Prof Ivan Gout

My research has been focused for many years on the regulation of cell growth and metabolism in health and disease. In the course of these studies, we discovered several key signalling and metabolic enzymes, including S6K2, mTORb and CoA synthase. We have made significant contributions to understanding the role of these enzymes in signal transduction and the regulation of cellular metabolism.

Building on these findings, we have uncovered a novel post-translational modification, termed protein CoAlation, and antioxidant function of coenzyme A (CoA). Our studies have revealed that protein CoAlation is a widespread and reversible post-translational modification induced by oxidative or metabolic stress. It has been detected in single-cell and multicellular organisms, including bacteria, yeast, algae, amoeba, flies and mammals.

We have developed a range of new research tools and methodologies, which have been instrumental for uncovering protein CoAlation and antioxidant function of CoA. These include: a) unique anti-CoA mAbs which work efficiently in various immunological assays (anti-CoA antibody is not commercially available); b) in vitro protein CoAlation and deCoAlation assays; c) a reliable strategy for the identification of CoAlated proteins by LC-MS/MS. To date, using the developed methodology, we have identified more than 1000 CoA-modified proteins under various experimental conditions in prokaryotic and eukaryotic cells.

These advances put us into a unique position of being able to readily detect protein CoAlation in cellular response to oxidative and metabolic stress, to identify CoAlated proteins, and to study molecular mechanisms underlying the CoAlation/deCoAlation cycle. 

The following projects are currently under study:

1. Investigating the molecular mechanisms of protein deCoAlation;

2. Defining the identity and function of eukaryotic CoA disulphide reductase;

3. Regulation of peroxiredoxins by covalent CoA modification in cellular response to oxidative or metabolic stress;

4. CoAlome analysis of bacterial spores;

5. Of particular interest is understanding the role of protein CoAlation and antioxidant function of CoA in human pathologies, associated with oxidative stress, such as cancer and neurodegeneration.

Our research is leading us towards exciting new ideas aimed at the development of novel diagnostic and therapeutic approaches for cancer and neurodegeneration, which we pursue.