Aims To define the pathways involved in tumour formation, and to target these pathways with novel, preclinical agents. Objectives: 1) To identify pathways in cylindroma formation by: a) Gene expression profiling of human cylindroma tissue, to identify the key regulatory pathways, abrogation of which are associated with tumourigenesis. b) To confirm the gene expression microarray results by secondary techniques, namely, immunohistochemistry, quantitative PCR and Western blot analysis. 2) The development of a primary cylindroma cell line: a) To allow the investigation of biological functions of novel therapeutically relevant pathways, as highlighted by the array data. b) To be the basis of a drug-screening assay to test preclinical agents that target the abrogated pathways defined above. The ultimate goal will be to begin clinical trials of non-surgical treatments in FC, to improve quality of life, prognosis, and outcome.

Primary Biliary Cirrhosis (PBC) is a liver disease that predominantly affects females, can present for the first time at any age, and which develops over many years. It is caused by the immune system attacking the body’s own tissues. People with PBC frequently experience profound fatigue or tiredness which they liken to their “batteries running down”, and although people still want to undertake normal activities they simply lack the energy to be able to do them. This reduces quality of life, makes it difficult for people to work, and can end up with them becoming isolated in the community. At present we have no treatment for fatigue in PBC. Finding a treatment for fatigue in PBC is one of the highest research priorities identified by patient groups. We have shown that PBC patients with fatigue have an abnormality in the way they generate energy within their muscles. This appears to be associated with the presence of an antibody in the blood which is directed against an important protein which normal cells in the body use to generate energy. In recent years new drug treatments have been developed which allow us to safely suppress the part of the immune system which produces antibodies of the type that seem to cause energy production problems in PBC. As yet, however, the extent to which these medicines can improve fatigue through removal of antibodies in PBC has not been tested. The aim of this study is to undertake a clinical trial to examine the effects of this treatment (“Rituximab”) on severe fatigue in PBC to help us understand whether this will be a potentially useful treatment. The information this will give us about how energy generation changes in patients with PBC with and without the treatment will also help us to develop new treatments for fatigue in other diseases. The study has the potential to improve the quality of life of many patients with PBC, for whom there is currently no hope of improvement. We will perform a randomized controlled trial of Rituximab therapy in PBC compared to placebo with the primary end point of fatigue severity. The study will be performed in a specialised PBC clinical centre. Money is requested for the costs of the treatment, the staff to carry out the assessment of patients and supervise the safe and successful completion of the trial, and also for the laboratory and body-scanning costs. We have, for many years, worked closely with PBC patient groups to focus on the problems that are important to our patients. This proposal reflects these close links and is fully supported by LiverNorth, a liver disease charity and patient support group.

This project aims to devise and implement a new tool for the sustainable management of cultural heritage. The RES.CO.PART tool will promote the efficient involvement of communities as stakeholders in decision-making processes for the management of cultural heritage in landscape. It will combine interdisciplinary methods of spatial analysis (especially Geographic Information System (GIS) based Historic Landscape Characterisation (HLC)) in a new way with research practices from cultural anthropology. The tool will help bridge the gap between theoretical appreciations of cultural heritage and the management practices that are actually applied on site. The tool will be developed through practical case-studies in two contrasting communities, Naxos in the Aegean Sea (Greece) and part of the East Devon ‘Area of Outstanding Natural Beauty’ (AONB) (UK). To implement this project, Dr Stelios Lekakis will move from Greece to Newcastle University in the UK, undertaking systematic training in GIS-related methodologies and especially the HLC tool, along with related skills in the visualisation of results for the public. The project results will be disseminated through a specifically designed open platform. To create this, he will also be trained in the process of building a digital, open-access tool for the collection and communication of relevant data by interested stakeholders.

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.

My friend Thomas is an artist but whenever we look at the same things he illuminates an important problem in neuroscience. He sees things differently from me. In bland walls he sees the plaster’s structure nicely contrasting the weathered chromium green of a nearby car. Thus, his pictures of boring environments make great paintings. Thomas’ exceptional visual abilities have been honed by years of training and practice as an artist. But those abilities must be supported by real differences in his brain. Where do these differences reside? How do they come about? And what are they? To become better at ‘seeing things’ and at discrimination tasks is referred to as perceptual learning. The mechanisms that mediate perceptual learning and the locations in the brain are still poorly understood. We will investigate (1) where in the brain perceptual learning occurs, and whether there a hierarchy of perceptual learning? (2) How does attention influence perceptual learning? (3) Which brain chemicals mediate perceptual learning? Answers to these questions will improve our understanding of learning in general and may pave the way to better regeneration of brain function following brain injury and better therapy for learning disorders.