Blood clotting occurs in response to blood vessel damage. This requires the specific recruitment of platelets (specialised blood cells) to the site of injury as one of the first (of many) events that prevents bleeding. This process is highly dependent upon a protein known as von Willebrand factor (VWF) that circulates in blood. The ability of VWF to perform this task is regulated by an enzyme that is also present in the blood, ADAMTS13, and that, under very single substrate specific circumstances, cleaves VWF into smaller forms that are less capable of recruiting platelets. Clinically, deficiency in VWF is the most common inherited bleeding disorder, whereas people with ADAMTS13 deficiency suffer from a life-threatening thrombotic disorder with a ~90% mortality rate. More subtle differences in the blood levels/function of VWF and ADAMTS13 are also important determinants of an individual's risk of bleeding and thrombosis, and also influence the likelihood of both heart attack and stroke. ADAMTS13 is a very highly specific proteolytic enzyme that cleaves only one protein (VWF) and does so at just a single site, and even then, only under very specific conditions of blood flow. ADAMTS13 is made up of multiple domains. The metalloprotease domain of this enzyme contains the active site that cleaves VWF, whereas the other variably contribute to the binding of ADAMTS13 to VWF. Despite this knowledge, how ADAMTS13 recognises and cleaves VWF so specifically remains unclear. To understand this at a molecular level, we will ascertain the structure of different domains fragments of ADAMTS13, both in free forms and in stabilising complexes with specific antibody fragments that can aid in determining structures. In addition, we will also elucidate the structure of ADAMTS13 fragments whilst bound to the corresponding fragments of VWF. We will characterise the binding and cleavage of these VWF fragments by ADAMTS13 and also explore the influence of calcium binding to this process. The information from this project will provide important insights into how ADAMTS13 functions at a molecular level its unique single substrate specific cleavage of VWF. This data will provide the opportunity to rationally engineer ADAMTS13 to improve its efficacy as a therapeutic agent, for which it is currently under development as a more specific clotbuster for the treatment of thrombotic disease.

The worldwide transition from the use of oil-based to more sustainable feedstocks for plastics is underway. This transition is due to dwindling oil stocks and a realisation that current levels of the use of this resource is no longer sustainable. More sustainable sources for materials use exist in the form of cellulose from plants. This material is a very versatile polymer and is in fact the most utilised material worldwide. For the last 20+ years I have been researching the structure-property relationships of cellulose and am ideally placed to play a key role in the transition to renewable materials. Nature makes use of cellulose to good effect. Being intrinsically strong and stiff means that cellulose fibres, per weight, can compete mechanically with most synthetic alternatives such as glass. In nature's most prevalent natural composite - wood - cellulose forms the basis of its outstanding structural performance. All our attempts to replicate the composite performance of wood and plants have fallen short, and this fellowship seeks to address these issues, while also using the intrinsic properties of plant fibres and wood themselves. The proposed research aims to do this in the context of both natural and synthetic materials, adding functionality to the composites, while also addressing in a cross-cutting sense the sustainability credentials of the materials and structures proposed.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Modern manufacturing has been revolutionised by photonics. Lasers are central to this revolution, as they continue to transform the fast-changing manufacturing landscape. Photonics manufacturing represents an industry worth £10.5bn per annum to the UK economy, growing at about 8.5% annually and directly employing more than 70,000 people. UK Photonics exports are currently the 4th largest by value of any UK manufacturing sector, following automotive, aerospace and machinery exports. More importantly, UK Photonics exports more than 75% of its output relative to the UK manufacturing average of only 34%. Laser technology in particular underpins a number of leading UK industries in the aerospace, automotive, electronics, pharmaceuticals and healthcare engineering sectors. Over four decades, the Optoelectronics Research Centre at the University of Southampton has maintained a position at the forefront of photonics research. Its long and well-established track record in fibres, lasers, waveguides, devices, and optoelectronic materials has fostered innovation, enterprise, and cross-boundary multi-disciplinary activities. Advanced fibres and laser sub-systems, manufactured in Southampton by companies spun-out from the Optoelectronics Research Centre, are exported worldwide. Working closely with UK photonics industry, our interconnected and highly synergetic group will optimally combine different laser technologies into hybrid platforms for miniaturised, efficient, low-cost, agile and reconfigurable smart laser systems with software-driven performance. This is only possible because of the controllable, stable and robust, all-solid state nature of guided-wave lasers. A smart laser looks like its electronic equivalent - a single small sealed maintenance-free enclosure with a fully controlled output that is responsive to changes in the workpiece. The laser knows what material it is processing, how the process is developing and when it is finished. It is able to adapt to changes in the materials, their shape, reflectivity, thickness and orientation. This leads to new tools that enable innovative manufacturing processes that are critical in increasing competitiveness in important manufacturing sectors. Finally, the advanced laser technologies developed within this platform are expected to have a wider impact outside the manufacturing arena, in areas such as sensing, healthcare, and the medical sectors, as well as homeland security helping to establish an important laser sovereign capability.

Concerns are growing about how much melting occurs on the surface of the Greenland Ice Sheet (GrIS), and how much this melting will contribute to sea level rise (1). It seems that the amount of melting is accelerating and that the impact on sea level rise is over 1 mm each year (2). This information is of concern to governmental policy makers around the world because of the risk to viability of populated coastal and low-lying areas. There is currently a great scientific need to predict the amount of melting that will occur on the surface of the GrIS over the coming decades (3), since the uncertainties are high. The current models which are used to predict the amount of melting in a warmer climate rely heavily on determining the albedo, the ratio of how reflective the snow cover and the ice surface are to incoming solar energy. Surfaces which are whiter are said to have higher albedo, reflect more sunlight and melt less. Surfaces which are darker adsorb more sunlight and so melt more. Just how the albedo varies over time depends on a number of factors, including how wet the snow and ice is. One important factor that has been missed to date is bio-albedo. Each drop of water in wet snow and ice contains thousands of tiny microorganisms, mostly algae and cyanobacteria, which are pigmented - they have a built in sunblock - to protect them from sunlight. These algae and cyanobacteria have a large impact on the albedo, lowering it significantly. They also glue together dust particles that are swept out of the air by the falling snow. These dust particles also contain soot from industrial activity and forest fires, and so the mix of pigmented microbes and dark dust at the surface produces a darker ice sheet. We urgently need to know more about the factors that lead to and limit the growth of the pigmented microbes. Recent work by our group in the darkest zone of the ice sheet surface in the SW of Greenland shows that the darkest areas have the highest numbers of cells. Were these algae to grow equally well in other areas of the ice sheet surface, then the rate of melting of the whole ice sheet would increase very quickly. A major concern is that there will be more wet ice surfaces for these microorganisms to grow in, and for longer, during a period of climate warming, and so the microorganisms will grow in greater numbers and over a larger area, lowering the albedo and increasing the amount of melt that occurs each year. The nutrient - plant food - that the microorganisms need comes from the ice crystals and dust on the ice sheet surface, and there are fears that increased N levels in snow and ice may contribute to the growth of the microorganisms. This project aims to be the first to examine the growth and spread of the microorganisms in a warming climate, and to incorporate biological darkening into models that predict the future melting of the GrIS. References 1. Sasgen I and 8 others. Timing and origin of recent regional ice-mass loss in Greenland. Earth and Planetary Science Letters, 333-334, 293-303(2012). 2. Rignot, E., Velicogna, I., van den Broeke, M. R., Monaghan, A. & Lenaerts, J. Acceleration of the contribution of the Greenland and Antarctic ice sheets to sea level rise. Geophys. Res. Lett. 38, L05503, doi:10.1029/2011gl046583 (2011). 3. Milne, G. A., Gehrels, W. R., Hughes, C. W. & Tamisiea, M. E. Identifying the causes of sea-level change. Nature Geosci 2, 471-478 (2009).