A new journal of quantitative biosciences from nano to macro
John McCarthy started his research career studying the biochemistry and biophysics of electron transport-dependent ATP synthesis. In subsequent years as a postdoc and then group leader in Germany, he worked on prokaryotic posttranscriptional control, with a major focus on the diverse set of mechanisms controlling expression of the atp operon in Escherichia coli. Expression of this operon was found to be regulated by a combination of controls exerted at the levels of translation initiation, translational coupling and mRNA decay, thus enabling correct assembly of a membrane-associated H+-ATPase with the highly complex stoichiometry a3b3g1d1e1a1b2c10. Novel principles of posttranscriptional control were elucidated and also applied to various challenges in biotechnology. In the early nineties, the research focus of the McCarthy group switched to posttranscriptional control in eukaryotic systems. Working with both Saccharomyces cerevisiae and mammalian cells, the main themes addressed were the 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 eukaryotic initiation factors (eIFs) and of translational regulators, and the structure and function of the yeast ribosome. Highlights have included the discovery of uORF-mediated control of mRNA decay in yeast (including the yeast YAP genes), quantitative characterization of the influence of phosphorylation on the mechanism of translational regulation via 4E-binding proteins, reports on structurally and functionally novel cap-binding proteins in Schizosaccharomyces pombe, single molecule analysis of the forces and dynamics of ribosomal scanning, a groundbreaking 3D reconstruction of the eukaryotic 43S complex (together with Gilbert/Stuart, Oxford), and elucidation of the molecular principles underlying ribosome recruitment to the mRNA 5'cap via the eIF4F complex (together with Gross/Wagner, Harvard). The McCarthy group has also been active in developing new biophysical and biochemical tools, including SPR methods for studying RNA-protein interactions, and single molecule imaging and manipulation methods for studying the eukaryotic ribosome. Currently, the McCarthy group utilises methods from biophysics, molecular biology and systems biology to study posttranscriptional control in yeast, and has initiated a number of synthetic biology projects in yeast and E.coli. The above work has been published in more than 100 papers in international peer-reviewed journals and has resulted in 5 patents. He has edited three books and a journal issue (on biophysical techniques in the journal Methods). John McCarthy has directed or co-directed a series of international conferences (8) and advanced lecture courses (4) on various aspects of the Posttranscriptional Control of Gene Expression and Quantitative Bioscience (funded by NATO Scientific Affairs Division, EMBO, FEBS and industry). While in Germany, he led joint projects with fourteen of the leading biotechnology and pharmaceutical companies in Europe. Since returning to the UK, he has collaborated with Merck and Pfizer, and currently has collaborative projects with Tepnel (Warrington) on developing immobilised ribosome-based assay systems and with Akubio (Cambridge) on applications of biosensor technology. John McCarthy is Chair of the Chemical Biology Interface Forum (and Fellow) of the Royal Society of Chemistry, chairs Royal Society Grants Committee Board F, and is on the John Innes Centre Governing Council. He was Chair of the Department of Biomolecular Sciences at UMIST (1998-2000). Since 1998, he has led a new initiative to promote research at the interface between bioscience and the physical sciences, engineering and mathematics: the Manchester Interdisciplinary Biocentre (MIB). He has been Director of the MIB since 2004. The MIB building (£38Mio) opened in 2006, and will house up to 75 research groups. John was the recipient of a Wolfson-Royal Society Merit Award in 2002, and has recently been awarded a BBSRC Professorial Fellowship.
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