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Biological molecules interact through multiple weak bonds, which define the specificity and the affinity of the interaction. One would expect that the total strength of this interaction would equal the sum of all the contributing weak bonds in isolation. However this is not the case, and interactions are often much weaker or stronger than expected (known as cooperativity). This often corresponds with the function of the molecules. The majority of functional biological molecules are proteins, the large macromolecules that are encoded by DNA. Proteins that bind to rare nutrients (biotin or iron) or highly unstable structures (rate-defining intermediates of chemical reactions) bind more tightly than expected, whereas other proteins bind and release abundant molecules quickly (for example the reactants and products of biochemical reactions, like glucose or lactate), but must still bind specifically. This is most striking in enzymes, which speed up biochemical reactions by binding to rate-defining intermediates of chemical reactions (transition states). They must also bind to the reactants and products of the reactions, which are very similar in chemistry to the transition state, but must be bound much more weakly. The focus of this study is how enzymes combine these two modes of binding in their reaction cycles, and how they use their intrinsic flexibility to do so. We wish to test whether structural tightening provides a mechanism of achieving this discrimination. NMR allows the measurement of the properties of individual atoms within large molecules, but there is a size limit to the size of molecules that can be studied. Over time this size limit is increasing as technology improves and is now at a stage where large enzymes like phosphoglycerate kinase (PGK) can be studied. This project will use this technology to determine the contributions that different atoms within this enzyme make to the binding of the transition state of the reaction it catalyses, using stable chemicals that resemble it (called transition state analogues). The conclusions should be broadly applicable to other enzymes. An understanding of this process is vital to the design inhibitors of enzymes for use as therapeutic agents (drugs) and to technologies that use enzymes out of their biological context, for example bioremediation. It will also help the theoretical understanding of how important biological molecules work.

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.

No abstract available.

Nature writing in Britain is probably as popular as it has ever been, but it remains critically undervalued. It is also frequently misunderstood. One source of misunderstanding is the view that nature writing supports the myth of stable order --social, moral, ecological-- while another is that it performs a consolatory aesthetics designed primarily to restore its readers to the natural world. These views overlook the significant conflicts that have been embedded within British nature writing ever since it emerged as a modern form in the late eighteenth century. Many of these conflicts are coeval with modernity. How can we know 'nature', and is it really possible to describe it? To what extent is 'nature' a projection of our own individual and collective (national) imaginings? How much can we appreciate it when there is so little of it left? The product of a collaboration between four leading scholars in the field, this project will be the first full-length study of its kind of modern British nature writing, beginning in 1789 with Gilbert White's seminal study, The Natural History of Selborne, and ending in 2014 with Helen Macdonald's prize-winning memoir, H is for Hawk. Between the two lies the jagged history of a genre that emerges under the sign of a triple crisis: the crisis of the environment; the crisis of representation; and the crisis of modernity itself. Emphasis will be placed on non-fictional prose, not because it is the 'truest' form of nature writing, but because it brings out one of the genre's most fundamental tensions: between the desire to set up a mimetic relation to the natural world and the awareness of the impossibility of doing so, for 'nature' is always other to what we imagine it to be, even if we are a part of it ourselves. Methods will be drawn from environmental history and philosophy as well as literary criticism, working together in the spirit of the environmental humanities, which seek to show how text- and discourse-based perspectives on culture, ethics, and history can work together with more empirical forms of scientific research, e.g. those connected with ecology, to produce enhanced understandings of changing human interactions with the natural world. The project will offer fresh readings of some of the classic texts of British nature writing, interpreting these in the light of current understandings of fractured subjectivity, post-equilibrium ecology, and the tangled relationship between humans and other animals in what some recent critical theorists have taken to calling an increasingly 'post-human', even a definitively 'post-natural', world. These understandings are seen by some as underlying the so-called 'new nature writing' that has emerged in Britain over roughly the last three decades; but this writing is not as 'new' as it appears, and one of the tasks of the project will be to confirm the historical grounding of contemporary debates. Only by seeing nature writing historically, it will be argued, can it be defended against the peremptory view that it practises a naive realism, or the hasty conclusion that it adopts a largely devotional attitude to the natural world. On the contrary, nature writing is a highly self-reflexive form: well aware of its own limited understandings, finely attuned to the inadequacy of its own language, and keenly conscious of the illusory nature of its attempts to achieve a three-way reconciliation between self, text, and world. Whether nature writing has potential to transform the world it describes is moot, but nature writing is not an escapist form and the project -- which will combine academic work with a variety of public engagement activities involving co-participants of all backgrounds and ages -- will show how it engages productively with a modern world that is both inhabited by possibly irremediable crisis and haunted by possibly irretrievable loss.

Early pregnancy is a major cause of mortality amongst young African women. Early Marriage is a major cause of pregnancy. Young women in conservative Islamic communities are particularly vulnerable to early marriage. New research has emerged about the potential impact of participatory community interventions and cash transfer intervention in delaying marriage by increasing uptake of education. However, these interventions have not yet been tried in a conservative Islamic setting. This study will build on new knowledge about the effectiveness of cash transfer and community interventions to delay marriage to develop an intervention to delay marriage in conservative Islamic communities in Eastern Sudan.

Radiotherapy uses radiation to kill tumour cells and is given to about 40% of cancer patients as part of their treatment. There is a maximum radiation dose that can be given to a patient because radiation also damages the healthy tissues that surround the tumour. This radiation dose may thus not be sufficient to kill the tumour. The aim of our research is to improve radiotherapy by making tumour cells more sensitive to radiation. We have identified particular proteins that are important for a tumour cell to survive radiation. We showed that when these proteins are inhibited, the radiation kills tumour cells more effectively without affecting healthy cells. The outcome of radiotherapy is also influenced by the tumour environment. Tumours often have core areas with low oxygen levels. As the absence of oxygen greatly decreases the efficacy of radiation, these regions are much more resistant to radiotherapy. One way to improve the availability of oxygen in these areas is to reduce the amount of oxygen that is consumed by cancer cells throughout the tumour. We have identified an anti-malarial drug that can do exactly that and showed that it improves radiotherapy in mice. We are now conducting a clinical trial to test whether this drug improves oxygen levels in patients’ tumours.

Twenty percent of the Scottish population live within 1 km from the coast and in the future is expected at a higher risk of erosion and flooding. The Scottish Government have assessed the erosion vulnerability of the Scottish Coasts through the National Coastal Change Assessment project - NCCA. The assessment employed the Coastal Erosion Susceptibility Model (CESM), a parametric-based approach estimating the shoreline changes based on topography, rockhead elevation, proximity, wave exposure, coastal defence, and historic sediment supply. The produced national scale map is showing the historical shoreline evolution at 147 sites, also mentioning the assets in threat. However, the future projections are only locating the sites that can experience erosion, not necessarily indicate that the sites currently undergo or will be eroded. My doctorate research aims to address this gap, providing a more realistic shoreline change projection using the process-based model. Compare to the CESM, it requires more computational effort but benefiting the decision-maker by visualizing the mechanism of climate changes and human interventions in impacting the coast. The sea states, such as sea-level rise, wave climates, and storms are being altered by climate change. Extreme events are expected to become more frequent in the future and therefore result in a bigger risk of coastal erosion. Moreover, the coastal defence in some cases does not stop the erosion, rather it relocates the threat to other areas. The process-based model will be used to understand this phenomenon. The Delft3D (open-source), XBeach (open-source), and UNIBEST are the core tools in this research, well-known for coastal modelling develop by Deltares. These suites have been tested in the Netherlands (Sand Engine) and the Korean Coast, performing well in replicating the shoreline change both in long-term and storms condition. In this research, some critical coasts with distinctive characteristics will be taken as a study case. Investigation on these areas not only will elucidate the coastal processes at the specific sites, but also act as a rule of thumb for other sites with a similar environment. This series of research is designed to be completed in three to four years. The first year is allocated for examining the research question, building a collaboration with the forefront researcher, and collecting the relevant data. The second and third years focus on validating the model and proceeding to project the impact of climate changes and human interventions. The thesis and examination are to be finished in the early of the fourth year. This research will illustrate how resilient the Scottish Coasts in the changing climate and the more frequent storms. Also, the most effective adaptation measures will be proposed for each area of interest. The advantages and disadvantages of the process and parametric-based approach will be underlined, opening up the possibility of coupling in formulating the strategic shoreline management plans.

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.

Building on our prior work where we prepared uranium-carbon double bonds that are heavily stabilised by two phosphorano groups and then evolved this to a less stabilised silyl-phosphino combination, we aim to target genuine actinide-carbon bonds that are not stabilised at all, other than by the actinide (uranium and/or thorium). Thence, this would then secure one of the long-standing goals in synthetic actinide chemistry to provide a type of complex called an actinide-alkylidene, pure variants of which have thus far only been prepared in cryogenic (5 K) matrix isolation spectroscopic experiments. The objectives are therefore to: (1) extend the range of silyl-phosphino systems to include oxidation states of uranium other than +4; (2) prepare thorium analogues; (3) with the knowledge from (1) and (2) systematically decrease the stabilisation at carbon by exchanging the silyl for alkyl and phosphino for aryl in different combinations; (4) if successful, extend the range of oxidation states for uranium and probe the inherent reactivity and electronic structure of these compounds. This project will involve organic and inorganic synthesis methods es, structural, spectroscopic, and magnetic characterisation techniques, and computational techniques. The student will be trained in handling radiochemicals, highly sensitive compounds, and developing novel synthetic methodologies to construct the actinide-carbon double bonds which are anticipated to be novel compared to established d-block analogues.

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