Functional genomics to identify pathogenic protein function
The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 150 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.
The Thorpe lab specialises in yeast genetics and genomics and has recently explored these tools to study the function of viral proteins from the SARS-CoV-2 virus. The lab is fully equipped with state of the art tools for functional genomics. Including robotic pinning tools to aid high throughput screens.
Training and development
Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.
Specifically in the Thorpe lab you will learn genetics, genomics and cell biology. Including fluorescence imaging and high-content image analysis and high-throughput yeast genetics. You will learn to present scientific work both in talks and in written work.
Infectious disease remains one of the largest causes of mortality and morbidity across the world. To derive new pharmaceutical drugs that target these infectious diseases requires the identification of drugs that specifically block the pathogen life cycle. To facilitate drug discovery, an assay system is needed to identify the function of specific pathogenic proteins, e.g., screening for drugs which target one of the two SARS-CoV-2 proteases.
However, this approach is challenging when the functions of many of the pathogen proteins are unknown. We propose to bypass this problem by rendering yeast sensitive to individual viral proteins by associating them with endogenous yeast proteins. This will create a robust, cheap and rapid system for high-throughput drug screens. We have developed a high-throughput protein association system that allows us to tether any pathogen protein with every protein in the yeast proteome in vivo (Berry et al., 2016; Ólafsson & Thorpe, 2017), and rapidly identify those that cause lethality in yeast. This system is called synthetic physical interaction (SPI) and has been used effectively for SAR-Cov-2, the causative agent of Covid-19 (Klemm et al. 2021).
We will screen several pathogen proteins using the SPI system. First, Vpr and Vpu proteins from human immunodeficiency virus that have largely uncharacterised effects upon the cell cycle and intracellular trafficking respectively. Second, the PtpA, PrpB and Rv1468c, which are key proteins for host effects of Mycobacterium tuberculosis the causative bacteria of tuberculosis.
Finally, we will screen two secreted proteins from the malaria parasite Plasmodium falciparum, PfAK2 and PfARF1, which affect the vacuole and Golgi respectively. Thus, these synthetic yeast strains will enable robust, rapid, high-throughput drug screening for anti-pathogenic drugs.
This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.
Eligibility and applying
- Be Chinese students with a strong academic background.
- Students must hold a PR Chinese passport.
- Applicants can either be resident in China at the time of application or studying overseas.
- Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.
Please refer to the CSC website for full details on eligibility and conditions on the scholarship.
Applicants are required to provide evidence of their English language ability. Please see our English language requirements page for details.
The deadline for applications to Queen Mary is 30th January 2022. Applicants will need to complete an online application form by this date to be considered, including a CV, personal statement and qualifications. Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CSC scholarship (as well as any academic conditions still required to meet our entry requirements).
Once applicants have obtained their offer letter from Queen Mary they should then apply to CSC for the scholarship by the advertised deadline with the support of the project supervisor. For September 2022 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2022.
Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme.
- Berry, L. K., Ólafsson, G., Ledesma-Fernández, E. & Thorpe, P. H. Synthetic protein interactions reveal a functional map of the cell. eLife 5, 576 (2016).
- Klemm, C. et al. Forced association of SARS-CoV-2 proteins with the yeast proteome perturb vesicle trafficking. Microbial Cell 8, 280 (2021).
- Ólafsson, G. & Thorpe, P. H. Rewiring the Budding Yeast Proteome using Synthetic Physical Interactions. in Methods in Molecular Biology vol. 1672, 599–612 (Humana Press, 2017).