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Regulation of synaptic protein function by protein palmitoylation


   School of Biosciences

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  Dr M Collins  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

Palmitoylation (S-acylation), the only known reversible lipid modification of proteins, is an important regulator of protein localisation and function. It is involved in a plethora of cellular processes including protein trafficking, stability and signalling and is therefore important for all cell types, and organisms from yeast to humans. Palmitoylation is mediated by a family of 23 enzymes (protein acyl transferases (PATs)) in humans. Many of these enzymes have been shown to regulate important aspects of cell biology and in particular in neuronal cells where palmitoylation of receptors and associated proteins regulate synaptic plasticity and therefore functions such as learning and memory. Indeed, mutations in several of these enzymes have been implicated in the pathophysiology of neurological disorders including a plasma membrane localised synaptic PAT, DHHC5 which is a schizophrenia risk gene.

Recently, we uncovered a novel and central role for DHHC5 in the regulation of cell-cell adhesion in epithelial cells. In this project, the student will investigate the role of DHHC5 in the regulation of synaptic palmitoylation and trans-synaptic adhesion. This project will use proteomic approaches that we are developing to identify synaptic substrates of DHHC5 and investigate how palmitoylation of selected substrates regulates their stability, trafficking and function. This interdisciplinary project will utilise a range of experimental approaches including cell culture, molecular and cell biology, biochemistry and state-of-the-art quantitative mass spectrometry. The student will be given in-depth training in all of these methods and will benefit from collaborations with other groups within the department and across the faculty.

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit www.sheffield.ac.uk/sgs to learn more.


Funding Notes

This position is for self funded or externally funded students only.

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/postgraduate/research/apply/applying

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.

References

https://www.sheffield.ac.uk/biosciences/people/bms-staff/academic/mark-collins
1. Woodley KT, Collins MO. Regulation and function of the palmitoyl-acyltransferase ZDHHC5. FEBS J. 2021 Jan 8.
2. Woodley KT, Collins MO. S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion. EMBO Reports. 2019 Aug 12:e47472.
3. Collins MO, Woodley KT, Choudhary JS. Global, site-specific analysis of neuronal protein S-acylation. Sci Reports. 2017 Jul 5;7(1):4683.
4. Fernández E, Collins MO, Frank RAW, Zhu F, Kopanitsa MV, Nithianantharajah J, Lemprière at al. Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence. Cell Reports. 2017 Oct 17;21(3):679-691.
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