Abstract not currently available

Most cells within the body contain exactly the same information - identical DNA strands - but look and behave differently. Exactly how each cell is educated to do a specific job is not understood. What seems to be important is that cells turn on and turn off the right genes at the right time and in the right place. We are trying to figure out how information contained within the DNA of our genes is used to instruct a developing embryo to make cells with a particular function. If this were understood, it may be possible to safely convert cells of one type to do a different job. For example, to divert cells that you dont need or are in surplus, to repair important tissue that is damaged by injury or disease. This tremendous potential for therapy provides additional incentive for trying to solve how cells make their different career choices and whether these choices are permanent or flexible.

Addiction to opiates and to alcohol is a major cost to the public both in terms of ill-health and in crime and policing. Intoxication with these drugs has huge costs to society in terms of accidents and violence. Together these costs have been estimated as equivalent to those of all other psychiatric disorders combined (ca. #4billion p.a. in the UK). Understanding the actions of these drugs in the brain is a necessary component in combating these problems. We are trying to identify the brain mechanisms of addiction to, and pleasure from, these drugs. We know that drugs including alcohol act by changing chemical messengers in the brain called neurotransmitters. Our study tries to show how these are altered in people addicted to heroin or alcohol. We also want to understand how treatments work, so we also study the effects that current treatments have in the brain to help design new and better ones. This could have big implications for health and reduce the costs of the damage that these drugs do to society. It may also lead to new investment from pharmaceutical companies which are one of the UKs leading wealth-creating industries. This work continues our successful previous research which uses the newest scanning technique, positron emission tomography (PET). This allows us to directly measure levels of neurotransmitters and their receptors in the human brain. We also perform studies using drugs to alter these neurotransmitter systems to investigate how they are functioning in healthy individuals and those that are addicted. We focus on three key neurotransmitters in addiction- the dopamine system involved in mediating pleasure, the GABA system, the brains natural calming system that mediates many effects of alcohol, and lastly the opiate system which mediates many effects of opiate drugs such as heroin and also the pleasurable effects of alcohol.

Modern biology is becoming more and more multidisciplinary. This is especially the case for the area of 'Systems Biology', which aims to predict how the different biological processes interact to result in a functional organism. These processes include the transcription of DNA into RNA, which codes for amino acids that make up the proteins, as well as the levels of hormones and metabolites that affect the biological processes. In the proposed network, we address how variation at the DNA level affects the transcription of DNA into RNA and how this then affects the characteristics of the whole organism. The aim is to reconstruct the networks that describe how genes interact. While conceptually straightforward, the area of research requires integration between biology, computer science (bioinformatics) and mathematics. At present, there is already some level of integration between researchers in these areas, but a lot of work is done in isolation. In the proposed network we will bring together: 1) biological research in plants, animals and humans. 2) Bioinformatics research which covers databases that contain known information on gene networks but also translates novel statistical and mathematical models into user-friendly software. 3) Mathematical biology, focussed on the methods of reverse-engineering of gene regulatory network, from a variety of experiments. The network will achieve its goal of further integration by organising annual meetings. These meetings will consist of an interactive workshop followed by a scientific conference. The workshop will provide ample opportunity for training of young researchers, dissemination of 'best practise' and new software tools and initiation of new collaborative research. The Conference will disseminate the cutting edge of the research area to the wider community.

The research of the Physiological Genomics and Medicine Group uses information and technologies from the Human Genome Project to improve understanding of the molecular basis of common diseases and to find new ways of diagnosing these disorders and predicting which individuals will develop them. The approaches used have found new genes underlying the common Metabolic Syndrome which predisposes to late-onset diabetes and coronary heart disease, and also showed that variation in the number of gene copies carried by an individual can be a cause of kidney failure in the common human condition systemic lupus. These findings suggest new ways of disease diagnosis and new targets for drug therapy of these conditions.