Age-Related Diseases (Wolfson Centre for)

The recent explosion of data in the biological sciences driven by advancements in molecular biological technologies has made bioinformatics an integral part of biological research. At the Wolfson CARD bioinformatics covers research in structural biology and rational drug design as well as computational and theoretical approaches to database analysis. The big challenge addressed is to integrate the vast amount of deposited freely available biological data into a predictive framework for generating novel hypotheses to inform experiment and to identify drug targets. Once target proteins have been validated the challenge then is to characterise the structural aspects of the protein interaction and then design modulators either based on mimetics of peptide fragments or in silico screening of compound libraries

Scientists in the Wolfson Centre for Age-Related Diseases (CARD) are best known for their academic work on the molecular mechanisms that are involved in neurodegeneration, axonal regeneration and pain. The Neuroscience Drug Discovery Unit capitalises on our academic work. We have high throughput screening equipment, dedicated bioinformatics support with a molecular modeling and virtual screening capability and we run a number of in vitro and in vivo assays for target validation. The ultimate aim is the development of new medicines for neurodegenerative diseases and pain. The director of the unit is Dr Jonathan Corcoran who has been awarded two Wellcome Trust Seeding Drug Discovery grants (a total of over £7.5M) for the development of drugs for Alzheimer's disease and Spinal Cord Injury. The initiative will allow the College to pursue its commitment to translational research with pharmaceutical partners of excellence, supported by highly productive interactions between academics within the CARD and colleagues within King's Business

Scientists in the Wolfson Centre for Age-Related Diseases (CARD) are best known for their academic work on the molecular mechanisms that are involved in neurodegeneration, axonal regeneration and pain. The Neuroscience Drug Discovery Unit capitalises on our academic work. We have high throughput screening equipment, dedicated bioinformatics support with a molecular modeling and virtual screening capability and we run a number of in vitro and in vivo assays for target validation. The ultimate aim is the development of new medicines for neurodegenerative diseases and pain. The director of the unit is Dr Jonathan Corcoran who has been awarded two Wellcome Trust Seeding Drug Discovery grants (a total of over £7.5M) for the development of drugs for Alzheimer's disease and Spinal Cord Injury. The initiative will allow the College to pursue its commitment to translational research with pharmaceutical partners of excellence, supported by highly productive interactions between academics within the CARD and colleagues within King's Business

Understanding neurodegeneration is key to developing and taking forward new treatments for Alzheimer's disease, Parkinson's disease and stroke. Central to our approach is translating basic science into improved clinical treatment. Key elements of our work include experimental studies to understand basic disease mechanisms, the Brains for Dementia Research initiative, enabling us to apply this understanding to the human brain, and a substantial focus on biomarkers and clinical trials. Major clinical trials have addressed psychiatric and behavioural symptoms associated with dementia and the use of antipsychotic and sedative drugs. The Neurodegeneration group is led by Professor Clive Ballard.

The dogma for most of the last century was that the neurons we are born with need to last us a lifetime as all of the evidence suggested that we cannot make new neurons in the adult brain. There has now been a dramatic scientific U-turn, and not only do we continue to make new neurons in the brain, but this turns out to be important for some aspects of learning and memory and possibly brain disease. In the adult brain, neural stem cells make neuroblasts that populate the hippocampus or olfactory bulb with new neurons. Importantly, neuroblasts can also be attracted to injured areas in the brain where they might limit damage and/or restore function. In-depth knowledge of the factors that regulate the generation of neuroblasts as well as their migration is therefore essential to facilitate translational research in this area. A number of groups in the CARD, including the Director's group, are actively studying many aspects of neurogenesis

The dogma for most of the last century was that the neurons we are born with need to last us a lifetime as all of the evidence suggested that we cannot make new neurons in the adult brain. There has now been a dramatic scientific U-turn, and not only do we continue to make new neurons in the brain, but this turns out to be important for some aspects of learning and memory and possibly brain disease. In the adult brain, neural stem cells make neuroblasts that populate the hippocampus or olfactory bulb with new neurons. Importantly, neuroblasts can also be attracted to injured areas in the brain where they might limit damage and/or restore function. In-depth knowledge of the factors that regulate the generation of neuroblasts as well as their migration is therefore essential to facilitate translational research in this area. A number of groups in the CARD, including the Director's group, are actively studying many aspects of neurogenesis

Chronic pain is a debilitating disorder that affects millions of people world-wide and has a considerable detrimental impact on quality of life. There are multiple events which can lead to chronic pain including trauma, diabetes, surgical procedures, cancer and HIV. Effective analgesic therapies are inadequate in the majority of chronic pain patients and are often associated with unpleasant side-effects. Consequently at present there is a substantial, unmet, clinical need for more effective analgesics for chronic pain patients.

The transduction and transmission of signals throughout the body depends on the integrated activity of receptors, ion channels and enzymes in the nervous system and other tissues. The major interest of the Receptors, Channels & Signaling group is to understand the mechanisms that operate under normal conditions and during disease. Studies within the group are focused on the mechanisms of sensory transduction and signaling in neuronal and neuroendocrine cells, the regulation of neuronal excitability, and the signaling mechanisms responsible for neurogenesis and neural cell migration. This group comes together under the direction of Professor Stuart Bevan.

There are two main focuses within the Regeneration theme in the Wolfson CARD: spinal cord injury and stroke. Spinal cord injury results in severe disability and there is currently no cure. However, recent advances have been made in identifying and targeting factors that prevent repair after injury. For example, work in the Bradbury lab has led to the development of an enzyme therapy that can digest inhibitory molecules associated with the spinal injury glial scar. This therapy has shown great promise in pre-clinical studies and can promote axon regeneration, neuroplasticity, neuroprotection and, most importantly, recovery of motor function. Determining the mechanisms underlying these effects and developing optimised and targeted therapies is a key focus of ongoing studies within the Regeneration group. Another key focus of the Regeneration group is to optimise the function of surviving systems to promote repair, since spontaneous functional recovery is known to occur in the majority of spinal injured and stroke patients. Strategies to enhance these processes by promoting plasticity and thus inducing compensatory changes in undamaged pathways and reorganisation of spinal circuits are likely to be a major component of future therapeutic intervention.