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The process of crystal nucleation from solution requires, as its initial stage, separation of solute and solvent molecules and simultaneous formation of molecular clusters in order to create a new, nano scale, phase which can subsequently grow to become a crystal. Elucidating the fundamental physics and chemistry that govern the structure of this nucleation transition state remains one of the truly unresolved 'grand challenges' of the physical sciences. Individual nucleation events are localised in space but rather infrequent on the time-scale of a molecular vibration making both experimental detection and molecular modelling of the process difficult. In addition to this, available experimental techniques provide data averaged over both time and space so that extracting insights into the nucleation process may only be achieved through a combination of experiment and modelling. We propose a novel approach to this problem in which we scrutinise the crystallisation of two related molecular systems in hitherto unprecedented depth, building on established state-of-the-art experimental and computational techniques, but combining these, for the first time, with in situ synchrotron radiation (SR) X-ray scattering and spectroscopy methodologies capable of probing long range and local electronic and geometric structure at molecular resolution. Our hypothesis is that, by utilising appropriate experimental conditions, applying these state of the art time resolved scattering and spectroscopic techniques and building cluster models that are consistent with macroscopic features of the systems studied (crystal morphology, polymorphic form, solution chemistry, crystal growth rates), we can deduce a structural model of a nucleation event from the change in averaged solution structure as a function of increasing solution supersaturation and time. We thus expect incisive structural information for every step of the nucleation process: measured molecular scale properties can be used to confront computational predictions at molecular, supra-molecular and solid-state levels, so that the structural and size parameters for the nucleation pathway are revealed. A step change in our understanding of this area of science is thus expected.

The general public is exposed through the media to countless claims concerning the efficacy of counselling and various forms of psychotherapy for the treatment of depression and other mental health and personal problems. Health service providers are under increasing pressure to increase the availability of counselling and psychotherapy. There is clearly a need to design and implement controlled clinical trials to test whether these therapies work. It is equally clear that we need to develop and implement research projects that can tell us how these therapies work, what are the sources in the variability in responses to therapy and how these might be manipulated so that the therapies can be refined and improved. Equally, if a particular form of therapy does not appear to be very effective, we can use the same sources of information to develop an improved version that might be.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Cardiovascular disease is the leading cause of death worldwide. Vascular smooth muscle cells (VSMC) are implicated in the pathogenesis of several types of vascular diseases, such as aneurysm, atherosclerosis, vascular calcification and congenital vascular disease. VSMCs in different blood vessels are heterogeneous, behave differently in healthy and diseased states and derive from different embryonic progenitors. This project will use the latest technologies (single cell RNA-seq, single cell ATAC-seq, spatial transcriptomics) to resolve VSMC subpopulations in the developing human embryo, trace their lineage history and uncover the regulatory programs responsible for their differentiation. The discovery and characterization of disease-relevant transcriptional and chromatin signatures in VSMC subpopulations will help clarifying the basis of human cardiovascular pathology, enable diagnostic solutions for cardiovascular disease and facilitate reverse engineering of human tissues for regenerative purposes.