Stony Brook University

East Africa (EA) has one of the world's fastest growing populations, with maxima around water-bodies and rapid urbanisation. Climate change is adding to existing problems increasing vulnerability of the poorest. HyCRISTAL is driven by EA priorities. EA communities rely on rainfall for food via agriculture. EA's inland lakes are rain-fed and provide water, power and fisheries. For EA's growing cities, climate impacts on water resources will affect water supply & treatment. HyCRISTAL will therefore operate in both urban & rural contexts. Change in water availability will be critical for climate-change impacts in EA, but projections are highly uncertain for rain, lakes, rivers and groundwater, and for extremes. EA "Long-Rains" are observed to be decreasing; while models tend to predict an increase (the "EA Climate paradox") although predictions are not consistent. This uncertainty provides a fundamental limit on the utility of climate information to inform policy. HyCRISTAL will therefore make best use of current projections to quantify uncertainty in user-relevant quantities and provide ground-breaking research to understand and reduce the uncertainty that currently limits decision making. HyCRISTAL will work with users to deliver world-leading climate research quantifying uncertainty from natural variability, uncertainty from climate forcings including those previously unassessed, and uncertainty in response to these forcings; including uncertainties from key processes such as convection and land-atmopshere coupling that are misrepresented in global models. Research will deliver new understanding of the mechanisms that drive the uncertainty in projections. HyCRISTAL will use this information to understand trends, when climate-change signals will emerge and provide a process-based expert judgement on projections. Working with policy makers, inter-disciplinary research (hydrology, economics, engineering, social science, ecology and decision-making) will quantify risks for rural & urban livelihoods, quantify climate impacts and provide the necessary tools to use climate information for decision making. HyCRISTAL will work with partners to co-produce research for decision-making on a 5-40 year timescale, demonstrated in 2 main pilots for urban water and policies to enable adaptive climate-smart rural livelihoods. These cover two of three "areas of need" from the African Ministerial Council on Environment's Comprehensive Framework of African Climate Change Programmes. HyCRISTAL has already engaged 12 partners from across EA. HyCRISTAL's Advisory Board will provide a mechanism for further growing stakeholder engagement. HyCRISTAL will work with the FCFA global & regional projects and CCKE, sharing methods, tools, user needs, expertise & communication. Uniquely, HyCRISTAL will capitalise on the new LVB-HyNEWS, an African-led consortium, governed by the East African Community, the Lake Victoria Basin Commission and National Meteorological and Hydrological agencies, with the African Ministerial Conference on Meteorology as an observer. HyCRISTAL will build EA capacity directly via collaboration (11 of 25 HyCRISTAL Co-Is are African, with 9 full-time in Africa), including data collection and via targeted workshops and teaching. HyCRISTAL will deliver evidence of impact, with new and deep climate science insights that will far outlast its duration. It will support decisions for climate-resilient infrastructure and livelihoods through application of new understanding in its pilots, with common methodological and infrastructure lessons to promote policy and enable transformational change for impact-at-scale. Using a combination of user-led and science-based management tools, HyCRISTAL will ensure the latest physical science, engineering and social-science yield maximum impacts. HyCRISTAL will deliver outstanding outputs across FCFA's aims; synergies with LVB-HyNEWS will add to these and ensure longevity beyond HyCRISTAL.

Oxides are an important class of solid state material with a wide range of properties which are key to understanding the fundamental way in which electrons behave in solids, and which are central to many important technologies. This proposal aims to investigate a less well known class of solid state compound: the oxysulfides, which contain both oxide and sulfide ions and which often adopt layered structures with well-defined oxide-rich portions intergrown with sulfide-rich portions. The investigation of the way in which electrons and ions behave in each layer and the interaction between the two types of layer is expected to yield a range of properties complementary to those of the oxides and may yield compounds with application in new technologies.New oxysulfide compounds identified in recent years in the PI's group will be measured using a range of experimental techniques such as neutron powder diffraction, in-situ X-ray powder diffraction, magnetometry and electrical conductivity measurements. Solid state nuclear magnetic resonance (NMR) spectroscopy will also form an important part of the programme and will be carried out in collaboration with the group of Prof. Clare Grey at SUNY Stony Brook. The results of all these measurements will be correlated with each other, with theoretical calculations carried out on these materials, and with results reported on other, related materials. The aims are to answer fundamental questions about the electronic properties of the materials and to investigate the mobilities of lithium, and copper ions in these compounds. The compounds will be compared with analogous oxides and sulfides. The synthetic part of the programme will extend the range of synthetic techniques available in the PI's group for the synthesis of materials to include electrochemical methods which will offer greater compositional control over some of the products These investigations will specifically focus on understanding the transition from the insulating state to the conducting state in solids and the correlation of such electronic changes with changes in the crystal structure of the compounds. The ionic mobilities will be correlated with the behaviour of materials which are important as electrodes and possible electrolytes in rechargeable lithium ion battery technologies. Furthermore the ionic mobilities will be correlated with the electronic and structural changes.The collaboration between the PI's group, which has expertise in synthesis, structural characterisation and physical property measurements, and Prof. Grey's group, which is world-leading in solid state NMR spectroscopy is an important component of the project. The relationship between the two groups will be strengthened by regular exchange of personnel for training purposes and the exchange of ideas.

The oxygen we breathe and the food we eat ultimately derive from photosynthesis, the conversion of the sun's rays into useful chemical energy by plants and bacteria. However, we can have too much sunshine. Just as humans can suffer from skin cancer due to harmful UV rays in the sun, so plants and bacteria can be damaged by too much sunlight. As a result of these conflicting demands it is essential for a wide range of living organisms to have some means of sensing light levels. That plants have such tools is obvious to anyone who has ever grown cress on a windowsill and seen it turn towards the light. What we are principally concerned with in this project is precisely how plants and bacteria sense light, and whether this process can be exploited in human applications. In this proposal we focus on one particularly useful family of photosensor proteins, the LOV (Light-Oxygen-Voltage) domains. Over the past twenty years many proteins have been discovered which detect light. The LOV domain proteins are part of a much larger group called the flavoproteins. 'Flavo-' means yellow indicating that these proteins are colored and thus have the ability to absorb light energy. In the photoactive flavoproteins, which includes the LOV domains, this energy is converted it into some useful structure change in the protein. This then stimulates further changes in associated proteins which ultimately gives rise to a specific biological response. This complex chain of events in known to be important in: determining when flowers open; making leaves turn towards the sun; causing bacteria to swim away from harmful sunlight; controlling circadian rhythms, etc. In a few cases the structures of these LOV domain proteins have been determined, and other experiments have shown what secondary proteins (or DNA) they are complexed with, which informs us about their function. However, very little is known about the mechanism of operation of photoactive flavoproteins, beyond the fact that the proteins binds a flavin molecule which absorbs blue light. The question at the heart of our research is how is the event of light absorption can be converted into a specific structure change which acts as a signal to initiate other processes in living cells. In this work we will use some of the most sophisticated methods of laser spectroscopy to record what happens to the proteins after they have absorbed light. It is through the application of such advanced physical methods to living systems that we can begin to understand (and even control) the chemistry of life. In this case we will stimulate the protein response with a short pulse of blue light (less than 100 million billionths of a second long) and use another short pulse of light to take ultrafast 'snapshots' of the structural changes as they happen. We will follow these structure changes right from the time of excitation all the way through to formation of the final signalling state. By thus observing protein function in real time we will obtain new insights into the mechanism of how plants 'see' light. We will then use some tricks of protein chemistry to test, probe and manipulate these structure changes. Our interest in these proteins is not simply curiosity as to how they work. Recently scientists have artificially incorporated light-activated proteins into various cells and then used light to trigger a particular response. The most famous example is the use of light to activate the firing of neurons in the brains of mice, but as other light-activated proteins (such as LOV domains) become better understood it will become possible to stimulate a variety of new phenomena. The ability to stimulate a specific process in a living cell with both time and space resolution will represent a powerful new tool for scientists trying to understand cellular functions, and will inform a variety of research in health sciences.

A detailed understanding of the innate workings of the cell is imperative for our prospects of making new advances in the treatment of infections and disease. How the cells of our body respond to stresses ranging from cancer to the common cold is all highly sought knowledge. To help reveal this information we intend to design a range of small chemical compounds which can get into the cells and shut down the function(s) of specific proteins in order to observe the effects on the cell and reveal the role of specific proteins in cell maintenance. This can be achieved by using chemicals which mimic the ones the proteins normally work with and use them to distract the protein from doing its proper job. We want to mimic sugar nucleotides (sugar-NDPs).Sugar-NDPs are the building blocks used by a class of intracellular biocatalytic proteins know as glycosyltransferases (GTs). GTs biosynthesise oligosaccharides and glycoproteins which are central players in cellular function and maintenance. Sugar-NDPs carry some 'fat-repelling' negative charge which stops them from escaping the cells' watery innards through the greasy cell membrane, but also prevents the delivery of sugar-NDP mimics into the cell. The ability to prepare uncharged sugar-NDP mimetics which can ultimately diffuse into cells and perturb the function of specific GTs would be extremely desirable. We will develop synthetic chemical methods that will facilitate the preparation of such sugar-NDP-like compounds by replacing the negatively charged component of the sugar-NDP (ie. the pyrophosphate group) with a sugar molecule. The sugar should be able to mimic the missing pyrophosphate component and also help to make the sugar-NDP mimic more greasy. This will increase its chances of getting into get into the cell across the greasy cell membrane to do the job at hand. Current methods for synthesising such molecules can be particularly challenging and time consuming. However we will design a selection of simple chemical building blocks that be chemically 'clipped' together in different combinations so that it will be possible to prepare a range of uncharged sugar-NDP-like structures in a less labour intensive manner.

A detailed understanding of the innate workings of the cell is imperative for our prospects of making new advances in the treatment of infections and disease. How the cells of our body respond to stresses ranging from cancer to the common cold is all highly sought knowledge. To help reveal this information we intend to design a range of small chemical compounds which can get into the cells and shut down the function(s) of specific proteins in order to observe the effects on the cell and reveal the role of specific proteins in cell maintenance. This can be achieved by using chemicals which mimic the ones the proteins normally work with and use them to distract the protein from doing its proper job. We want to mimic sugar nucleotides (sugar-NDPs).Sugar-NDPs are the building blocks used by a class of intracellular biocatalytic proteins know as glycosyltransferases (GTs). GTs biosynthesise oligosaccharides and glycoproteins which are central players in cellular function and maintenance. Sugar-NDPs carry some 'fat-repelling' negative charge which stops them from escaping the cells' watery innards through the greasy cell membrane, but also prevents the delivery of sugar-NDP mimics into the cell. The ability to prepare uncharged sugar-NDP mimetics which can ultimately diffuse into cells and perturb the function of specific GTs would be extremely desirable. We will develop synthetic chemical methods that will facilitate the preparation of such sugar-NDP-like compounds by replacing the negatively charged component of the sugar-NDP (ie. the pyrophosphate group) with a sugar molecule. The sugar should be able to mimic the missing pyrophosphate component and also help to make the sugar-NDP mimic more greasy. This will increase its chances of getting into get into the cell across the greasy cell membrane to do the job at hand. Current methods for synthesising such molecules can be particularly challenging and time consuming. However we will design a selection of simple chemical building blocks that be chemically 'clipped' together in different combinations so that it will be possible to prepare a range of uncharged sugar-NDP-like structures in a less labour intensive manner.