Enteroviruses are common and important human pathogens. While many infections are mild, some strains can cause severe and even fatal disease with symptoms ranging through fever, hand foot and mouth disease, myocarditis, viral meningitis, encephalitis, acute hemorrhagic conjunctivitis, and acute flaccid paralysis. Although poliovirus (the enterovirus that causes poliomyelitis) has been eradicated from much of the globe it remains a threat, and other emerging enteroviruses can also cause severe polio-like symptoms. Currently, vaccines are only routinely available for poliovirus (approved globally) and EV-A71 (approved in China). Enteroviruses are also some of the best studied viruses and serve as a useful model system for understanding the biology of all "positive-sense" RNA viruses which can be found in every virology textbook. The enterovirus genome is ~7400 nucleotides in length and, ever since poliovirus was first sequenced in 1981, was believed to encode only 11 proteins, including enzymatic proteins that replicate the viral genome and structural proteins that package progeny genomes into protein capsids for transmission. These 11 proteins are translated from the genome (which functions directly as a messenger RNA) concatenated end-to-end as a single giant "polyprotein", which is then cut up by one of the viral proteins (a proteolytic enzyme) into the 11 virus proteins. However, we recently showed that this picture was incomplete: in fact one more protein is cryptically encoded within the genome of many enteroviruses. We call the additional protein UP (Upstream Protein) since it is encoded upstream of the polyprotein. Using an organoid system ("mini gut" 3d cell cultures grown in the lab), we went on to show that UP plays an important role specifically in gut epithelial cells where it is involved in releasing newly formed virus particles from membranous compartments. This is exciting because the gut is the site where enteroviruses first replicate on infecting a new host before, potentially, invading other cell types and organs. In contrast, the closely related rhinoviruses replicate in the upper respiratory tract and - perhaps not surprisingly - they ubiquitously lack the UP protein. We published this research in Nov 2018 in Nature Microbiology. However this previous work just scratched the surface of understanding the biological function of the novel UP protein. Many very important questions remained unanswered, such as why do some enteroviruses appear to lack the UP protein, how does UP differ between different enteroviruses, what controls UP expression, with which membranes does UP associate, and how exactly does UP function to facilitate release of virus from membranous compartments. Through five work packages, we will now perform a detailed functional analysis of the UP protein: 1) Bioinformatic analysis - correlation of UP with virus provenance and clinical data 2) Assessing and deciphering the regulation of UP expression 3) Biochemical and functional characterization of the UP protein 4) Biological functionality of UP in human intestinal organoids 5) Physiological role of UP and potential as a vaccine candidate This research is exciting for several reasons. The discovery of a new protein opens up a whole new avenue for enterovirus research that will give new insights into virus biology and pathogenesis. We are ideally poised to exploit this new research direction. Understanding the function of UP may also help explain why some enteroviruses can infect the gut whereas others infect the upper respiratory tract. These findings may aid rapid prediction of the tropism of newly emerging enteroviruses. More importantly, UP knockout viruses could be ideal candidates for attenuated virus vaccines since they grow well in cell culture (to give good vaccine yield) but are attenuated in the gut; further, this strategy could be quickly applied to newly emerging enteroviruses.

Many people with dementia face challenges in trying to live with such a socially stigmatising diagnosis. The World Alzheimer's Report (2011) suggests that when people with dementia and their families are well prepared and supported around the diagnosis and post diagnosis, then initial feelings of shock, anger and grief are balanced by a sense of reassurance and empowerment. However, how (and if) people are told they have dementia varies widely depending on national policy and practice. Effective diagnosis sharing is a fundamental first step in any person centred approach to dementia care. Many countries are moving away from medical approaches to give more focus on person centred dementia care. There is increasing evidence around the positive benefit and impact people with dementia can bring to their own care contexts. For people with dementia this means that issues of involvement and participation, as well as positive social relationships and being connected to their community, are all important to how they live with their diagnosis. Wider family and support relationships are part of the overall picture around living with dementia, yet what we know about these relationships is limited. The research focus of this proposed international group will be to improve our understanding of how relationships work after a diagnosis. Knowing more about how relationships work will help dementia researchers, people developing national policy, people providing support and care services, and for people with dementia themselves. Internationally, each of the 3 partner countries is experiencing and predicting rapid growth in the numbers of people with dementia. The UK now has guidance and national policy on diagnosis sharing and post diagnostic support. More globally, findings from the 10/66 Dementia Research Group show a more mixed picture. In Goa, the focus on diagnosis sharing and person centred care is a very recent development. In Taiwan the number of people with dementia is expected to increase dramatically. Taiwan has a national Ten-Year Long Term Care Plan started in 2008, so person centred care is a recent development. The proposed project will support established and early career dementia researchers from UK, India and Taiwan to work together. This group will meet at a four day residential in Edinburgh in August 2012 planned to coincide with conference attendance in Scotland by the senior academics. This meeting will be an opportunity for the group to plan and write an application for research funding. The overall aim of the proposed project is to support this existing group of academics to form stronger working relationships through which to share varied national perspectives; and to agree and take forward a joint research funding proposal that will explore post diagnostic relationships for people with dementia. Longer term impact will focus on activity and outcomes relating to grant applications, collaborations and publications. The partners have been chosen to allow for a variety of practice and policy contexts and to build on and strengthen existing academic and practice relationships. Prof Shyu, from Cheng-Gung Univesrity in Taiwan has a well established career focusing on dementia care and nursing. Dr Dias is a senior academic in the Dept of Preventative and Social Medicine, Goa Medical College and is also internationally connected to many of the major dementia networks including the 10/66 Dementia Research Group. Edinburgh University will provide desk, computing, library and other academic facilities to overseas participants who would like to extend their stay as a Visiting Fellow in order to add to the individual research capacity and experience, particularly for early career researchers. Dr Heather Wilkinson will project manage to ensure event coordination, impact assessment, building and sustaining network opportunities and dissemination. The CRFR knowledge exchange team will provide project support.

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.

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.

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.