The cells of our immune system perform key roles, such as shaping our bodies as they develop, fighting-off infection, and repairing tissues. However, uncontrolled immune responses can lead to autoimmunity and contribute to multiple human pathologies. Furthermore, as we age, there is a decline in the ability of our immune system to fight infection, clear senescent cells and repair our degenerating bodies. This process is termed immunosenescence and is currently viewed as a major driver of the ageing process. An ageing population coupled with the emergence of pathogens resistant to drugs makes understanding how adequate immunity is balanced with autoimmunity during ageing one of the critical questions of our time. This work will also provide an insight into ways we can manipulate host immune systems to combat drug-resistant pathogens.
This project will use Drosophila models of immunity to understand how blood cell numbers and activity are controlled at a genetic level and in turn how these are affected by ageing. You, the student, will benefit from a wealth of data collected in the supervisors’ labs on this topic. This includes detailed information on the genetics underlying blood cell biology, fecundity, longevity and neurodegeneration. It will be particularly interesting to now experimentally test the genes we identified that regulate more than one of these processes. In parallel, we have very recently demonstrated the existence of functionally-distinct macrophage subpopulations in Drosophila. As part of these studies we have developed novel genetic tools to manipulate these macrophage subpopulations in vivo and the student will be the first in applying these to understand immunology and its interplay with ageing.
The student will test identified candidate genes and mechanisms using genetic manipulations readily available in the fly (mutant analysis/tissue-specific RNAi/CRISPR). In addition to the unparalleled genetic manipulation available in the fly model we will also apply stare-of-the-art live imaging approaches to follow blood cell behavior live and in vivo. This project will therefore involve Drosophila genetics, molecular biology approaches (e.g. cloning of candidate genes, transgenesis, expression analysis, PCR genotyping), and live imaging of blood cells in vivo and ex vivo using Sheffield’s state-of-the-art imaging facilities. You will be part of a multidisciplinary, collaborative and successful team consisting of over 6 PhD students, multiple technicians and collaborators. We will encourage you to take full advantage of the excellent training on offer via the Dimen DTP, present your data at international conferences and shape your PhD project’s direction.
University webpage https://www.sheffield.ac.uk/iicd/profiles/iwanevans
Lab website http://iwanrevans.weebly.com/
University webpage https://www.sheffield.ac.uk/aps/staff-and-students/acadstaff/simons
Lab website http://www.simons-lab.group.shef.ac.uk/
Please do not hesitate to get in touch to discuss the project in more detail or to find out more about us and our labs via [email protected]
or [email protected]
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website: http://www.dimen.org.uk/
1. Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution. Roddie et al., PLoS Biol (2019) 17:e2006741
2. Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response. Weavers et al., Cell (2016) 165:1658
3. Comparative idiosyncrasies in life extension by reduced mTOR signalling and its distinctiveness from dietary restriction. Garratt et al., Aging Cell (2016) 15, 737-743