Fixed-term

Details In multi-cellular organisms, coordinated cell death (e.g. apoptosis) and cell replacement is critical for tissue recovery in response to stress or damage. Although there is not much known about this process at the cellular and molecular level, recent studies including ours have discovered that apoptotic cells can actively induce compensatory proliferation of surrounding cells through a non-apoptotic function of caspases, a family of cysteine-proteases that normally execute apoptosis. This research aims to dissect the molecular anatomy of compensatory cell proliferation following activation of apoptosis. By taking advantages of Drosophila as a model organism, we have developed unique assays to systematically identify and characterize regulators of compensatory cell proliferation. Because apoptosis-induced compensatory cell proliferation has been observed in tissue regeneration and tumorigenesis in multiple organisms including mammals, identification of its underlying regulatory mechanisms in Drosophila will significantly impact our understanding of its physiological role in tissue repair as well as its pathological role in multiple human diseases including cancer. State-of-the-art technologies in Cell Biology, Molecular Biology, Advanced Microscopy Imaging and Drosophila Genetics are employed in this research. Please provide a brief summary of your research experience when making inquiries or registering interest via FindAPhD. Alternatively, you can email the project’s lead supervisor directly with a CV outlining your education and relevant practical experience. To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each school, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus, at: https://www.birmingham.ac.uk/study/postgraduate Please find additional funding text below. For further funding details, please see the ‘Funding’ section. The School of Biosciences offers a number of UK Research Council (e.g. BBSRC MIBTP, https://www.birmingham.ac.uk/research/activity/mibtp/index.aspx) PhD studentships each year. Fully funded research council studentships are available to both UK nationals and overseas students. The deadline for applications for research council studentships is typically in early January each year. Each year we also have a number of fully funded Darwin Trust Scholarships. These are provided by the Darwin Trust of Edinburgh and are for non-UK students wishing to undertake a PhD in the general area of Molecular Microbiology. The deadline for this scheme is also typically in early January each year. Funding Notes All applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications at any time from students able to find their own funding or who wish to apply for their own funding (e.g. Commonwealth Scholarship, Islamic Development Bank). The postgraduate funding database provides further information on funding opportunities available at: https://www.birmingham.ac.uk/postgraduate/courses/research/bio/biosciences.aspx Applications to our competitive funding are normally closed in early January each year. Applicants with their own funding are welcome to apply at any time but must go through the same selection process. Please contact the project’s lead supervisor for further information. References 1) Farrell L, Puig-Barbe A, Haque MI, Amcheslavsky A, Yu M, Bergmann A and Fan Y. (2022) Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation. PLoS Genetics 18(12): e1010533. 2) Fan Y.*, Wang S., Hernandez J., Yenigun V.B., Hertlein G., Fogarty C.E., Lindblad J.L. and Bergmann A.* (2014) A model for identification of genes involved in apoptosis-induced proliferation in Drosophila. PLoS Genetics 10(1): e1004131. (*corresponding authors) 3) Fan, Y., and Bergmann, A. (2008) Distinct mechanisms of apoptosis-induced compensatory proliferation in proliferating and differentiating tissues in the Drosophila eye. Dev Cell 14, 399-410. Apply Now

Details Proteins are essential components of cells, and the proteome must be effectively regulated to maintain cellular integrity. A critical contributory step to proteome function is protein synthesis, where mRNAs are translated into polypeptides by the ribosome. However, problems can arise during this process, leading to the production of “bad” proteins that negatively impact cellular function. Defective mRNAs and proteins must be recognised and destroyed, but, surprisingly, mechanisms controlling co-translational protein quality in plants are still largely unknown. We recently identified a family of E3 ubiquitin ligases in the model plant Arabidopsis that function at the interface of mRNA translation and protein destruction. This project will investigate the hypothesis that these ligases are components of an expanded and plant-specific “toolkit” that provides dynamic and stress-responsive functions in translational quality control. There are several key areas where a PhD candidate would focus their investigations: (1) Defining how these E3 ligases dynamically associate with ribosomes, proteasomes and other cellular machineries to form ‘translasomes’ that act as quality surveillance hubs. (2) Characterising their direct proteolytic and mRNA targets. (3) Characterising how their activity is regulated in response to changing translational demands of the cell under optimal and challenged situations. (4)Determining how they contribute to the control of global and stress-responsive mRNA translation and degradation. The research will be largely molecular based and will also include ‘omics’ approaches. The PhD candidate will therefore gain expertise in a wide range of cutting edge and transferable techniques. How to apply: To apply, please follow this link, make an account, and submit an application via the university online admissions portal. This link is unique to the MIBTP programme; please do not use any other link to apply to this project or your application may be rejected: https://sits.bham.ac.uk/urd/sits.urd/run/siw_ipp_lgn.login?process=siw_ipp_app&code1=FR167D&code2=0005 Funding Notes This project is competition-funded via the MIBTP doctoral training partnership. See project description here: https://warwick.ac.uk/fac/cross_fac/mibtp/phd/supervisors/DGibbs/#protein_synthesis Please contact Professor Daniel Gibbs with a CV and cover letter BEFORE applying to this project. Apply Now

Details Every day, we make choices that involve balancing opportunities with risks—but what’s actually happening in our brains as we make these decisions remains largely unknown. A central mystery in neuroscience is how the brain evaluates conflicting options and prioritizes specific actions. Evidence suggests there are sex differences in decision-making and unique vulnerabilities to neurological disorders across genders. Therefore, understanding how the brain makes decisions across contexts and genders holds important medical, economical, and societal benefits. Studying decision-making in mammals is challenging due to the brain’s complexity, but it is feasible in the fruit fly Drosophila, where single cells and circuits can be easily observed and manipulated. Capitalising on these advantages, we discovered a fascinating brain mechanism that allows flies prioritise behaviours during conflicting situations (Cazale-Debat et.al Nature, 2024 doi: 10.1038/s41586-024-07890-3). When animals, including humans, are deeply focused on something they desire—they may become less aware of potential dangers around them. This phenomenon, often referred to as “love blindness,” is a widespread behavioural tendency where the pursuit of a valued reward, like a mate, can overshadow possible risks. In the animal world, this kind of focus can help increase the chances of finding a mate and reproducing, but it also makes individuals more vulnerable to threats, such as predators. In our study, we explored how the brain balances risk and reward during courtship, focusing on male fruit flies. We discovered a neural mechanism controlled by dopamine, a chemical linked to reward and pleasure, which allows the flies to reduce their sensitivity to danger as they get closer to mating. In the early stages of courtship, visual signals alert the flies to nearby threats, activating certain neurons that cause the flies to stop courting. This response is mediated by serotonin, another brain chemical that temporarily inhibits the courtship drive to ensure survival. However, as the male flies advance in the courtship process, the brain gradually shifts gears. Dopamine levels rise, which reduces the response to threats, allowing the flies to stay focused on courtship instead of fleeing from danger. By tracking brain activity, we observed that the closer the flies get to mating, the higher the dopamine levels rise, eventually blocking the pathway that would normally alert them to visual threats. This allows the flies to “tune out” distractions and prioritise mating. In essence, dopamine acts as a sensory filter, adjusting the flies’ perception of threats based on their proximity to achieving their goal. This filtering system enables the brain to prioritise between competing actions, choosing reproduction over survival when it matters most. This PhD project will take this discovery further, aiming to answer key questions: (i) Does this dopamine-driven filtering mechanism also exist in females, and are there sex-specific differences? (ii) Is this neural mechanism applicable to other high-stakes decisions beyond mating versus predator avoidance? (iii) Is this neural mechanism an evolutionarily conserved strategy? As a PhD student on this project, you’ll work at the cutting edge of neuroscience, using state-of-the-art techniques including advanced genetics, neural circuit tracing/connectomics, multiphoton imaging to capture neural activity in live, synaptic tracing, behaving flies, optogenetics, CRISPR for gene editing, and custom coding for data analysis. You will collaborate with researchers working in Germany, UK and Switzerland. This project offers an unprecedented opportunity to uncover decision-making processes during conflicts at remarkable molecular, cellular, and neural circuit level, revealing fundamental principles of brain function across species and sexes. For more information about the Rezaval lab and research please visit: https://www.rezavallab.org/ Please contact Prof Rezaval directly with a cover letter outlining your interest, your background, and why you wish to join her lab in particular. References Mating proximity blinds threat perception. Nature (2024). https://doi.org/10.1038/s41586-024-07890-3. Laurie Cazalé-Debat*, Lisa Scheunemann*, Megan Day, Tania Fernandez-d.V. Alquicira, Anna Dimtsi, Youchong Zhang, Lauren A Blackburn, Charles Ballardini, Katie Greenin-Whitehead, Eric Reynolds, Andrew C Lin$, David Owald, and Carolina Rezaval. A neuronal mechanism controlling the choice between feeding and sexual behaviors in Drosophila. Cheriyamkunnel SJ*, Rose S*, Jacob PF, Blackburn LA, Glasgow S, Moorse J, Winstanley M, Moynihan PJ, Waddell S, Rezaval C. Curr Biol. 2021 Neuroscience: How the brain prioritizes behaviors. Barajas-Azpeleta, R, Tastekin I and Ribeiro C. Curr Biol. 2021. Bellen, H., Tong, C. & Tsuda, H. 100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future. Nat Rev Neurosci 11, 514–522 (2010). https://doi.org/10.1038/nrn2839