An integrated molecular, cell and proteomic analysis of palmitoylation in neurons
Palmitoylation, the only known reversible lipid modification of proteins, is an important regulator of protein localisation and function. It affects 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. The extent to which this reversible post-translational modification is employed and how the specificity of the palmitoylation machinery is encoded remains to be determined.
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 regulates synaptic plasticity and therefore functions such as learning and memory. Indeed, several of these enzymes have been implicated in the pathophysiology of neurological disorders from Huntington’s disease to intellectual disability and schizophrenia.
It is not well understood which proteins are modified by individual PATs in cells, how they can selectively recognise substrate proteins and what effect palmitoylation has on the function of these proteins. This project will use proteomic approaches that we have recently developed to identify substrates of protein acyl transferases 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.
This research will further our understanding of how proteins dynamically associate with membranes and how this affects their function in health and disease.
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.
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, 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*.
Mark O. Collins Keith Woodley and Jyoti S. Choudhary. Global, site-specific analysis of neuronal protein S-acylation. Scientific Reports. 2017. Jul 5;7(1):4683.
Fukata Y, Fukata M. (2010). Protein palmitoylation in neuronal development and synaptic plasticity. Nature Reviews Neuroscience. Mar;11(3):161-75.
Jones ML, Collins MO, Goulding D, Choudhary JS & Rayner JC (2012). Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis. Cell Host & Microbe, 12(2), 246-258.
Cox J, Mann M. (2011). Quantitative, high-resolution proteomics for data-driven systems biology. Annual Review of Biochemistry 2011;80:273-99.
How good is research at University of Sheffield in Biological Sciences?
FTE Category A staff submitted: 44.90
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