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Regulation of SNARE complex assembly and function by the lysine deacetylase Sirtuin-2


Project Description

Sirtuin-2 (Sirt2) is a lysine deacetylase that regulates acetylation levels of cytoplasmic proteins and has established roles in neurodegeneration, cancer and infection. Recent evidence suggests a role for Sirt2 in regulating vesicle trafficking and secretion. The aim of this project is to investigate how acetylation regulates the stability of SNARE proteins as well as SNARE complex formation. This will be achieved by testing the ability of acetylation site mutants to drive membrane fusion in assays that measure constitutive secretion and endocytic recycling. Furthermore, the effect of SNARE acetylation on cleavage by Botulinum Neurotoxin will be investigated. The cross-talk between acetylation and ubiquitination will be determined using mass spectrometry based proteomic analysis of Sirt2 knockout mice. The student will be given in-depth training in molecular cell biology and mass spectrometry based-proteomics and will benefit from collaborations with other groups within the department. This is a multidisciplinary project between the Collins and Peden labs that will exploit cutting-edge methods to generate high-quality quantitative data to probe novel mechanisms of SNARE complex regulation.

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 http://www.sheffield.ac.uk/sgs to learn more.

Funding Notes

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: View Website
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

Woodley KT, Collins MO. S-acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion. EMBO Rep. 2019 Aug 12:e47472.

Ampah K.K., Greaves J., Shun-Shion A.S.M., Asnawi A.W.B.A., Lidster J., Chamberlain L.H, Collins M.O. and Peden A.A. S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19. 2018 J. Cell Sci. doi:10.1242/jcs.212498.

Gordon D.E., Chia J., Jayawardena K., Antrobus R., Bard F., Peden A.A. VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. 2017 PLoS Genetics. doi: 10.1371/journal.pgen.1006698.

http://www.sheffield.ac.uk/bms/research/collins/index

https://www.sheffield.ac.uk/bms/research/peden

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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