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Personal profile

Personal Statement

PROTEIN S-ACYLATION IN HEALTH AND DISEASE

S-acylation (aka palmitoylation), the reversible attachment of fatty acids onto cysteine residues, regulates a diverse array of proteins and impacts fundamental cellular processes such as signalling, membrane traffic, communication, and growth and division. Defects in S-acylation are linked with cancer, diabetes, and CNS disorders such as intellectual disability, epilepsy, Huntington’s disease and neuronal ceroid lipofuscinosis. In addition, S-acylation is required for infection and virulence of some viruses and parasites. As a result, there is growing interest in the therapeutic potential of targeting the S-acylation machinery, with a major goal being the development of isoform-selective inhibitors against the 23 zDHHC S-acyltransferase enzymes.

RESEARCH IN THE CHAMBERLAIN LAB

The research that we are undertaking aims to unravel the multitude of functions that S-acylation plays in cellular pathways, in particular, signalling and membrane traffic. In addition, we aim to understand how defects in S-acylation contribute to disorders such as intellectual disability, epilepsy, neurodegeneration, cancer and diabetes. Through this work we hope to identify novel drug targets and new drug treatments for these conditions. We use a wide range of techniques including chemical biology (click chemistry), confocal microscopy, proteomics, and behavioural analyses.

Our research falls into two major programmes:

1. S-acylation and cell function in health and disease

(i) How does dynamic S-acylation of key signalling and trafficking proteins regulate cell pathways and how does disruption of this process cause disease?

(ii) What are the molecular effects of S-acylation that underlie protein regulation?

(iii) Does acyl chain heterogeneity provide functionally distinct pools of the same protein?

2. The zDHHC family of S-acyltransferases

(i) What are the substrate networks of individual zDHHC enzymes, and how is enzyme-substrate specificity encoded?

(ii) How do zDHHC enzymes select specific acyl-CoAs from a mixed population?

(iii) How do multiple zDHHC enzyme isoforms coordinate protein S-acylation at the level of a single intracellular organelle?

(iv) What are the cellular and molecular changes that underlie disease phenotypes caused by ZDHHC mutations?

(v) Can we develop isoform-selective chemical modulators of the zDHHC enzyme family?

 

RESEARCH OPPORTUNITIES


We would be delighted to hear from post-doctoral researchers interested in developing fellowhsip proposals that can be hosted in our lab. We can offer support and mentorship for fellowship applications.

We are also happy to speak with prospective PhD students who have secured funding.

All enquiries can be directed to luke.chamberlain@strath.ac.uk

Education/Academic qualification

Doctor of Philosophy, University of Liverpool

Bachelor of Science, University of Edinburgh

Keywords

  • palmitoylation
  • S-acylation
  • exocytosis
  • lipid raft
  • caveolae
  • membrane traffic

Fingerprint Dive into the research topics where Luke Chamberlain is active. These topic labels come from the works of this person. Together they form a unique fingerprint.

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Membranes Medicine & Life Sciences
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Enzymes Medicine & Life Sciences

Network Recent external collaboration on country level. Dive into details by clicking on the dots.

Projects 2011 2022

Research Output 2008 2018

1 Citation (Scopus)

Disruption of the Zdhhc9 intellectual disability gene leads to behavioural abnormalities in a mouse

Kouskou, M., Thomson, D. M., Brett, R. R., Wheeler, L., Tate, R. J., Pratt, J. A. & Chamberlain, L. H., 31 Oct 2018, In : Experimental Neurology. 308, p. 35-46 12 p.

Research output: Contribution to journalArticle

Open Access
File
Intellectual Disability
Acylation
Corpus Callosum
Protein S
Genes
3 Citations (Scopus)

Fam49/CYRI interacts with Rac1 and locally suppresses protrusions

Fort, L., Batista, J. M., Thomason, P. A., Spence, H. J., Whitelaw, J. A., Tweedy, L., Greaves, J., Martin, K. J., Anderson, K. I., Brown, P., Lilla, S., Neilson, M. P., Tafelmeyer, P., Zanivan, S., Ismail, S., Bryant, D. M., Tomkinson, N. C. O., Chamberlain, L. H., Mastick, G. S., Insall, R. H. & 1 othersMachesky, L. M., 24 Sep 2018, In : Nature Cell Biology. 20, p. 1159-1171 13 p.

Research output: Contribution to journalArticle

Open Access
File
Pseudopodia
Cicatrix
Actins
Optogenetics
Chemotaxis

Thesis

Exploring the links between the ZDHHC9 gene and intellectual disability

Author: Kouskou, M., 1 Dec 2017

Supervisor: Chamberlain, L. (Supervisor) & Pratt, J. (Supervisor)

Student thesis: Doctoral Thesis

Palmitoylation in neurodegeneration : analysis of cysteine-string protein mutants linked with neuronal ceroid lipofuscinosis

Author: Diez Ardanuy, C., 1 Oct 2016

Supervisor: Chamberlain, L. (Supervisor) & Bushell, T. (Supervisor)

Student thesis: Doctoral Thesis