This fellowship will be used to establish a multidisciplinary team working at the interface of chemistry, biology and protein engineering at the University of York, UK. The overarching goal of my group's research will be to develop novel approaches for biopolymer synthesis, design and discovery. In the process, we want to unravel the mechanisms that control and modulate the behavior of enzymes and proteins. The methodologies developed and insights gained through this proposal will inform the synthesis strategies for a new generation of therapeutics and biomaterials. Chemical synthesis remains the mainstay for the production of drugs, including the modern, next generation biologics composed of peptides, proteins, DNA, RNA, carbohydrates and their conjugates. Biomolecular conjugates have also found use as nanomaterials, drug delivery vehicles and components of biocomputers. Traditional chemical methods of synthesis require harsh conditions such as high temperature, non-aqueous solvents and non-physiological pH - parameters that are often incompatible with the manufacture of biomolecules. It is therefore imperative that alternative, sustainable strategies are explored. Enzymes present a biocompatible mode of synthesis that is starting to be exploited for the manufacture of biomolecular drugs. In this proposal, my research group will focus on adapting natural enzymes to perform the synthesis of a commonly used hybrid biomolecule - peptide-oligonucleotide conjugate. The knowledge gained will be used to further expand the existing repertoire of biologics and biomaterials.

Copepod species of the genus Calanus (Calanus hereafter) are rice grain-sized crustaceans, distant relatives of crabs and lobsters, that occur throughout the Arctic Ocean consuming enormous quantities of microscopic algae (phytoplankton). These tiny animals represent the primary food source for many Arctic fish, seabirds and whales. During early spring they gorge on extensive seasonal blooms of diatoms, fat-rich phytoplankton that proliferate both beneath the sea ice and in the open ocean. This allows Calanus to rapidly obtain sufficient fat to survive during the many months of food scarcity during the Arctic winter. Diatoms also produce one of the main marine omega-3 polyunsaturated fatty acids that Calanus require to successfully survive and reproduce in the frozen Arctic waters. Calanus seasonally migrate into deeper waters to save energy and reduce their losses to predation in an overwintering process called diapause that is fuelled entirely by carbon-rich fat (lipids). This vertical 'lipid pump' transfers vast quantities of carbon into the ocean's interior and ultimately represents the draw-down of atmospheric carbon dioxide (CO2), an important process within the global carbon cycle. Continued global warming throughout the 21st century is expected to exert a strong influence on the timing, magnitude and spatial distribution of diatom productivity in the Arctic Ocean. Little is known about how Calanus will respond to these changes, making it difficult to understand how the wider Arctic ecosystem and its biogeochemistry will be affected by climate change. The overarching goal of this proposal is to develop a predictive understanding of how Calanus in the Arctic will be affected by future climate change. We will achieve this goal through five main areas of research: We will synthesise past datasets of Calanus in the Arctic alongside satellite-derived data on primary production. This undertaking will examine whether smaller, more temperate species have been increasingly colonising of Arctic. Furthermore, it will consider how the timing of life-cycle events may have changed over past decades and between different Arctic regions. The resulting data will be used to validate modelling efforts. We will conduct field based experiments to examine how climate-driven changes in the quantity and omega-3 content of phytoplankton will affect crucial features of the Calanus life-cycle, including reproduction and lipid storage for diapause. Cutting-edge techniques will investigate how and why Calanus use stored fats to reproduce in the absence of food. The new understanding gained will be used to produce numerical models of Calanus' life cycle for future forecasting. The research programme will develop life-cycle models of Calanus and simulate present day distribution patterns, the timing of life-cycle events, and the quantities of stored lipid (body condition), over large areas of the Arctic. These projections will be compared to historical data. We will investigate how the omega-3 fatty acid content of Calanus is affected by the food environment and in turn dictates patterns of their diapause- and reproductive success. Reproductive strategies differ between the different species of Calanus and this approach provides a powerful means by which to predict how each species will be impacted, allowing us to identify the winners and losers under various scenarios of future environmental changes. The project synthesis will draw upon previous all elements of the proposal to generate new numerical models of Calanus and how the food environment influences their reproductive strategy and hence capacity for survival in a changing Arctic Ocean. This will allow us to explore how the productivity and biogeochemistry of the Arctic Ocean will change in the future. These models will be interfaced with the UK's Earth System Model that directly feeds into international efforts to understand global feedbacks to climate change.

Ocean acidification due to the dissolution of anthropogenic CO2, and the effects of cumulative stressors (including acidification, pollution, warming, and anoxia) are among the top priorities for ocean research, requiring accurate and consistent measurements across the globe to monitor and understand present effects, and modelling to evaluate future scenarios and methods of remediation. The work of observational scientists and modellers is linked by the need for an accurate knowledge of the chemical speciation of the inorganic carbonate system, pH, and nutrient and contaminate trace metals, in both natural waters and the reference materials and solutions used for instrument calibration. Chemical speciation is defined as the distribution of a chemical element between different molecular and ionic forms in seawater, and determines its reactivity and bioavailability. Speciation depends on the value of the relevant thermodynamic equilibrium constant, and on the activities of each of the dissolved ions and molecules. These are complex functions of temperature, pressure, and salinity (or, more generally, solution composition), and cannot be predicted from theory. Many of the important reactions in seawater involve acid-base equilibria, which introduces pH as an additional variable. Despite the importance of chemical speciation, the available calculation tools are often only simple empirical equations that yield equilibrium constants for reactions as functions of salinity and temperature. Such equations cannot be used for many important natural waters whose composition differs from that of normal seawater (e.g., polar brines, estuaries, pore-waters, enclosed seas, and paleo-oceans). Furthermore, human-driven changes in seawater pH and carbonate chemistry in shelf seas and estuaries are complicated by the effects of eutrophication, upwelling, the dissolved solutes contained in river water, and changes in metal toxicity accompanying pH change. Consequently, despite the best efforts of physical chemists over the last several decades, there is not yet the ability to calculate the equilibria controlling the chemical factors impacting shellfish and a broader range of marine fauna in the brackish/mesohaline environments typical of many estuaries and coasts. We will create a step change in the capability of marine scientists to measure, interpret, and predict chemical speciation and pH in natural waters of varying composition by creating a speciation model based upon the Pitzer equations for the calculation of solute and water activities. The approach has a long track record of success in geochemistry. The equations are based upon the concept that interactions between pairs and triplets of dissolved solute species control activities. The values of the parameters for these interactions are determined from a wide range of measurements of solution properties. Work in this project will include measuring activities and heat capacities, and using recent literature data, to improve and test the model; the computer coding and validation of the model and the development of methods to quantify the relationship between uncertainties in model-predicted speciation and those in the underlying measurements; and engagement with oceanographers internationally to help design practical speciation modelling tools and associated guidance for specific applications. The completed model will enable the activities and speciation of all seawater components to be calculated within a unified framework that, (i) includes the major and trace elements in seawater and its mixtures with freshwaters, (ii) includes other saline environments of differing composition, and (iii) encompasses the buffers that are used to calibrate pH and other instruments, and. Our results will this advance the quantitative understanding of chemical speciation - from ocean measurements to ecosystem models - for an expanded range of natural water bodies and marine environments.

Permanent offshore structures form artificial reefs which provide attachment and settlement sites for marine organisms. In the UK, some of the oldest platforms have been in the water for over 40 years and have considerable colonisation of marine organisms. Marine Growth organisms generally include seaweeds, soft corals and mussels in the areas where light penetrates(photic zone) as well as anemones, hydroids and cold-water corals on the deeper sections of the platforms. One of the first marine growth studies published was on the Montrose platform back in 1982; and significant discoveries have been made during offshore installation marine growth assessments since then, such as the first discovery of the CITES Listed Lophelia pertusa coral growing on offshore platforms during the decommissioning of the Brent Spar storage buoy, the with results subsequently being published in Nature in 1999. L. pertusa as since been recorded on the majority of northern North Sea platforms - and therefore their presence on the structures may be contributing to the connectivity of the protect reefs in the UK and Norway. Marine growth causes issues for the oil and gas industry (operators) by adding additional weight to the structure which may cause damage and impair visual inspection of important equipment, both in routine and decommissioning scenarios. New areas of interest have also developed around platform marine growth, including the potential for marine invasive species, potential "stepping stone" habitats, artificial reefs for conservation (e.g. de-facto MPAs) or fish using the structures for food and shelter. In areas of the Gulf of Mexico, a "rigs-to-reef programme", (the conversion of offshore platforms into designated artificial reefs) is underway. However, in Europe, particularly in the North East Atlantic OSPAR region, there is a requirement to remove all offshore infrastructures from the seabed (although derogations may be granted). As part of the decommissioning plan, an operator may be required to assess the extent of marine growth on a platform to determine the additional weight added to the platform (for structure removal) or for potential organic waste disposal and especially if species of conservation importance (e.g. Lophelia and Sabellaria) are present. This project will use a pre-devolved method (CoralNet) to analysis images of marine growth on offshore structures. The method will allow for more images to be analysed, compared to traditional assessment methodology and will allow for a more consistent approach, potentially providing for a good long-term monitoring tool. In addition, finding new and innovative monitoring methods, is not only about collecting data in the field, but also about how the data should be analysed, with this project will contribute.

The South Asian summer monsoon (June-September) provides 80% of the annual rainfall for over one billion people, many of whom depend on monsoon rains for subsistence agriculture and freshwater. It is critical to forecast accurately not only the seasonal rainfall, but also rainfall variations within the summer. Sub-seasonal "active" and "break" phases can last weeks, resulting in floods and droughts across broad areas of South Asia. Air-sea interactions are key to understanding and predicting monsoon behaviour. Ocean surface temperatures in the Bay of Bengal, east of India, remain very warm (above 28 Celsius) throughout the summer. Evaporation from the Bay provides moisture and energy to monsoon depressions that form over the Bay and bring substantial rain to India. It is not understood how the Bay remains warm despite losing energy to these systems. Ocean temperature and salinity variations across the Bay are known to drive changes in rainfall over the Bay and surrounding land, but it is not clear how these arise or how they are maintained. This is particularly true for east-west variations in the southern Bay, a focus of this project. Although air-sea interactions are important to the monsoon, weather predictions are made with models of only the atmosphere. There is potential to improve monsoon forecasts by including well-represented air-sea interactions in models. The Bay of Bengal Boundary Layer Experiment (BoBBLE) proposes an observational campaign for the southern Bay, during the established monsoon (mid-June to mid-July). BoBBLE will deploy two ships, six ocean gliders and eight floats to collect an unprecedented range of oceanic and air-sea flux observations. The ships will occupy locations in the southwest and southeast Bay, as well as tracing east-west and north-south paths between those locations, measuring ocean temperature, salinity and currents. Two gliders (automated underwater vehicles) will accompany each ship, with two others between the ships, diving to 500 metres every 2 hours to measure temperature, salinity and currents. Diurnal variations in air-sea fluxes and ocean temperatures may affect the development of weather systems. A novel configuration of the gliders will allow computations of horizontal transports of heat and salt. The floats (automated submersibles) will be deployed in the Bay to measure the ocean to 2000 metres every 5 days. They will remain in the Bay after BoBBLE, enhancing the observing network. Ships and gliders will also measure ocean chlorophyll, which absorb sunlight and alter near-surface ocean temperature, influencing air-sea interactions. BoBBLE scientists will analyse these observations, along with routine datasets, to understand the evolution of conditions in the Bay and how they influence the atmosphere. Particular emphasis will be placed on estimating the uncertainty in existing datasets of air-sea fluxes by validating them against available observations. The best-performing datasets will be used to improve estimates of air-sea exchanges and their variability on daily to decadal timescales, to calculate budgets of heat and freshwater fluxes in the Indian Ocean and the Bay, and to validate model simulations. A hierarchy of model simulations will reveal how conditions in the Bay are maintained and how air-sea interactions influence the monsoon. Simulations with an ocean model, forced by and validated against BoBBLE observations, will isolate the roles of air-sea fluxes (including the diurnal cycle), chlorophyll and horizontal transports in maintaining and recharging ocean structure after each weather system passage. Retrospective forecasts of the BoBBLE period with atmosphere-only and atmosphere-ocean coupled models will demonstrate how air-sea interactions influence monsoon rainfall predictions. Multi-decadal simulations will evaluate how air-sea interactions and coupled-model systematic errors influence daily-to-seasonal monsoon variability