Dimethylsulfoxide (DMSO) is a chemical with a wide range of applications. It is a widely used solvent, for instance in pharmaceutical applications, and a waste product of the paper milling industry. It also occurs naturally in a range of fruits, like raspberries, and vegetables. However, DMSO is also a compound that is part of the natural sulphur cycle. Sulphur is an essential element for all life, and in its organic form is a component of all proteins such as the amino acids cysteine and methionine. DMSO is an organic sulphur compound found everywhere in our oceans, and is produced by a number of natural biological and chemical processes. DMSO is important because it is both a source and a sink for a climate-cooling gas called dimethyl sulfide (DMS). DMS is a component of the smell of the seaside. Around 300 million tons of DMS are made each year by marine microorganisms. Some of this DMS is released into the atmosphere above the oceans, where it reacts in air to compounds that seed clouds, which is suggested influences weather and climate. When it rains, sulphur compounds are deposited back into the soils of our continents. However the majority of the DMS formed in the oceans is thought not to be released to the atmosphere, but rather to be converted to DMSO, and thus stays in seawater. However what happens to this DMSO largely remains a mystery, but it has been suggested that it can be converted back to DMS, and thus be a source for climatically relevant sulphur emissions to the atmosphere. What we do know is that DMSO is commonly the most abundant organic sulphur compound in the oceans, and represents a major pool of the essential life elements sulphur and carbon. The research to be carried out in this proposal is focused on firstly finding out what happens to DMSO in seawater. We have some preliminary evidence, found using radiolabelled DMSO as a tracer, that it is degraded by microorganisms who both incorporate its carbon into their biomass for growth purposes, and degrade it to carbon dioxide. However we also think that perhaps other microbes could transfer DMSO back to DMS, and even use its sulphur as an essential element. Therefore in this proposal we have designed a series of different tracer experiments to find out which processes occur in our seas, how important they are and how fast they happen. We will also put names to the microbes using DMSO, and find out which metabolic pathways are involved. We will study these microbial DMSO transformations in the English Channel at a station called L4. This station is sampled weekly as part of the Western Channel Observatory which is coordinated by Plymouth Marine Laboratory. This is a long-standing time series site for which data on phytoplankton diversity, abundance, temperature, nutrient dynamics and bacterial diversity are also measured and will be made freely available to this project (http://www.westernchannelobservatory.org.uk). Given the important role of DMSO and its related compound DMS, identifying the populations and pathways of DMSO removal from seawater will provide key information that will improve our future understanding of the complex sulphur cycle and how it influences our climate.

The dietary vitamin B3, which encompasses nicotinamide, nicotinic acid and nicotinamide riboside, is precursor to the coenzyme nicotinamide adenine dinucleotide (NAD+), its phosphorylated parent (NADP+) and their respective reduced forms (NADH and NADPH). Once converted intracellularly to NAD(P)+, it is used as a co-substrate in two types of intracellular modifications, which control numerous essential signalling events (adenosine diphosphate ribosylation and deacetylation), and is a cofactor for over 400 redox enzymes, thus controlling metabolism. Critically, the NAD(P)(H)-cofactor family can promote mitochondrial dysfunction and cellular impairment if present in sub-optimal intracellular concentrations. Vitamin B3, and other B-vitamins such as thiamine (vitamin B1), riboflavin (vitamin B2) and pyridoxine (vitamin B6) are extracted in their coenzyme forms from food stuff. During digestion, the coenzymes are catabolised to the free circulating vitamins, which are then passively or actively transported across membranes, and salvaged intracellularly to their respective cofactors. Mammals are entirely reliant on a dietary source of vitamin B1 and heavily dependent on the dietary supply of vitamin B3, B2, and B6. Of note, acute deficiencies in vitamin B1 and vitamin B3 effect identical organs, with identical outcomes if left untreated: dementia and death. Conditions such as diabetes and obesity, alcoholism, high fat diet and conditions where therapy impacts nutrition can compromise suitable absorption of these vitamins. The bulk of intracellular NAD+ is regenerated via the effective salvage of nicotinic acid and nicotinamide (vitamin B3), while de novo NAD+ is obtained from tryptophan. Crucially, these salvage and de novo pathways depend on the functional forms of vitamin B1, B2 and B6 to generate NAD+ via a phosphoriboside pyrophosphate intermediate. Nicotinamide Riboside (NR) is the only form of vitamin B3 from which NAD+ can be generated in a vitamin B1, B2 and B6 independent manner and even though NR is a minor component of vitamin B3, the salvage pathway using NR for the production of NAD+ is expressed in most eukaryotes. While major strides have been made in the field of NAD+ biology and NAD+ metabolism, the role of this later pathway and the importance of the interplay between the bioavailability of vitamin B1, B2 and B6 and the pool of NAD(P)(H)-cofactors remain poorly explored. Using our synthetic expertise in nucleotide and stable isotope labelling chemistry, we will generate isotopically labelled vitamin B1 and B3 derivatives. These entities will be used to determine the profile of the vitamin B3 metabolome quantified by mass spectroscopy, under vitamin B1, B2 and B6 depletion conditions, in genetically engineered yeast strains and mammalian (murine and human) hepatocytes. In mammalian cells, these metabolic profiles will be correlated to mitochondrial functions. With this information, we will be able to prioritise the mechanisms cells use to best maintain the NAD(P)(H) pool in time of shortage of vitamin B1, B2 or B6. We predict that the pathway, by which NR is converted to NAD+, provides the means to rapidly yet transiently elevate mitochondrial and cytosolic NAD(P)(H) levels to kick start mitochondrial functions. If demonstrated, this knowledge will help identify new, physiologically relevant, vitamin-B combinations that could better restore mitochondrial function through enhanced bioavailability, in cells and organs where metabolism has been compromised by imbalanced micronutrition. This knowledge will be particularly important in terms of understanding the impacts of a global or partial vitamin B deficiency and vitamin B supplementation on organ functions in relation to malnutrition and over-nutrition.

The polar regions are experiencing the most rapid climate change observed on Earth: temperatures are rising in some regions of the Arctic and Antarctic at more than double the global average rate, there has been a dramatic increase in extreme warming events, and there are concerns about the impact of ice melt on global systems. Marine ecosystems are already responding to - and amplifying - environmental change, with important implications for carbon burial and important natural resources such as fisheries. One important type of microalgae, which form the basis of these polar ecosystems and provide an important conduit for carbon flow from the surface to the seafloor, are diatoms. Diatoms build their microscopic shells from silica, and so dissolved silicon (DSi) is a critical nutrient for their growth. As such, we need a better understanding of how climate-sensitive processes within polar environments impact the nearshore, shelf and open ocean exchange of silicon cycling, and their consequences for regional and global systems. The cycling of silicon behaves very differently in the two polar regions. There is increasing evidence that - in many Arctic regions - how and how much DSi reaches the surface ocean essentially sets the degree to which diatoms can grow and fix carbon. Around Antarctica, nutrient-rich nearshore shelf waters exchange with the open ocean and feed downstream via the Antarctic Circumpolar Current into the Southern Ocean, which - in turn - supplies nutrients to the global ocean. The sources of this critical nutrient, DSi, to the polar oceans, especially from glacial weathering, and the physical mixing and upwelling processes that supply DSi to surface waters are likely to change into the future, with significant impacts on regional biological productivity and further afield. SiCLING will investigate links between silicon and metal cycling within glacial sediments in Arctic and Antarctic fjords, resulting in a step-change in our understanding of silicon mobility and bioavailability in fjords, high-latitude nutrient balance, and the flow of nutrients into the polar coastal ocean and beyond. Our recent work has shown that glaciers are a substantial source of both dissolved silicon (DSi) and reactive particles of silica, termed ASi. However, the processes by which DSi and ASi escape glaciated fjords are not understood; these processes have profound implications for the supply of DSi to coastal and open ocean ecosystems in the polar regions, and ultimately how this system will respond and change in the future. We have shown that within fjords, nearer the glaciers, DSi within has a unique geochemical and isotopic fingerprint - and this fingerprint appears to be the same wherever we look: in the Arctic, Antarctic and in mid-latitude glaciated mountain regions like Chilean Patagonia. Given the extent and the nature of this signal, we propose that there is an important and ubiquitous - but yet unknown - mechanism that controls the release of DSi into fjords and then into the coastal ocean, acting as an effective trap of this important nutrient. We propose that this mechanism is not entirely biological, but relates to the interactions between silicon and another important element for life: iron. Iron is also released in large quantities from glacial weathering, and the iron released is capable of mopping up significant quantities of DSi. This mechanism is likely to be climate sensitive (because of the glacial meltwater source and temperature/salinity effects), and understanding the underlying processes will be crucial for predicting future change especially in the context of accelerating polar warming and land-ice melting. SiCLING will be the first project to focus specifically on these previously overlooked links between dynamic silicon and iron cycling in the polar regions, incorporating cutting-edge analysis of field and laboratory samples and advanced geochemical modelling.