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 remains the leading infectious killer worldwide, responsible for 15 million deaths over the past decade and more than 5 million new TB cases reported every year. TB takes the life of approximately 1.3 million people every year, of which 12% are people living with HIV (PLHIV) and 16% are children. TB is a curable disease with high rates of treatment success for those who are promptly diagnosed and treated. However, a large part of people with TB are missed. 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 PLHIV. PLHIV often develop non-pulmonary TB, disseminated TB, and have difficulty producing sputum. TB diagnosis among these key populations is a daily challenge for clinicians. Currently, there is only one non-sputum-based diagnosis test for TB recommended by the WHO, which is based on the detection of Mycobacterium tb enveloped glycoprotein lipoarabinomannan (LAM) in urine. The current sensitivity of LAM testing is very limited and is only recommended for use among PLHIV with low CD4 cell counts. In this project, the PhD student will use a variety of immunological, molecular, and chemical approaches to identify novel urinary biomarkers associated with active TB, with a particular interest in patients co-infected with HIV and in children, as these are the populations where the availability of sputum-free diagnostics will be of greatest value. We will use urine from TB patients from Nigeria from different cohorts to explore excreted biomarkers, either of pathogen or host origin, derived from immunological response and tissue damage during active TB infection. The most promising biomarker(s) will be used to develop novel diagnostics in collaboration with industry partners. 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 diagnostic tests for the detection of the current TB missed cases among key vulnerable populations. |
| Where does this project lie in the translational pathway? | T1 - Basic Research,T2 - Human /Clinical Research |
| Methodological Aspects | This project applies a multidisciplinary methodological framework combining laboratory techniques for the discovery of novel biomarkers (mRNA, microRNA, mass-spectrometry) and for diagnostic development using the discovered biomarkers to develop novel tests (ELISA, Multiplex bead-based assays, PCR, etc) together with computational methods for data analysis and modelling. This project has a significant quantitative aspect as it will use bioinformatics to analyse sequencing and proteomic results and perform computational modelling combining the mRNA, microRNA, mass-spectrometry data with patient’s clinical metadata (eg. TB positivity, HIV positivity) and patients screening results (Xray, symptoms, CRP etc) to build diagnostic algorithms on the discovered biomarkers that better classify patients TB and HIV status. Gene expression data will also be integrated into the genome-scale human metabolic models to construct context-specific metabolic networks to investigate the metabolic pathways behind TB disease in key populations. |
| Expected Outputs | The expected outputs for this project will be high-impact papers due to the importance of this disease and the 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. We anticipate at least two first-author research papers from the student: a comprehensive analysis of urinary pathogen- and host-derived biomarkers in TB and a study linking transcriptome and proteomic data on the metabolic pathways responsible for TB disease among patients with and without HIV. Additional co-authorships are likely through collaborative studies with partner laboratories. Additional outputs will include abstracts and oral/poster presentations at leading national and international meetings (e.g., Union World Conference on Lung Health, ECCMID, BSI), with targeted engagement at translational fora focused on TB diagnostics and biomarker development. These outputs will position LSTM as a reference site for biomarker discovery and translational diagnostic development in TB. This work will directly underpin future grant applications and fellowships, and the student will be supported by the supervisory team to apply for these as a follow-up strategy upon completion of the PhD. The student will emerge with a strong quantitative and translational skillset, evidenced by publications and follow-up funding. In terms of impact, the project will generate biomarker signatures to guide development of non-sputum diagnostics, provide validated assays for triaging candidate biomarkers, and inform design of tests suitable for use in children and people living with HIV. Where appropriate, assay innovations or biomarker panels will be assessed with LSTM’s technology transfer office for intellectual property protection and partnering with industry and public-health stakeholders. |
| Training Opportunities | The studentship will provide comprehensive, interdisciplinary training designed to equip the candidate with both technical and professional skills. Core scientific training will include advanced molecular biology techniques such as mRNA sequencing and microRNA profiling, alongside chemical and analytical approaches, including mass spectrometry. Complementary expertise will be developed in omics bioinformatics, statistical analysis, and quantitative modelling, providing a rigorous foundation for biomarker discovery and validation. Professional development will encompass structured training in scientific writing, presentation, and dissemination, as well as mentorship in securing external training awards, fellowships, and future grant funding. The student will also benefit from international experience through laboratory placements in TB-endemic countries, thereby gaining first-hand exposure to the challenges of conducting research in global health settings. Finally, an internship with an industry partner will provide practical insight into biomarker discovery sciences to diagnostic development pipelines to maximise the translational skills, ensuring the student is well prepared for a brilliant future career. The studentship will provide structured professional development alongside scientific training. This will include workshops on scientific writing and presentation skills, tailored support for abstract and manuscript preparation, and mentoring in grant applications. The student will also have opportunities to present their work at leading national and international conferences, strengthening their communication and networking skills. Overall, the training programme is designed to develop a well-rounded researcher with advanced technical expertise, strong quantitative skills, and the ability to work effectively across academic, clinical, and industrial settings. This aligns closely with the MRC’s priority to train future leaders with the interdisciplinary and translational capacity needed to address major global health challenges such as TB diagnostics |
| Skills Required | We’re looking for a motivated individual with a grounding in computational skills, specifically analysing high volumes of sequencing data. Experience in building gene networks for metabolic analysis will be an advantage. Experience in wet testing laboratory techniques such as RNA extraction, RNA sequencing, PCR, ELISA, and building sequencing libraries will also be an advantage. Training will be provided as required. In addition to technical expertise, we place strong emphasis on curiosity and resilience in troubleshooting. The ideal student should have clear written and verbal communication skills alongside strong organisational skills. The student should be capable of working independently as well as within a multidisciplinary team that brings together clinicians, data scientists, and laboratory technicians. A genuine interest in translational research, particularly in bridging mechanistic insights with the development of diagnostics, vaccines, or therapeutics, will be key to thriving in this programme. |
| Subject Areas | Lung Health and Tuberculosis |
| Key Publications associated with this project |
Kasule, George W., et al. "Non-sputum-based samples and biomarkers for detection of Mycobacterium tuberculosis: the hope to improve childhood and HIV-associated tuberculosis diagnosis." European Journal of Medical Research 29.1 (2024): 502. Jenum, Synne, et al. "Approaching a diagnostic point-of-care test for pediatric tuberculosis through evaluation of immune biomarkers across the clinical disease spectrum." Scientific reports 6.1 (2016): 18520. Nogueira, Betânia MF, et al. "Diagnostic biomarkers for active tuberculosis: progress and challenges." EMBO Molecular Medicine 14.12 (2022): e14088. Swanepoel, Carmen C., et al. "Biomarker discovery for diagnosis and treatment of tuberculosis: a role for biobanking?." Journal of Biorepository Science for Applied Medicine (2015): 47-56 Schiff, H.F., et al., 2024. “Integrated plasma proteomics identifies tuberculosis-specific diagnostic biomarkers.” JCI insight, 9(8). |