For nearly six decades, chemotaxis - a ubiquitous biological behaviour enabling the movement of a cell or organism toward or away from chemicals -has served as a paradigmatic model for the study of cellular sensory signal transduction and motile behavior. The relatively simple chemotaxis machinery of E. coli is the best understood signal transduction system and serves as a powerful tool for investigating the molecular mechanisms that proteins use to detect, process, and transmit signals. The sensory apparatus of E. coli cells is an ordered array of hundreds of basic core signalling units consisting of three essential components, the transmembrane chemoreceptors, the histidine kinase, and the adaptor protein. The core units further assemble into a two-dimensional lattice array which allows cells to amplify and integrate many varied and possibly conflicting signals to locate optimal growing conditions. To understand the underlying molecular mechanisms of chemosensory array assembly, activation and high cooperativity, it is essential to determine the precise interactions between the core signalling components in the context of the array. We propose to use a combination of cutting-edge cryoET structural methods and multi-scale molecular simulations, as well as in vivo functional assays, to investigate the structural and dynamical mechanisms underlying signal transduction and regulation. The research plan is divided into three aims: 1. Determine the structural basis of signal transduction and array cooperativity 2. Define conformational states and dynamics of the array 3. Obtain time-resolved structural snapshots of signalling pathway Our results will establish, in atomistic detail, the chemotaxis signalling pathway that is shared by diverse chemotactic species, including a wide-range of human and plant pathogens, thus impact on multiple disciplines, from antimicrobial drug development to understanding responses to hormones and neurotransmitters in eukaryotic cells.

Establishing the atomic arrangements in a molecule or a solid has been feasible for about 100 years by X-ray diffraction; most "pictures (stills)" of the structure of, for example, salt, insulin, haemoglobin and foot and mouse disease virus are based on this technique of scattering X-ray from crystals. For less ordered materials, like glasses and liquid solutions, partial, local structures can be derived from X-ray absorption spectroscopy. Both techniques require scattering off electrons and thus tell us about the atomic arrangements and some insight into electronic distributions. Chemical and light-induced changes are movements of electrons and atoms to new sites and so visualizing these evolutions by X-ray methods can provide chemical videos of reactions which have greater richness than before and after stills; this is the molecular parallel of picturing a galloping horse. Generally changes on the timescales of atomic motion occur between a 1/100 and 1 picosecond (1 ps = 1 millionth of a microsecond), and this has been monitored by changes in the uv and visible spectrum (colour). This provides little information about structure. Infra-red spectroscopy can be used for timescales greater than 1 ps, and is characteristic of functional groups within molecules. This proposal provides a means of approaching the detail of a molecular "still" through chemical changes. The Diamond Light Source is the brightest X-ray source in the UK, and provides the opportunity of studying structures on a timescale of 10s of picoseconds. This is fast enough to catch many excited states of fluorescent materials, and to observe the reactions of the most reactive of transient molecules. UV-visible and infrared spectroscopies will be monitored after changes induced by a laser pulse of about 1/5 of a picosecond. The fast laser spectroscopy will be combined with the rapidly developing technique of photocrystallography, where it is possible to obtain full 3-D solid-state structures of photoactivated species that have lifetimes in the nanosecond to millisecond range, so that it will be possible to make "molecular movies" showing how key chemical and biological processes occur. Thus, it will be possible to study important catalytic, sensor and non-linear materials across the time scales from picoseconds to milliseconds, to see how properties and functions develop over time. Sampling procedures for crystals, solutions and films will be developed and made available to other research groups. The whole approach should transform the way we think about chemical reactions. From such an approach there will be a fraction of problems for which even faster measurements would be fascinating. In recent years laser light in the X-ray region has become available in the USA and Japan (by X-ray free electron lasers, XFELs), and sources are being built in Europe (Germany and Switzerland). They provide an X-ray pulse of about 1/50 of a picosecond, faster than most molecular vibrations, and thus the X-ray movie of a chemical reaction is feasible. This proposal will provide a test-bed for researchers in the chemical sciences to develop their technique for visualizing their reactions. The facility will be based on the Harwell site adjacent to the equipment and expertise of the Diamond Light Source and Central Laser Facility, both of which are user facilities of the highest rank.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

See Je-S application of Oxford University (lead applicant, joint reference P1936803)

Cobalt is an essential element for modern world. Its use in metal alloys, rechargeable batteries, electronics and high-value chemicals make it critical for a low-carbon society. Cobalt has the largest global market value of any of the individual e-tech elements (US$2.1 billion in 2013). Cobalt is largely recovered as a by-product from the mining of other major metals and as a result, cobalt has not been the focus of study in ore-forming systems on its own. To address this knowledge gap we propose a systematic geological, geochemical and mineralogical approach to understanding the residence of cobalt in a range of important current and future ore minerals in diverse geological environments. A specific focus for this study are deposits forming in the Critical Zone of the Earth's crust where biological activity and weathering coincide and where cobalt is redistributed into forms where innovative bioleaching could change the way deposits are processed. Using new knowledge gained from the study of natural biological systems, advanced bioleaching techniques will be systematically applied to a range of deposits formed in the Critical Zone. Bioleaching also has great potential for reduced, sulfide-rich ores, particularly complex sulfide and often arsenic-rich ore-types where significant bioleaching has not yet been tested. This COG3 proposal builds on our catalyst grant which developed a multi-institute and multi-investigator consortium with internationally recognised expertise across the geosciences including geology, geochemistry, mineralogy, microbiology and bioprocessing based in leading UK academic institutes: Herrington (NHM), Schofield (NHM), Johnson (Bangor), Lloyd (Manchester), Pattrick (Manchester), Coker (Manchester), Roberts (Southampton), Gadd (Dundee), Glass (Exeter), Mosselmans (Diamond), Kaulich, (Diamond)and Kirk (Loughborough), with in-depth expertise on geology, geometallurgy and geomicrobiology applicable to developing recovery strategies for cobalt from natural deposits. This group is underpinned by the Partners including the major mining companies Glencore, FQML and KGHM; a mid-tier European-based mining company Oriel; a junior UK-based mining SME Brazilian Nickel, an internationally accredited commercial research laboratory RPC and finally the Cobalt Development Institute representing the cobalt industry throughout the supply chain. They have all pledged to engage with the project, some through direct involvement in research activities, some with financial support for research and training and others by facilitating access to natural deposits and datasets. Further support comes from research colleagues at CSIRO in Australia. Specific research will be delivered through a series of work packages which will address: 1) Geology and mineralogy of cobalt in natural systems; 2) Natural biogeochemistry of cobalt; 3) Bioprocessing of cobalt and development of new products; 4) Improving the cobalt supply chain through integrated studies and dialogue with stakeholders representing the supply chain. This research directly addresses the NERC Security of Supply of Mineral Resources (SoS Minerals) initiative Goals 1 & 2 with a fundamental aim to recognise the mineral residence and chemical cycle of cobalt (Goal 1) and provide geometallurgical information that will facilitate new opportunities for improvements to current recovery, minimising waste through geometallurgy; and thoroughly testing innovative, benign bioleach technologies for the extraction and downstream bioengineering of novel cobalt products (Goal 2). Through the collaboration of the PIs, Co-Pis, Partners and the development of PDRAs and PhDs, the program will produce high impact scientific publications for the international literature, highly significant public outreach and education on behalf of the NERC SoS programme and establish the UK COG3 consortium as a world leader in research into innovative cobalt recovery from natural mineral deposits.