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 | Antiretroviral therapy has transformed HIV/AIDS from a fatal disease into a manageable condition, but it is not curative. The virus uses a sophisticated strategy to persist: it integrates its genetic material into human DNA and hides in long-lived cells, forming 'latent reservoirs' that remain invisible to both therapy and the immune system. These hidden reservoirs are the central barrier to achieving an HIV-1 cure - the long-sought 'holy grail' of HIV research. The leading cure concept, 'shock-and-kill', uses drugs called latency-reversing agents (LRAs) to force the virus out of hiding ('shock'), followed by immune clearance of infected cells ('kill'). However, current LRAs have not reduced reservoir size in patients. Some even weaken natural antiviral defences, and viral proteins contribute to blocking immune clearance. Our team' s research has revealed new insights into these barriers. We have developed unique laboratory models - latently infected T-cells with precisely mapped viral integration sites - that allow us to study HIV-1 latency and immune recognition in unprecedented detail. In this project, we will identify cellular host programs which HIV-1 induces during reactivation, determine how viral accessory proteins sabotage immune responses; use cutting-edge CRISPR screens to uncover human genes that positively or negatively shape HIV-1 latency, and extend these studies to HIV-1 subtype C, the dominant subtype in Sub-Saharan Africa but largely neglected in cure research. This work will increase our understanding of the biology of HIV-1 persistence and fill knowledge gaps to bring the field closer to a safe and effective cure for HIV-1. |
| Where does this project lie in the translational pathway? | T1 - Basic Research,T2 - Human /Clinical Research |
| Methodological Aspects | 1. Fluorescence-activated cell sorting (FACS) (quantitative) 2. CL3 work 3. Single cell RNA-sequencing (quantitative) 4. Isolation and culture of human primary target cells of HIV-1 infection 5. Gene editing in cells 6. Statistical analyses (quantitative) 7. Bioinformatics (quantitative) |
| Expected Outputs | Publications in peer-reviewed journals, conference abstracts as well as proof-of-concept data to support grant applications for further research towards HIV-1 cure and further develop patent applications. |
| Training Opportunities | Hands-on training in all above-mentioned methods by experienced members of the group. Furthermore, the student will be encouraged to learn additional methods beneficial to the project in the context of collaborations, and will have full access to soft skills trainings (time management, communication, presentation etc.). They will also be given opportunities to attend national and international conferences to present their work. |
| Skills Required | Background in virology and/or immunology is desirable but not a must. Interest in conducting fundamental research in order to contribute to close a clinical knowledge gap (HIV-1 cure). Scientific curiosity and strong decision-making skills. |
| Subject Areas | HIV/AIDS |
| Key Publications associated with this project |
https://www.biorxiv.org/content/10.1101/2025.08.06.668975v1 https://www.biorxiv.org/content/10.1101/2020.05.04.075119v3 https://doi.org/10.4049/jimmunol.2100685 |