We aim to create a research network between the UK and Sri Lanka to bring together archaeology and heritage academics and professionals, new researchers and graduate students, and representatives of NGOs, CSOs, and community groups, to develop dialogues that address challenges in the relevance and application of archaeology and heritage. This network will be a platform for building a new research project, allowing cross-disciplinary opportunities to co-create research that is relevant both to academics and to wider communities in Sri Lanka. Sri Lankan heritage is currently heavily oriented towards World Heritage sites of the early historic period, and a major challenge for the network is to explore ways to diversify this agenda. Of special interest to the network are heritages of the everyday and the more recent past, and finding approaches that value and privilege these in addition to the authorised heritage is a significant challenge. We believe there is space to offer different and multiple understandings of heritage in Sri Lanka, and want to use the research network to think through the value of working in the later historical period (i.e. 1200-1948) and exploring, recording and presenting heritages of everyday lives/people and places. This network is an ideal forum in which to discuss potential research themes within this framework, such as issues of contact and trade, the impact of movements and migrations, human-environment relationships and the ways these can be understood through material culture. As well as discussing these issues within an academic context, we will use the network to build contacts beyond academia and extend the dialogue on the relevance of archaeology and heritage to a wider community. We believe this is particularly important in areas such as the Northwest of Sri Lanka (which will be the spatial focus for the Network), where post-conflict communities are working to find a sense of place and belonging. Being able to network effectively with representatives from CSOs and NGOs that work locally means that the network will benefit from their ground-based knowledge and experience which will help shape approaches to understanding how archaeology and heritage could be important for communities, and support the creation of identity. This type of networking is also an excellent opportunity for non-academic groups to learn about what we do, and draw on it where useful to support and expand their own work. A good example of this from other contexts is work in London where psychologists have found that fine arts can be hugely helpful for recent refugees suffering trauma. The network will hold two major meetings. The first in the UK to enable Sri Lankan participants to visit and experience venues that focus on everyday heritage of the more recent past and to meet heritage practitioners, teachers and academics. The second in Sri Lanka will extend the dialogue in an open forum meeting in Colombo and also spend time in the Northwest meeting local groups, sharing experiences and exploring potential research questions. This network will include young researchers in discussions that have the potential to shape the ways in which archaeology and heritage are practiced in Sri Lanka. The Post Graduate Institute of Archaeological Research (PGIAR) is the only PG training institution in the discipline in Sri Lanka, and so has a pivotal role in training the university lecturers and practitioners of tomorrow. With the PGIAR as a partner in this network, their students will be able to join agenda-setting discussions with their primary partner, the Sri Lankan Department of Archaeological Survey, and help co-create an archaeology and heritage project that will put new principles and research aims into practice. Sri Lankan and UK researchers and students will also be able to participate in site visits and subsequent analyses in their respective countries, and network with senior academic and non-academic colleagues.

Project Highlights: Why individuals and species age so differently is an unanswered question in evolutionary biology. Diapause is an example of senescence plasticity, where the same genetics produces different ageing patterns in an organism. Using next-gen sequencing the project will measure DNA methylation across the genome of Nasonia and build the first insect epigenetic clock. Overview: This project will help understand why organisms age differently by establishing the effect of early life environments on epigenetic ageing in the model insect, Nasonia vitripennis. How individuals and species age so differently is one of the major unanswered questions in evolutionary biology with early life environments being a major predictor of lifespan. Ageing is a mechanistically complex process influenced by many environmental and genetic com- ponents. The effects of these components influence each other, making them difficult to investigate, especially in complex mammalian models. Therefore, a large body of ageing research is based on simple model invertebrate organisms. Advantages include easy and inexpensive to keep in a laboratory, short life span, genetic and molecular tools available, and a sequenced genome. However, current invertebrate ageing models (Drosophila and C. elegans) do not possess certain chemical marks (DNA methylation), an important part of how most organisms age. An epigenetic clock is a biochemical test based on measuring the accumulation of this DNA methylation. There is evidence that epigenetic clocks mirror true biological age and its associated morbidity and mortality better than chronological age in many species including us. The jewel wasp, Nasonia vitripennis, an emerging model, has a functional methylation system, making it an ideal species to investigate the epigenetics of ageing. We have established an epige- netic clock in this species. Early life effects on ageing have pervasive influence on the ecology and evolution of a range of species from fish to birds to humans. It would be useful to study a dramatic example, where a distinct early life environment lead to a dramatic switch in ageing strategy, a so-called senescence plasticity. An example of this is larval diapause in Nasonia where if the mother experiences autumn-like conditions, her larval offspring become dorminant over winter and then as adults live much longer than adult Nasonia who haven't overwintered. Methodology: This project combines whole genome bisulfite sequencing of Nasonia, machine learning, RNAi knockdowns of methylation enzymes and high-throughput behavioural analysis, to analyse chrono- logical and epigenetic ageing in diapaused and non-diapaused Nasonia.

Molecular imprinting involves making a binding pocket in a polymer which is chemically and shape specific for the target compound. These "smart plastics" offer robustness compared to biological molecular recognition elements such as antibodies and enzymes. They also have the ability to work in extreme environmental conditions. However, they can sometimes lack the necessary specificity/affinity. Aptamers are small pieces of DNA/RNA that have the ability to target proteins and small molecules and bind to them with high specificity and affinity. They are not toxic and are attractive alternatives to antibodies. They have been used primarily in research due to their susceptibility to enzymatic and chemical degradation, though this is slowly changing and they are becoming commercially relevant. The global aptamers market is projected to reach $2.4 billion by 2020, up from $1.1 billion in 2015. A 12-month proof-of-concept study, supported by the EPSRC and led by the PI (a molecular imprinting specialist), created novel hybrid materials made by incorporating aptamers into molecularly imprinted polymers (MIPs). In simple terms, the aptamer structure is modified to allow it to be directly incorporated into a polymer, so it will hold its shape while being protected from environmental conditions. Novel, high affinity and stable materials were created. These "aptaMIPs" demonstrated exceptional molecular recognition and offer significant improvements on both MIPs and aptamers in terms of stability, and specific target recognition, effectively maintaining the best properties of both classes of materials. This proposal seeks to explore the potential of aptaMIPs through a two year study into the core chemistry used to create these novel materials. We will build on the results of the pilot study and create useful, effective materials with high commercial potential. The research in this proposal will focus on: (i) Identifying the right linker chemistry; (ii) Developing polymerisable modifications for all four bases; (iii) Identifying how many linkers are needed; (iv) Identifying the best position for these linkers. An in-depth study on these four points will enable a full understanding of the key chemistry of how the aptamer incorporates itself into the polymer and, through this, allow us to understand what makes a good aptaMIP and why. Alongside these the synthetic strategies used will be analysed to ensure the creation of these hybrids is simple and effective. Two targets have been selected to study these chemistries. These differ in size and application: a protein and a bioactive drug, but both targets have significant commercial potential. Through these model systems we aim to demonstrate the validity and potential of aptaMIP materials. Alongside the PI, two project partners form the research team: The Watts group were collaborators on the pilot study and are based at the University of Massachusetts RNA Therapeutics Institute (a world leading school in novel aptamer synthesis). They will support the proposal through access to state-of-the-art synthesis equipment, combined with know-how in oligomer synthesis and application. Aptamer Group are a commercial aptamer development company based in York. Their expertise will benefit the project by providing the known oligomer sequences which will act as the basis for our studies and access to specialised instrumentation. The impact of the project will be supported by their detailed knowledge of the aptamer field and commercial outlook. The experience of the whole team will allow this interdisciplinary proposal, covering the fields of polymer, nucleic acid, protein and analytical chemistries to succeed. We will take aptaMIPs from the existing proof-of-concept stage and develop them, and their synthetic process, into viable competitors in artificial molecular recognition, ready for application in systems where their functionality can be exploited.

Using drugs that 'stick' proteins together, or 'molecular glues', is a potentially hugely powerful therapeutic strategy across a range of disease areas. However, molecular glues have not been exploited to anywhere near their full potential in large part because their development has been hampered by a lack of tools that tell us how they work. This project will adapt, refine and use a technique called native mass spectrometry to guide the design and optimisation of molecular glues. The native mass spectrometry approach for studying molecular glues was recently developed in our laboratories and has exciting potential for speeding up the optimisation of molecular glues. We will focus on the design and optimisation of glues that target the interactions of an important protein called 14-3-3 which plays a particularly important role in preventing and fighting cancer. Thus the project will deliver much needed novel cancer therapies which can ultimately be used to tackle hard to treat cancers or problems surrounding drug resistance. This is a highly interdisciplinary project that will provide world-class training in native mass spectrometry techniques, chemical biology and drug design.

Extension from 2 to 3 year fellowship--see case for support document