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 | Mpox is a zoonotic disease caused by the monkeypox virus (MPXV). Historically, mpox was endemic to Central and West Africa, but since May 2022, the number of mpox cases has increased with the rapid expansion in nonendemic countries; it was declared the first mpox public health emergency of international concern (PHEIC) by the World Health Organisation (WHO). Since then, >100,000 cases of mpox and >200 deaths have been described in >120 countries not previously considered mpox endemic. On August 14, 2024, a second mpox PHEIC was declared by the WHO, and the Democratic Republic of the Congo (DRC) reported the highest number of suspected cases globally, with more than 800 deaths. To confirm a clinical diagnosis, WHO advises testing as soon as possible in persons who fit the suspected case definition. Current diagnostic is performed by laboratory-based real-time PCR, which requires costly equipment, up-front DNA extraction, and skilled personnel and is only available in specialised laboratories, making rapid detection of cases during outbreaks more challenging. Despite the availability of point-of-care (POC) tests in the market for the detection of mpox antigens, the sensitivity is currently too low to be suitable for the detection of cases. Analytical sensitivity using viral cultures and recombinant antigen has proven to be enough to detect clinically relevant viral loads however, the clinical sensitivity of these devices has been inexpertly proven to be too poor. The reason for this poor correlation in antigen detection sensitivity between mpox clinical samples and mpox viral isolates is still uncertain, but it has been hypothesised that it is due to the presence of inaccessible antigen in clinical samples. The availability of sensitive point-of-care (POC) tests to rapidly detect infected patients would speed isolation and management of patients. Using LSTM’s and Lancaster University’s unique resources and expertise in antibody discovery and diagnostics development, this project will focus on the development of mpox antibodies using novel technologies to improve the detection of difficult targets. This project includes the analysis of antigen availability on mpox clinical samples, the discovery of antibodies and the development of novel diagnostics. |
| Where does this project lie in the translational pathway? | T1 - Basic Research |
| Methodological Aspects | The student will be trained in advanced mass-spectrometry techniques for the analysis of antigen targets in clinical samples. For antibody discovery, we will primarily use in vitro phage- and yeast-display antibody libraries to allow the discovery of new monoclonal antibodies. There is potential for the student to incorporate in silico approaches for the de novo design of protein binders. Following this, the student will be trained in recombinant expression and purification of monoclonal antibodies and/or de novo designed proteins, before their use in a range of in vitro and in vivo assays to assess sensitivity and specificity. The candidate will also be trained in the development of rapid diagnostic tests, such as lateral flow assays and biosensor detection. Quantitative elements are incorporated throughout this project, including statistical analysis of quantitative in vitro assays, and through bioinformatics techniques (sequence alignment, structural modelling of proteins). |
| Expected Outputs | The expected outputs for this project will be high-impact papers due to the importance of this pathogen and the novelty of the project. Discovered antibodies and newly developed diagnostics will have the potential for patent filing and lead to further progress through the development pipeline for commercialisation. We anticipate at least two first-author research papers from the student, one paper on the methodological aspects of the antibody discovery pipelines and a second one on the diagnostic accuracy of the developed diagnostic device. Additional co-authorships are likely through collaborative studies with partner laboratories. The body of work will directly underpin future grant applications to MRC/UKRI, NIHR, etc and others, strengthening bids not only in the diagnostic space but also in therapeutic monoclonals. 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. |
| Training Opportunities |
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| Skills Required | We expect the student to possess strong organisational and problem-solving aptitude. The student would benefit from basic skills in molecular biology and biotechnology; however, this is not essential, as we will provide in-depth training in all techniques. |
| Subject Areas | Neglected Tropical Diseases |
| Key Publications associated with this project |
Shara-Nshombo, Elie, et al. Diagnostic Accuracy of 3 Mpox Lateral Flow Assays for Antigen Detection, Democratic Republic of the Congo and United Kingdom. Emerging Infectious Diseases 31.6 (2025): 1140. Laidlaw, Stephen M., et al. Detection of mpox and other orthopoxviruses using a lateral flow device as a point-of-care diagnostic. Microbiology spectrum 13.4 (2025): e02456-24. Thakur, Abhimanyu. Point-of-care biosensors for monkey pox detection. LabMed Discovery (2024): 100025. Menzies SK, Patel RN, Ainsworth S. Practical progress towards the development of recombinant antivenoms for snakebite envenoming. Expert Opin Drug Discov. 2025 Jun;20(6):799-819. doi: 10.1080/17460441.2025.2495943. Epub 2025 Apr 29. PMID: 40302313. Torres SV., et al. De novo designed proteins neutralise lethal snake venom toxins. Res Sq [Preprint]. 2024 May 17:rs.3.rs-4402792. doi: 10.21203/rs 3.rs-4402792/v1. PMID: 38798548; PMCID: PMC11118692. |