The commonest visual disorder of children is amblyopia (lazy eye), which affects 2-4% of the population. This project explores potential avenues for treating amblyopia in adulthood. Amblyopia is defined clinically as a deficit in visual acuity despite optimal refractive correction, due to some disruption of normal visual development during childhood. Amblyopia is usually treated by occlusion therapy (covering the good eye for a period of time to enforce the use of the amblyopic eye). The effectiveness of this procedure decreases with age. To date, it is not possible to restore normal vision in an amblyopic eye after the age of 8 years, the end of sensitive period of cortical plasticity. This project aims at restoring visual cortical plasticity in adulthood. We know that in the adult brain, the ability of neurons to form new connections is limited by a mesh of molecules surrounding them, the extracellular matrix, which becomes more and more rigid during adolescence. We plan to infuse enzymes into the visual cortex that will loosen up that matrix, and additional substances that are known to promote the outgrowth of neuronal processes. We hope that this combination strategy will reverse the loss of functional connections from the deprived eye to the visual cortex. We will employ functional brain imaging to assess whether visual cortex responses to stimulation of the amblyopic eye will have returned. We will test and refine our treatment using animals, and later on hope to develop it further for amblyopic patients who have suffered loss of vision in their good eye through illness or injury and have therefore become blind or severely visually impaired.

Depression is the second most common illness in primary health care and disrupts the everyday functioning of over 100 million people worldwide. Depression is a severe mood disorder that is characterised by clinical features such as anhedonia (a loss of pleasure in previously enjoyable activities), cognitive and emotional impairment, psychomotor retardation, and disturbances in sleep and appetite. 20-40% of all patients do not benefit from traditional treatment methods such as psychotherapy or anti-depressant medication. This project will investigate a potential new treatment method: functional magnetic resonance imaging (fMRI)-based neurofeedback. In this method people undergo fMRI-scanning and receive continuously updated feedback about the activity level in a certain brain area, which they use to learn to control their own brain activity. It has previously been shown that chronic pain patients experienced considerably less pain after exercising control over a brain area involved in pain processing. In our project feedback from a region involved in positive emotion processing will be provided so that depressed patients can learn to regulate their emotional state. A pilot study of this method from our group has shown that depressed patients are both able to regulate their emotional network and experience significant improvements in mood.

Cytomegalovirus is closely related to the herpes virus that causes cold sores. Like herpes, CMV is carried for life and can reactivate at any time to cause disease. Most people worldwide are infected with CMV, yet do not know. In hospitals , however, CMV is well known and recognized to be an important pathogen. CMV can cause severe multi-organ disease in individuals whose immune system is suppressed by drugs (bone marrow, heart or kidney transplant recipients), compromised by HIV-AIDS and also when the virus crosses the placenta to infect the foetus. CMV is the largest and most complex of any human virus, estimated to have some 184 genes. CMV researchers have increasingly been concerned about the viruses they have been using in the laboratory. CMV has evolved with us to grow in us. Before the virus will grow in vitro it mutates and changes; always the same genes first: RL13 and UL128 first. We already know a fair bit about UL128. Counterintuitively, RL13 suppresses the growth of CMV in all cell types. Why would a virus do that? We suspect it is to allow the virus to persist and spread in our tissue without alerting the immune response. Since this gene has a major effect on virus growth, it is crucial to work out what it is doing and how. Moreover, it is important to work out how to grow and work with the virus that causes clinical disease. Up until now, our understanding of CMV has been almost exclusively based on work with mutant viruses. What do these ~184 genes do? Surprisingly only a minority are needed by the virus to grow, the majority appear to be there to control us and our immune system! As most of us carry the virus, this is a major concern. CMV is known to alter the repertoire of out white blood cells even in healthy carriers. We have nearly finished cloning all 184 genes into a different (replication-defective/disabled) virus, so we can study all CMV?s genes individually. Using this gene library and high throughput screening systems we seek to identify characterise as many of the key immune regulatory genes in this virus as possible. The more we know about this virus, the better we can manage disease and develop antiviral strategies.