Professor of Molecular Systems Biology,

Director of WISB

Email: John.McCarthy@warwick.ac.uk 

Phone: 024 765 73431

Office: MB15

Research Clusters

Quantitative, Systems & Engineering Biology

Warwick Centres and GRPs

Warwick Integrative Synthetic Biology Centre

Vacancies and Opportunities

For PhD and postdoctoral opportunities, and interest in potential collaborations, please contact me at the above email address.

Research Interests

Living cells contain genes whose informational content needs to be converted into cellular components that form structures and enable biochemical reactions to take place. This process is called gene expression and it is vital to all known life. Gene expression comprises two main synthetic steps, called transcription and translation. In transcription, the information in the DNA sequences of the genes is converted into equivalent sequences in so-called messenger RNA (mRNA) molecules. In translation, the mRNA molecules are "read" by a large molecular structure called the ribosome, which uses the information to dictate the synthesis of proteins. The proteins synthesised in this way have to fold into a number of types of three-dimensional structure in order to become active. The McCarthy group studies the structure, function and regulation of the cellular machineries that perform the translation part of gene expression. We have also embarked on a new scientific venture to engineer innovative control devices based on cellular translational components, with a view to creating novel, faster-acting control systems that can be used both in academic research and industrial processes. One area of application is in optimizing the performance of metabolic pathways that generate high-value chemicals for use in medicine, agriculture and the environment.

We have known for some time that processes like gene expression and signalling in biology do not proceed at constant rates at the molecular level. There are considerable fluctuations (noise) in the functioning of their molecular processes. It is now thought that these fluctuations actually play important roles in evolution, gene regulation, stress responses, ageing and other processes in biology. In other words, noise is not just a damaging, randomizing influence in biology. We are particularly interested in the mechanisms that cells use to harness the beneficial properties of gene expression noise.

Research: Technical Summary

The McCarthy group has an extensive track record in the molecular systems biology of posttranscriptional gene expression, studying the structural and behavioural features of key molecular components of the cellular machineries involved in mRNA translation and degradation. Working with bacterial systems, Saccharomyces cerevisiae and mammalian cells, themes addressed have included mechanisms underlying posttranscriptional control by structural elements (including uORFs, protein-binding sites and aptamer-binding sites) in the untranslated regions of mRNAs, the mechanism of selenocysteine incorporation, the structure and function of the eukaryotic translation machinery and of translational regulators. We have been active in developing new biophysical, biochemical and systems biology tools, including SPR methods for studying RNA-protein and protein-protein interactions, fluorescence techniques applicable to the eukaryotic ribosome, single molecule imaging/manipulation methods, in vivo rate control measurements, and single-cell studies (using fluorescence microscopy, flow cytometry/cell-sorting and microfluidics) of gene expression stochasticity. Current projects focus on: gene expression noise and its roles in evolution and ageing, high-throughput strategies for optimising metabolic pathways, bioengineering of next-generation posttranscriptional devices and circuitry, whereby all our work incorporates both cutting-edge experimental strategies and (ODE-based) modelling. McCarthy publications >130; h-index = 56.

Publications

For a full list of publications, see WRAP