Human cytomegalovirus (HCMV) is a virus which is carried without symptoms by the majority of the population. However, it can cause serious disease in infants born to mothers who acquire the infection in pregnancy and in people whose immune system is suppressed. Understanding how the virus succeeds in maintaining itself in most people without causing disease and how this relationship breaks down to cause disease should help develop better methods of treating the virus and of designing a vaccine (there is currently no vaccine available). Our research is aimed at determining (i) how the virus gains control of the cell in order to reproduce itself (ii) the mechanism by which the virus maintains silent infection ( latency ) in specialised cells of the immune system and the factors that reawake it and (iii) how the immune system controls the infection in normal people. We shall then extend our work to try and generate useful immune responses in patients at risk of infection. In addition to advancing our understanding of HCMV in particular, this research may also lead to a better understanding of other virus infections which persist in the body, and how the human host controls them.

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.

Many adult tissues are maintained by stem cells. Failure to control the generation of stem cells or the differentiation into their progeny contribute to cancer. Thus, the goal of this project is to identity key regulators and mechanisms that control the maintenance of healthy skin by regulating stem cell growth and differentiation. Once we have identified important factors regulating stem cell fate, we further investigate whether their mis-regulation contribute to cancer. These approaches are being developed and exploited to uncover novel mechanisms and pathways that are involved in cancer development and could well lead to the discovery of novel anti-cancer drug targets.

Emotions are highly adaptive and complex states, which include our internal feelings, e.g. happiness or fear, our physiological reactions, e.g. sweaty palms, racing heart, and our behavioural responses e.g. approaching something nice and avoiding something harmful. They are triggered by stimuli in the environment, that through past experience, have gained emotional significance. However, our immediate reactions to such emotive stimuli are not always beneficial, and we need to be able to adapt and rapidly modify our emotional responses on a moment-by-moment basis, whether it?s in the workplace, or at home. The ability to regulate our emotions is essential for our physiological, psychological and social well-being and when this ability is impaired it can have a profound, deleterious impact on us. This is illustrated by the range of neuropsychiatric disorders in which emotional disturbance is a core feature, including anxiety, depression, schizophrenia, autism and sociopathy. Anxiety disorders alone have a lifetime prevalence of 16%. It has been shown that in many of these neuropsychiatric disorders there is pathology in various regions of the brain, including the orbitofrontal cortex and amygdala. In addition, there are also imbalances in a number of chemical messengers in the brain, including serotonin. Indeed, many drugs used to treat these neuropsychiatric disorders, target serotonin. However, exactly how these brain regions contribute to emotional regulation, and the role played by serotonin, is poorly understood. We will investigate this by modelling their effects in the brains of experimental animals performing behavioural tests that measure their ability to regulate their emotions. The benefits provided by this Programme lie eventually in understanding how these different regions of the brain control our emotions and how serotonin modulates these brain regions. This information is critical for our ability to develop novel therapies, as well as target current therapies more effectively, for a range of neuropsychiatric

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.