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ScienceDirect Editorial overview: Mechanistic biology: Dynamic interactions in biology — sensing change Paula J Booth and Lynne Regan Current Opinion in Chemical Biology 2015, 29:viii–ix For a complete overview see the Issue Available online 18th November 2015 http://dx.doi.org/10.1016/j.cbpa.2015.11.003 1367-5931/# 2015 Elsevier Ltd. All rights reserved.

Paula J Booth and Lynne Regan Paula Booth is currently the Daniell Chair of Chemistry and Head of Department at King’s College, London, UK. Her research addresses the folding of integral membrane proteins, studying reaction mechanisms, regulation by membrane lipids and constructing biomembranes for Synthetic Biology applications. Paula studied Chemistry at Oxford University followed by a PhD at Imperial College, London. She ran her own lab at Oxford, Imperial College and Bristol where she was Professor in the School of Biochemistry. Lynne Regan is a professor of Chemistry and Molecular Biophysics and Biochemistry at Yale University. She was the president of the Protein Society for the 2013–2014 term. Her research centres on the relationships the relationships between structure, function, and stability in protein–protein and protein– DNA interactions.

The application of chemistry to elucidate changes and interactions in dynamic, complex biological systems has a long history, but because of new technological innovations it has perhaps never been so timely. Significant advances are being made by the application of new techniques that draw upon the combined power of analytical and physical chemistry. Additionally, novel methods are emerging that combine innovative chemical and molecular biology methods to perturb critical biomolecular interactions. A grand challenge of modern biology is to monitor, quantitatively model, and control interactions and reactions in live cells (see O’Green et al.). As researchers strive towards that goal, much can be elucidated by sophisticated biophysical methods in vitro, which are now successfully being applied to samples of ever increasing complexity. The articles in this issue cover methods to manipulate genetic mechanisms, protein interactions in solution in addition to novel strategies to probe and monitor active processes at membranes. Mechanistic biology is moving on from studies of individual proteins and complexes to tackle ever more complex biomachines, interactions between such machines and large bio-molecular assemblies. Observing biology in action is a challenge. There is an intricate interplay of events regulated by dynamic arrangements of proteins and biomolecules. This is exemplified in the highly orchestrated processes of biogenesis; ribosomes busy translating the genetic code are directing the correct folding and trafficking of proteins. The basic facets of the molecular machinery associated with this vital co-translation are conserved across life forms. The co-ordination of this process at membranes is especially important, and rather poorly understood in molecular detail. The review by Elveborg and Walter is an excellent overview of the latest developments in the control of the interaction between an actively translating ribosome and the translocation machinery at the membrane. These studies illustrate the advances in understanding of how complex biomolecular machines, co-operate and synchronise with each other. Bombardier and Munson discuss the tightly controlled processes of snare-mediated membrane fusion and exocytosis. These are dramatic events that require massive remodelling of membranes and huge topological changes. A combination of genetic, biochemical and biophysical approaches have begun to delineate the key steps and mechanisms by which these processes are controlled. The membrane theme is continued in the articles of Beedle and Garcia-Manyes together with that of Koc¸er, which both focus on the sensing of mechanical force and the importance of single molecule measurements. Beedle and Garcia-Manyes approach this from the point of view of the membrane lipid composition and overall membrane mechanical properties,

Current Opinion in Chemical Biology 2015, 29:viii–ix

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Editorial overview Booth and Regan ix

whilst Koc¸er addresses the detailed mechanism of an embedded mechanosenstive membrane channel. The latter demonstrates the exquisite detail that can be attained through engineering and perturbations of the protein itself to probe channel opening and sensing of changes in membrane tension. These complement prior electrophysiological measurements to measure ion flow. The approaches used to elucidate the chemical origin of membrane mechanics rely on single molecule force studies of natural membranes as well as synthetic ones of controlled lipid composition. These highly specific force probes also require the development of suitable biological samples. The ability of basic research to uncover unprecedented activities which can then be harnessed for myriad practical applications is well illustrated by the article by Reddington and Howarth. Typical proteins are synthesized as a linear chain of amino acids, with no branching.

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Certain proteins on the surface of bio-film forming bacteria, however, form covalent isopeptide cross-links between the side-chains of lysine and glutamic acid residues. By separating such a protein into two halves, researchers have shown that the branching can be coopted in a variety of ways, including stabilizing proteins, to create higher-order assemblies and materials and to create branched, multi-arm displays of proteins as novel vaccines. This collection of reviews gives a taste of the exciting developments taking place. Mechanistic Biology is an area where we can expect considerable change in the future. We are only at the beginning of realising the power of sophisticated, near atomic, resolution physical science approaches to elucidate the dynamics of complex biological systems. Advances in this area will continue to rely on skilful and innovative studies in in vitro and in vivo systems in parallel.

Current Opinion in Chemical Biology 2015, 29:viii–ix

Editorial overview: Mechanistic biology: Dynamic interactions in biology - sensing change.

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