Professor Luke Chamberlain

Strathclyde Institute of Pharmacy and Biomedical Sciences

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

Publications

S-acylation of Sprouty and SPRED proteins by the S-acyltransferase zDHHC17 involves a novel mode of enzyme-substrate interaction
Butler Liam, Locatelli Carolina, Allagioti Despoina, Lousa Irina, Lemonidis Kimon, Tomkinson Nicholas C O, Salaun Christine, Chamberlain Luke H
Journal of Biological Chemistry Vol 299 (2022)
https://doi.org/10.1016/j.jbc.2022.102754
Development of a novel high-throughput screen for the identification of new inhibitors of protein S-acylation
Salaun Christine, Takizawa Hiroya, Galindo Alex, Munro Kevin R, McLellan Jayde, Sugimoto Isamu, Okino Tomotaka, Tomkinson Nicholas CO, Chamberlain Luke H
Journal of Biological Chemistry Vol 298 (2022)
https://doi.org/10.1016/j.jbc.2022.102469
Regulatory effects of protein S-acylation on insulin secretion and insulin action
Chamberlain Luke H, Shipston Michael J, Gould Gwyn W
Open Biology Vol 11 (2021)
https://doi.org/10.1098/rsob.210017
Accessory proteins of the zDHHC family of S-acylation enzymes
Salaun Christine, Locatelli Carolina, Zmuda Filip, Cabrera González Juan, Chamberlain Luke H
Journal of Cell Science Vol 133 (2020)
https://doi.org/10.1242/jcs.251819
Identification of key features required for efficient S-acylation and plasma membrane targeting of Sprouty-2
Locatelli Carolina, Lemonidis Kimon, Salaun Christine, Tomkinson Nicholas C O, Chamberlain Luke H
Journal of Cell Science Vol 133 (2020)
https://doi.org/10.1242/jcs.249664
Regulatory effects of post-translational modifications on zDHHC S-acyltransferases
Zmuda Filip, Chamberlain Luke H
Journal of Biological Chemistry Vol 295, pp. 14640-14652 (2020)
https://doi.org/10.1074/jbc.REV120.014717

More publications

Professional activities

Krzysztof Wypijewski
Host
21/9/2022
UKRI Medical Research Council (External organisation)
Advisor
1/9/2021
UKRI (External organisation)
Advisor
22/3/2021
SULSA (University Administered) (External organisation)
Advisor
1/1/2020
UKRI Medical Research Council (External organisation)
Advisor
1/6/2019
Moninder Bhogal
Host
1/5/2019

More professional activities

Projects

Honours student project: How does S-acylation stabilise SARS-CoV-2 proteins?
Salaun, Christine (Co-investigator) Chamberlain, Luke (Principal Investigator)
24-Jan-2022 - 09-Jan-2022
S-Acylation of transmembrane proteins in the early secretory pathway
Chamberlain, Luke (Principal Investigator)
01-Jan-2022 - 30-Jan-2025
Targeting The ZDHHC9-Gcp16 Interaction As A Novel Therapeutic Strategy In Cancer And Neurological Disorders
Chamberlain, Luke (Principal Investigator) Tomkinson, Nick (Co-investigator)
01-Jan-2021 - 30-Jan-2025
SPRINT: A SuPer-Resolution time-resolved ImagiNg and specTroscopy facility for rapid biomolecular analysis
Li, David (Principal Investigator) Chamberlain, Luke (Co-investigator) Chen, Yu (Co-investigator) Cunningham, Margaret Rose (Co-investigator) Gould, Gwyn (Co-investigator) Hoskisson, Paul (Co-investigator) McConnell, Gail (Co-investigator) Rattray, Zahra (Co-investigator) Van de Linde, Sebastian (Co-investigator)
01-Jan-2021 - 28-Jan-2023
GlasBioPhys: An integrated facility for the analysis of biomolecular interactions (19ALERT Mid-range equipment initiative)
Burley, Glenn (Principal Investigator) Chamberlain, Luke (Co-investigator) Faulds, Karen (Co-investigator) Hoskisson, Paul (Co-investigator)
11-Jan-2020 - 09-Jan-2021
Role of S-acylation in viral biology
Salaun, Christine (Researcher) Chamberlain, Luke (Principal Investigator)
01-Jan-2020

More projects

Address

Strathclyde Institute of Pharmacy and Biomedical Sciences
Hamnett Wing

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