Details
The aim of this project is to understand how cells form the shapes they need to engulf things from their environment. This is crucial for immune cells to capture and kill pathogens and sample their environment for antigens, but also allows stem cells and cancer cells to scavenge nutrients to support growth. The focus is on how the actin cytoskeleton is regulated, allowing cells to make the cup-shaped protrusions required to engulf microbes (phagocytosis) and extracellular fluid (macropinocytosis).
You will investigate newly-identified regulators of the cytoskeleton to understand how cells make an engulfing structure, and evolve its shape over time to close. These are fundamental and important questions about which little is known. To study this, you will use a range of cutting-edge cell biology techniques such as genetic modification using CRISPR, fluorescent protein tagging, cutting-edge live cell microscopy and phosphoproteomics.
If you join us, you will join a well-established and well-funded research group. We offer a highly supportive and inclusive environment, with an excellent track record of discovery and publication.
Students with a general interest in cell biology, the actin cytoskeleton and host-pathogen interactions are very warmly invited to apply or contact us as [email protected] for an informal chat.
About the DTP
This studentship is offered as part of the White Rose BBSRC Doctoral Training Partnership (DTP) in Mechanistic Biology, which brings together the research of the world-class molecular and cellular bioscience centres at the White Rose universities of Leeds, Sheffield and York.
Our mission is to train excellent bio-scientists who understand how living systems work
and can innovate to address global challenges, such as the impact of climate change, a healthier old age, sustainable food production, land use and energy production.
What is on offer?
This is a core/iCASE studentships for entry in October 2024.
Join us and you will receive a 4-year, funded PhD programme of research and skills training, with cross-disciplinary supervision, plus a structured programme of cohort-wide training and networking events. A highlight is the annual symposium, which is planned and delivered by students.
A unique part of your training will be the Professional Internships for PhD Students (PIPS), where you will spend three months at a host organisation of your choosing, gaining experience of work in a professional environment, and acquiring transferable skills that will be beneficial in your future career.
How to apply – Expression of Interest
Students may apply for up to three projects anywhere in the Doctoral Training Partnership (DTP). Applications will be to the DTP centrally, using an online Expression of Interest (EoI). The EoI will include:
§ CV information; not submitted separately
§ Equality, Diversity and Inclusion (EDI) data
§ Names of two referees
Deadline for EoIs is midnight Sunday 7th January 2024.
Submit EoIs using this link: https://leeds.onlinesurveys.ac.uk/white-rose-bbsrc-dtp-expression-of-interest-form
Shortlisted candidates will be required to make formal applications to the Graduate School at each institution, supplying the necessary paperwork.
Interviews will be held either Friday 2nd and Monday 5th to Friday 9th February, or Monday 19th to Friday 23rd and Monday 26th February 2024, in-person at Leeds, Sheffield and York, with a panel representing all 3 Universities. Shortlisted candidates will be notified of a specific time/date to attend. If you have applied for more than one project and are selected for interview, you will be interviewed only once.
Funding Notes
Appointed candidates will be fully funded for 4 years:
Tax-free annual stipend at the UKRI rate. The rate for starters in 2023/24 was £18,622. (Rates for 2024/25 starters are not yet available).
UKRI tuition fees – These are paid directly to the host institution.
A Research Training and Support Grant
An allowance for Fieldwork/Conference/Travel
A Professional Internship for PhD Students (PIPS) allowance
Not all projects will be funded; the DTP will appoint a limited number of candidates via a competitive process.
References
JE Lutton, HLE Coker, P Paschke, CJ Munn, JS King†, T Bretschneider†, RR Kay†. Formation and closure of macropinocytic cups in Dictyostelium. Current Biology 2023. 33 (15), 3083-3096. E6
JH Vines, H Maib, CM Buckley, A Gueho, Z Zhu, T Soldati, DH Murray, JS King†. A PI (3, 5) P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes. Journal of Cell Biology, 2023. 222 (9): e202209077
Buckley CM, Potts R, Gueho A, Vines JH, Munn CJ, Phillips BA, Gilsbach B, Nikolaev A, Soldati T, Parnell AJ, Kortholt A and King JS†. Coordinated Ras and Rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria. Current Biology, 2020. 30, 2912–2926
Buckley CM, Heath VL, Gueho A, Bosmani C, Knobloch P, Sikakana P, Personnic N, Dove SK, Michell RH, Meier R, Hilbi H, Soldati T, Insall RH† and King JS†. PIKfyve/Fab1 is required for efficient V-ATPase and hydrolase delivery to phagosomes, phagosomal killing, and restriction of Legionella infection. PloS pathogens, 2019. 15 (2), e1007551.
Gibson, J. F., Bojarczuk, A., Evans, R. J., Kamuyango, A. A., Hotham, R., Lagendijk, A. K., . . . Johnston, S. A. (2022). Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection. PLoS Pathogens, 18(4). doi: 10.1371/journal.ppat.1010389
Gibson, J. F., Prajsnar, T. K., Hill, C. J., Tooke, A. K., Serba, J. J., Tonge, R. D., . . . Johnston, S. A. (2021). Neutrophils use selective autophagy receptor Sqstm1/p62 to target Staphylococcus aureus for degradation in vivo in zebrafish. Autophagy, 17(6), 1448-1457. doi:10.1080/15548627.2020.1765521
Roddie, H. G., Armitage, E. L., Coates, J. A., Johnston, S. A., & Evans, I. R. (2019). Simu- dependent clearance of dying cells regulates macrophage function and inflammation resolution. PLoS Biology , 17(5). doi:10.1371/journal.pbio.2006741
Evans, R. J., Pline, K., Loynes, C. A., Needs, S., Aldrovandi, M., Tiefenbach, J., . . . Johnston, S. A. (2019). 15-keto-prostaglandin E2 activates host peroxisome proliferator-activated receptor gamma (PPAR-γ) to promote Cryptococcus neoformans growth during infection. PLoS Pathogens, 15(3). doi:10.1371/journal.ppat.1007597