use urine from TB patients to explore excreted biomarkers of pathogen origin and host origin due to immunological response and tissue damage during TB disease. The most promising biomarker(s) will be used to develop test prototypes. Following test development, validation experiments will be performed using human urine samples from TB patients. The outcomes of this project will be used to support the progress towards the much-needed development of sputum-free diagnostics for TB. The supervisory team, across both the Department of Clinical Sciences and Tropical Disease Biology, includes members with laboratory and clinical experience and the candidate will have the opportunity to travel to endemic countries and work closely with our long-term collaborators in this exiting project. |
| Where does this project lie in the translational pathway? | T1 - Basic Research |
| Expected Outputs | The expected outputs for this project will be high-impact papers due to the importance of this disease and novelty of the programme, new biomarkers and new tools that could be readily impactful and will have the potential to lead to further progress through the development pipeline for commercialisation. Pilot data will be used to encourage the candidate to apply for fellowship applications to encourage career development. |
| Training Opportunities | The student will be exposed to a wide variety of research training opportunities including: -Molecular techniques, including PCR, sequencing, -Immunological approaches, including ELISA, western blot, lateral flow technology -Training in scientific writing and presenting -Experience of working in laboratory settings in endemic countries will also be gained via our collaborations in TB endemic countries -We will support the student in identifying and applying for external funding opportunities for training and future grant applications and fellowships. |
| Skils Required | An ideal candidate should have a strong molecular biology background and/or proteomics and/or computational skills, but training will be provided as necessary. We expect the student to possess strong organisational and project-solving aptitudes with good inter-personal skills. |
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Key Publications associated with this project |
Cubas-Atienzar, A.I., Williams, C.T., Karkey, A., Dongol, S., Sulochana, M., Rajendra, S., Hobbs, G., Evans, K., Musicha, P., Feasey, N. and Cuevas, L.E., 2021. A novel air-dried multiplex high-resolution melt assay for the detection of extended-spectrum β-lactamase and carbapenemase genes. Journal of Global Antimicrobial Resistance, 27, pp.123-131. |
| Byrne, R.L., Aljayyoussi, G., Greenland-Bews, C., Kontogianni, K., Wooding, D., Williams, C.T., LSTM Diagnostics group, Falcon Steering group, de Vos, M., Body, R and Cubas-Atienzar, A.I., 2023. Comparison of the analytical and clinical sensitivity of thirty-four rapid antigen tests with the most prevalent SARS-CoV-2 variants of concern during the COVID-19 pandemic in the UK. medRxiv, pp.2023-07. | |
| Cuevas, L.E., Santos, V.S., Lima, S.V.M.A., Kontogianni, K., Bimba, J.S., Iem, V., Dominguez, J., Adams, E., Atienzar, A.C., Edwards, T. and Squire, S.B., 2021. Systematic review of pooling sputum as an efficient method for Xpert MTB/RIF tuberculosis testing during the COVID-19 pandemic. Emerging infectious diseases, 27(3), p.719. | |
| Byrne, R.L., Wingfield, T., Adams, E.R., Banu, S., Bimba, J.S., Codlin, A., Atienzar, A.C., Garg, T., John, S., Gurgel, R.Q. and Sander, M., 2024. Finding the missed millions: innovations to bring tuberculosis diagnosis closer to key populations. BMC Global and Public Health, 2(1), p.33. | |
| Schiff, H.F., Walker, N.F., Ugarte-Gil, C., Tebruegge, M., Manousopoulou, A., Garbis, S.D., Mansour, S., Wong, P.H.M., Rockett, G., Piazza, P. and Niranjan, M., 2024. Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers. JCI insight, 9(8). |