This proposal builds on - and extends to new audiences and user communities - our NDA funded research project (2009-2012) entitled Ages and Stages: The Place of Theatre in Representations and Recollections of Ageing. It aims to develop some of the activities and research-led learning from that project and, in so doing, reach out to - and bring together - user communities who may not traditionally have worked with drama in the ways proposed here. This will be achieved through the following connected programme of drama-related activities: 1) The formation of an intergenerational theatre company at the New Vic Theatre. Through a regular series of workshops, the company will bring older and younger people together in creative, drama-based activities to enhance understanding between the generations and support the continued social engagement of both groups. 2) A touring performance. The IG company will create a touring piece(s) which can be taken out to audiences within, and beyond, North Staffordshire. We anticipate that these audiences might include local councils; primary as well as secondary schools; residential homes/housing developments for older people; community groups and higher education institutions providing professional training courses (for teachers, social workers and doctors/nurses). 3) An inter-professional training course and training materials/resources, which will aim to develop practice capabilities and age awareness amongst teachers, health and social care professionals, arts practitioners and others interested in learning about and including intergenerational theatre/drama in their practice. The IG company will act as an important resource by contributing to the development and delivery of the training sessions and providing feedback to participants. 4) A scoping exercise for a wider 'Creative Age Festival', which could leave a concrete community legacy from Ages & Stages. The project will continue to be overseen by the existing 'Ages and Stages' Advisory Group, which includes experts in drama, intergenerational practice, policy and gerontology. The group will also be refreshed by new members, including younger members of the intergenerational theatre company (aged 16-18) . The activities we propose are timely for the following reasons. First, there is a notable groundswell of interest in the arts in general and theatre/drama in particular, not simply as a cultural activity but as one which has the potential to impact positively on the well-being of older and younger people. Second, in times of scarce resources, it is important to capitalise on activities which bring people together rather than those which might pit the generations against each other. Third, there is a role for practitioners in facilitating and enabling these kinds of activities but rarely, to our knowledge, have there been opportunities for professionals from differing arenas to work together as is proposed here. Finally, it is important to make best use of existing knowledge - not just that generated from our own work but also that of colleagues. We will be drawing strongly from our collaborators, including our linked Canadian project (about the impact of theatre on health ageing, which runs until 2013), and will also remain part of the New Dynamics of Ageing programme and will benefit from the knowledge exchanges this offers.

The shift from hunting and gathering to an agricultural way of life was one of the most profound events in the history of our species and one which continues to impact our existence today. Understanding this process is key to understanding the origins and rise of human civilization. Despite decades of study, however, fundamental questions regarding why, where and how it occurred remain largely unanswered. Such a fundamental change in human existence could not have been possible without the domestication of selected animals and plants. The dog is crucial in this story since it was not only the first ever domestic animal, but also the only animal to be domesticated by hunter-gatherers several thousand years before the appearance of farmers. The bones and teeth of early domestic dogs and their wild wolf ancestors hold important clues to our understanding of how, where and when humans and wild animals began the relationship we still depend upon today. These remains have been recovered from as early as 15,000 years ago in numerous archaeological sites across Eurasia suggesting that dogs were either domesticated independently on several occasions across the Old World, or that dogs were domesticated just once and subsequently spreading with late Stone Age hunter gatherers across the Eurasian continent and into North America. There are also those who suggest that wolves were involved in an earlier, failed domestication experiment by Ice Age Palaeolithic hunters about 32,000 years ago. Despite the fact that we generally know the timing and locations of the domestication of all the other farmyard animals, we still know very little for certain about the origins of our most iconic domestic animal. New scientific techniques that include the combination of genetics and statistical analyses of the shapes of ancient bones and teeth are beginning to provide unique insights into the biology of the domestication process itself, as well as new ways of tracking the spread of humans and their domestic animals around the globe. By employing these techniques we will be able to observe the variation that existed in early wolf populations at different levels of biological organization, identify diagnostic signatures that pinpoint which ancestral wolf populations were involved in early dog domestication, reveal the shape (and possibly the genetic) signatures specifically linked to the domestication process and track those signatures through time and space. We have used this combined approach successfully in our previous research enabling us to definitively unravel the complex story of pig domestication in both Europe and the Far East. We have shown that pigs were domesticated multiple times and in multiple places across Eurasia, and the fine-scale resolution of the data we have generated has also allowed us to reveal the migration routes pigs took with early farmers across Europe and into the Pacific. By applying this successful research model to ancient dogs and wolves, we will gain much deeper insight into the fundamental questions that still surround the story of dog domestication.

This project will quantify the effect of surface generated melt-water fluctuations on ice motion at the margin of the Greenland Ice Sheet (GrIS). More specifically, it will provide data that will enable ice-sheet modellers to improve their predictions of the future contribution of the GrIS to sea level rise in response to a warming world. To achieve this aim requires a dedicated field campaign to the GrIS to investigate seasonal ice flow dynamics and runoff processes along flow parallel transects extending from the ice sheet margin to the equilibrium line altitude (ELA) at both tidewater and land-terminating glaciers. The greatest store of fresh water in the northern hemisphere - equivalent to 7m of eustatic sea level rise - is held within the Greenland Ice Sheet (GrIS), and yet its present and future contribution to sea level is poorly constrained (IPCC, 2007). Recent observations suggest that mass loss near the margin of the GrIS is accelerating through a combination of increased surface melting (e.g. Steffen et al, 2004) and dynamic thinning (e.g. Rignot and Kanagaratnam, 2006). However, the key processes controlling dynamic thinning have yet to be identified (Alley et al, 2005), and in consequence, are not incorporated in the ice-sheet models which form the basis of the IPCC sea level projections. This in part reflects the fact that the satellite data that has revealed the widespread speed-up of glaciers cannot be acquired at the temporal resolution needed to resolve the causal mechanisms. Our present understanding of GrIS mass balance is especially complicated by uncertainties in the sensitivity of ice-marginal dynamics to changes in melt-water induced lubrication resulting from penetration of supraglacial melt-waters to the glacier bed (Zwally et al, 2002). Recent observations on the GrIS Shepherd et al, in review) reveal, over a five day period in July, a strong and direct coupling between surface hydrology and dynamics where diurnal fluctuations in velocity of >100% occur and where maximum daily velocities scale with temperature. Such observations confirm the need to acquire hydrological and dynamic data at high temporal (sub-hourly) and spatial resolution throughout the year to parameterise the coupling between ice melting and flow. This project will collect data at the necessary resolution to quantify the relationship between melt-water production and ice sheet dynamics thereby enabling ice-sheet modellers to improve predictions of the GrIS's response to climate change. We will conduct ground based experiments along two flow-parallel transects at the western margin of the GrIS in adjacent land and marine terminating drainage basins to address the following objectives: 1. Is there a temporal and spatial pattern to any hydrology-dynamic link associated with the seasonal evolution of the supraglacial drainage system (including supraglacial lakes)? 2. Over what area does surface generated meltwater penetrate to the base of the ice sheet? 3. Is there a relationship between the volume of meltwater input at the glacier surface and the magnitude of the dynamic response? 4. Do tidewater and land-terminating glaciers behave differently during the course of a melt-season? Field campaigns will be undertaken during 2008 and 2009 to determine: 1) The rate, extent and duration of melt. 2) The temporal and spatial variations in water volumes stored in and released from supraglacial lakes and delivered to freely draining moulins. 3) The seasonal, diurnal and hourly variations in ice dynamics. 4) The variations in proglacial discharge and water chemistry (at Russell Glacier). As a result of our work, it will be possible to determine whether ice dynamics at the margin of the GrIS is significantly affected by lubrication of the glacier bed following the drainage of surface derived meltwaters. Our results will be delivered to ice sheet modellers to help them constrain predictions for the future of the GrIS

Transition zone seismic discontinuities (TZSDs), manifestations of mineral phase transitions or/and compositional changes between the upper mantle and the lower mantle, hold the key to resolve the mystery of mass and heat transport in the Earth's mantle and the long-term evolution of the Earth's interior. However, seismic characterizations of TZSDs are typically incomplete because of the limit in the data frequency bandwidth and sensitivity relevant to TZSDs. We innovate a simple, effective and high resolution probing of mantle discontinuity through examination of broadband forward and backward scattering waves in the context of the teleseismic receiver function method. This approach will allow us to comprehensively characterize TZSDs beneath the continents, including properties such as discontinuity topography, sharpness and gradient, shear velocity jump and density jump. To date, there has been no single study that is capable of simultaneously determining these essential seismic properties in the TZSDs. These renewed descriptions of TZSDs will be used to explore outstanding questions including mineralogical models of the transition zone and the presence of volatile/melt. In particular, we aim to address how current and past subduction determine short-term and long-term mantle mixing and whether such a mixing process may in turn shape slab sinking dynamics. A series of outstanding questions can be much better addressed with our new seismic observations: Did long-term mixing of billions of years result in apparent chemical layering as indicated in geodynamic models? What are the degree and the length scale of lateral heterogeneity if such a chemical layering exists? Is it possible that primordial structure may survive long term mixing and become trapped in the transition zone? Is the transition zone potentially a relatively shallow reservoir for long-term storage and geochemical evolution of basalt? Does chemical layering or large-scale primordial structure dictate the slab sinking dynamics? Does modern and ancient subduction recycle water into the deep mantle and transition zone? Does hydrated transition zone induce convective instability and contribute to intraplate volcanism? In the proposed work, we will use an innovative and effective observation with broadband forward and backward scattering waves to provide a comprehensive characterization of TZSDs, including properties such as discontinuity topography, sharpness, velocity and density jumps across the boundaries, and the gradient above/below the discontinuities. These unprecedentedly rich observations will provide renewed constraints on fundamental processes relevant to the Earth's interior and evolution.

Neurodevelopmental disorders (NDDs) represent a heterogeneous group of conditions that persist throughout life, and affect more than 3% of individuals worldwide. NDD has a major impact on the affected individuals, families and society as a whole. Due to high-throughput sequencing, up to 50% of NDD cases are diagnosed as a monogenic cause. Our consortium specifically focuses on pathogenic variants in genes encoding components of the ubiquitin-proteasome system (UPS) associated with NDDs. The UPS ensures the selective degradation of proteins through a complex ubiquitination process involving >1,000 distinct ubiquitin ligases, which prepare these proteins for degradation by the 26S proteasome. The UPS is essential for cellular homeostasis and a vast number of genes are involved, most of them abundantly expressed in brain. It is therefore not surprising that 10-15% of NDDs have been associated with UPS dysfunction. The partners of our UPS-NDDiag consortium have identified more than 250 pathogenic or likely pathogenic variants across >30 UPS genes associated with NDD. However, the complexity of the system causes major challenges in assessing the pathogenicity of genetic variants, and good biomarkers that indicate UPS dysfunction are largely lacking, hampering diagnosis. Our consortium is structured around six interconnected work packages. These will be addressed by six partners from five countries with complementary skills and outstanding expertise in advanced genetics, functional genomics; facial recognition for diagnosis of rare diseases; functional studies in hIPSCs, Drosophila and mice; bioinformatics; integrative analysis of multi-omics, and pharmaceutical nanotechnology. In addition, 26 international collaborators join the consortium to enrich its knowledge and skills. Our main delivery is to provide reliable biomarkers and functional assays to classify UPS-related variants. Besides, UPS-NDDiag will yield therapeutic targets that may support drug development for personalized medicine and shed light on our current understanding of the overall pathogenesis of disorders related to the UPS.