Studies investigating the effects of nanoplastics (NPs) on aquatic organisms used concentrations between 2 to 7 order-of-magnitudes higher than those predicted in the open ocean in order to be able to track NPs. These studies divided the community between those sounding the alarm due to the observed ecotoxicological effects, and those predicting that NP concentrations in the environment are far below any threshold-effect. In reality most experiments were inadequately designed, and thus the results unsatisfying. Fit-to-purpose experimental designs have been hindered by a lack of appropriate NP models, tracking methods, and monitoring strategies for environmentally realistic concentrations. Using 14C-labelled NPs and conventional nuclear techniques, we have recently modelled that scallops, chronically exposed (over a year) to environmentally realistic NP concentrations (15 ug/L) might accumulate and reach NPs concentrations in body tissue where effects have been observed by those sounding the alarm. Astonishingly, this suggests that NPs might already be beyond threshold-effects in organisms and harming the marine biota. Here, we will deliver an innovative approach that will overcome the analytical limitations for detecting, mapping and quantifying NPs in realistic environmental settings. By combining 14C-labelling of NPs with the ultimate sensitivity of Accelerator Mass Spectrometry (AMS), METABOLISM will allow to investigate whether NPs in the oceans are already beyond "threshold-effect" concentrations in tissues. METABOLISM will: i) provide representative intrinsically radiolabelled NP models; ii) perform chronic NP exposures with a model organism (i.e. mussels) at environmentally realistic NP concentrations (ppt-levels); iii) develop the combustion AMS to generate toxicokinetic data; iv) explore the LA-AMS to produce spatially-resolve 14C measurement to quantify tissue distribution of NPs. The approach proposed here is essential and will produce unique, valuable and fundamental knowledge on the combined long-term accumulation of NPs in aquatic environments. This is critical for developing appropriate management strategies regarding plastic litter. If successful, METABOLISM will indeed support policy makers in improving environmental risk assessments of NPs and other contaminants of emerging concerns (CEC). It is envisioned that the approach proposed herein will enable a step-change in the research on CECs and will allow the study of many different aspects of their fates (e.g., transformation, fragmentation, biomineralization, biodistribution). METABOLISM chooses a highly innovative approach to address its research questions. It combines radiochemistry and unlock the power of the AMS to resolve important environmental questions. It will establish 14C-labelled NPs as a gold standard for performing realistic laboratory-based studies. It is fundamental research that will have a critical impact beyond its overall goal. The research proposed will, for instance, have a huge impact on the use of 14C as low-level tracer in biomedical studies (i.e. micro-dosing), where appropriate methods are often missing. The approach proposed is unique and will allow to perform ground-breaking science that goes beyond the state-of-the-art. METABOLISM builds an inter-disciplinary research team that integrates the relevant expertise in environmental analytical chemistry, radiochemistry and physics.

With age, we gradually accumulate both environmentally and intrinsically generated defects at different levels in our bodies: from errors in DNA (mutations), proteins (aggregates), organelles (mitochondrial dysfunction) to cells (cancer) and organs (heart failure). Ageing is the largest risk factor for the majority of human diseases in the Western world, including progressive diseases such as Alzheimer's and Parkinson's, diseases like cancer that show variable rates of onset, and catastrophic systems failures such as heart-attack and stroke. While the study of specific ageing-related disease processes has long been a major focus of biomedical and biological research, there is a growing realisation of the importance of analyzing the normal ageing process itself as an essential part of the problem, and of exploring ways to slow or reverse its effects. Ageing is a multi-factorial problem that can be seen as an inevitable feature of the ravages of time and the harmful environments in which organisms live. Recent discoveries, however, demonstrate that ageing can be modified in dramatic ways by relatively simple interventions. For example, single gene mutations and dietary restriction can delay ageing and provide a universal improvement in health late in the life of laboratory animals. Moreover, the pathways involved in ageing are conserved in evolution, and genetic variants in their components are associated with differences in lifespan in humans. A central challenge of ageing research, however, remains to tease out a comprehensive and unified picture of the genetic factors and mechanisms determining longevity. We plan to utilize fission yeast as a model organism to advance our understanding of complex processes with fundamental importance for ageing. Remarkably, many of these processes are now known to be similar from yeast to human. Yeast cells enter a quiescent, non-dividing state under limiting nutrients, and the lifespan in this state depends on both genetic and environmental factors. Such quiescent yeast cells provide a valuable system to analyze basic processes affecting ageing and longevity. We will analyze how the global regulation of genes and proteins is modified during ageing, and how any changes might affect longevity. We will also exploit a collection of all viable gene knock-out mutants to systematically identify those genes that lead to longer or shorter lifespan. We will further examine how lifespan varies among wild yeast strains from different geographical locations, and whether this variation goes with changes in gene expression. Finally, we will integrate these complementary global data sets and follow-up the most promising findings to uncover particular roles of specific genetic factors in cellular ageing and longevity. Importantly, this research will provide a valuable platform to understand the genetic factors involved in ageing in humans, to eventually develop interventions that slow ageing and thus prevent or delay the numerous age-associated diseases.

Density Functional Theory is an atomic scale tool which can be used to learn about the structure and behaviour of substances, especially when atoms or molecules react with one another. For instance, it has been used to tell us about how the structure of water changes when it becomes acid or alkali. It is true to say that it has revolutionised our understanding in many aspects of science, and one of the originators (Walter Kohn) was awarded the Nobel Prize (in 1998) for developing the underlying theory which is at the heart of DFT computer simulation software. Since the first implementation of DFT, several flavours of DFT have been developed that have generally increase accuracy of this method, allowing scientists to calculate energies for chemical reactions with amazing accuracy. The usefulness of this method is increased when computer processors can be utilised in parallel to divide up the calculation into small sub-calculations. Currently Intel are marketing their Duo core processors for desktop and notebook computers where the computer is able to split the computational burden over two processors. The same principle is used on national supercomputers, where over 1000 processors can be used to make very demanding calculations (that would take 1000 years on one processor) into a far more manageable task, taking one year on 1000 processors, assuming the program was perfectly efficient. In reality, it is very difficult to obtain such efficient parallelism / special tricks need to be used to use the computer processor performance. This application seeks funding to develop a popular new piece of software that it can run far more efficiently on the new national supercomputer.Once the develpoment has taken place, we will look in detail at the structure and nanoscopic defects in ice. Understanding the structure and behaviour of microscopic imperfections in the ice structure will lead us to better understand how it conducts but more generally, how these defects influence the stability of ice. The latter is becoming ever more topical and important as we seek to understand how ice melts in order to better estimate the influence of temperature on glacial ice sheet.

Following on from a successful project studentship this is a proposal to continue the development of a birefringence imaging microscope incorporating a tilting stage. The birefringence is an important and sensitive measure of optical anisotropy in a sample and in conventional microscopy it is usually only observed in projection onto a microscope slide. The addition of a tilting stage enables in principle information to be obtained out of the plane and hence to give full three-dimensional data. The resulting system will help towards automatic identification of crystalline materials and, of especial interest, the determination of texture in specimens, such as in petrological sections and in mixed phase crystals. As such this topic is interdisciplinary in nature, spanning crystallography, materials science, earth sciences and chemistry.

Some of the most spectacular data in the recent history of earth science have been derived from the drilling of the polar ice caps. Foremost amongst these is the revelation that the atmospheric CO2 content was about one-third lower (roughly 80ppmV) during the Last Glacial Maximum than during the warmer period of the past 10 thousand years. Thus, it is widely believed that changes in atmospheric CO2 strongly amplified glacial-interglacial climate change. Although a clear explanation has yet to emerge for the observed CO2 decline during glacials and rise during interglacials, mass balance arguments clearly point to the ocean exchange as the primary modulator of the CO2 changes on these time scales. Recent studies have pointed to the Southern Ocean due to the tight coupling between carbon dioxide levels and climate in the southern hemisphere high latitudes. One prevailing model involving the SO envisions that at the end of the last glacial cycle (deglacial) climate reorganisation, the reduction in sea ice cover and strengthening wind fields may have stirred up deep ocean waters rich in carbon and nutrients to the surface releasing CO2 that has been stored in the deep ocean during the glacial period. However, this model presents a paradox. In the modern SO, the physical release of CO2 is roughly compensated by the uptake of carbon by algae during photosynthesis at the sea surface utilising the nutrients that accompany CO2 in the resurfacing deep waters. Therefore for the CO2 release model to work conditions in SO should have been unfavourable for the biological uptake allowing globally significant CO2 efflux to occur. In the proposal we hypothesize that one potential factor that could have constrained biological CO2 uptake in the SO is the dearth of Fe during algal growth. The substantial decline in dust inputs (important source of Fe) during the deglacial recorded in Anatrctic ice cores lends support to this idea. Therefore, we propose to investigate the role of productivity on CO2 efflux from the SO during the last deglaciation by investigating the nature and magnitude of marine productivity, relative macronutrient utilisation (nitrate and silicic acid), micronutrient (Fe & Zn) bio-availability and in a carefully selected set of marine sediment cores covering this period. We propose to apply state-of-art geochemical and isotopic tools recently developed including silicon and nitrogen isotopes as proxies for macronutrient utilisation and diatom-bound trace metals as tracers of Fe and Zn biological availability in combination with more conventional proxies of productivity and dust inputs. By doing so, we propose to address a fundamental and lingering question in Earth System Science- that is "What are the controls on glacial-interglacial CO2 change?"