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Molecular dissection of activity-dependent neuronal signalling pathways using quantitative proteomics

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Recent proteomic investigations have identified several thousand proteins in biochemically purified synapses and have uncovered multiprotein complexes essential for synapse function. Through these experiments, we have found that many of these synaptic genes are associated with over 100 neurological diseases, highlighting the need for a better a molecular understanding of synapses.
Many genes/proteins have been implicated in different aspects of synaptic plasticity in single gene/low-throughput studies. However, few studies have taken unbiased approaches to measure global synaptic responses at the protein level and therefore it is not clear what the relative significance of a change in expression or phosphorylation of a single protein in the context of the synapse proteome as a whole. The global analysis of early to late signalling events in synaptic stimulation time-course experiments will also add an important temporal dimension to our understanding of signal transduction and processing at synapses.
Furthermore, the extent and importance of receptor-mediated signalling pathway cross-talk is poorly characterised; the molecular dissection of post-translational modification cross-talk at the synapse will be important to understand how signal integration occurs through complex signalling networks. The use of mass spectrometry-based proteomics has great potential to further our understanding of synaptic signalling pathways in an unbiased, quantitative and temporal manner.
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.

The aims of the project include the following.
1) Identify protein expression and post-translational modification (e.g. phosphorylation, ubiquitination and palmitoylation) changes that occur after established stimulation paradigms in neuronal cell culture.
2) Examine temporal features and cross talk of signalling pathways in time course experiments
3) Characterise the function of activity dependent post-translational modifications on selected disease-relevant genes

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

Entry requirements
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

References
Collins MO, Woodley KT, Choudhary JS. Global, site-specific analysis of neuronal protein S-acylation. Sci Rep. 2017 Jul 5;7(1):4683.

Fernández E, Collins MO, Frank RAW, Zhu F, Kopanitsa MV, Nithianantharajah J, Lemprière SA, Fricker D, Elsegood KA, McLaughlin CL, Croning MDR, Mclean C, Armstrong JD, Hill WD, Deary IJ, Cencelli G, Bagni C, Fromer M, Purcell SM, Pocklington AJ, Choudhary JS, Komiyama NH, Grant SGN. Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence. Cell Rep. 2017 Oct 17;21(3):679-691.

Bayés A, van de Lagemaat LN, Collins MO, Croning MD, Whittle IR, Choudhary JS, Grant SG. (2011). Characterization of the proteome, diseases and evolution of the human postsynaptic density. Nature Neuroscience. Jan;14(1):19-21.

Cox J, Mann M. (2011). Quantitative, high-resolution proteomics for data-driven systems biology. Annual Review of Biochemistry 2011;80:273-99.

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

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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