Background Mental health is a major cause of disability. Some people with squint and related conditions are more likely to be affected. Most studies that have looked at squints or related nervous system and eye related problems do not have enough information to assess mental health outcomes. Large studies, such as Children of the 90’s, Generation Rotterdam, RAINE study (Western Australia) and UK Biobank, hold lots of eye, genetic and mental health information that can be used to measure the effect of squint on mental health. Research Approach - Use eye and mental health information from large studies to see how and why squint affects mental health - Use a combination of observational and genetic information from large studies (with multiple eye related measures and mental health records) to measure how much squint affects mental health - Interview people with squint to see how squint and patient’s hospital care affected their mental health Impact - Understand how squint and related conditions affect mental health - Think of new ways to reduce the risk of poor mental health for people with squint - Help the NHS and its funders make policy for how to treat people with squint.

Alzheimer’s disease (AD) arises through the aggregation of amyloid-β (a cleavage product of APP) and tau protein throughout the brain. The build-up of these proteins can result in harmful changes to neuronal functioning and health, including dysfunction of mitochondria, which are responsible for energy production within the cell, and changes to the way neurons communicate with each other at synapses. My project aims to express AD-causing mutant forms of APP and tau proteins in primary neuronal cultures to generate a sped- up model for neurodegeneration in AD. Upon validating these models with regards to neuronal health and production of neurotoxic proteins, the models will then be used to investigate the changes to mitochondria morphology and proteins controlling this. Using a mixture of protein biochemistry, immunofluorescence imaging and potentially electrophysiology, I will detect changes that occur when either or both of these neurotoxic proteins are expressed to dissect each proteins’ role in mitochondrial dysfunction. Further to this, the cellular localization, surface expression and activity of synaptic proteins including AMPA receptors and CB1 receptors will be investigated following expression of these neurotoxic proteins. This work could help to find new points of intervention to slow dementia in AD.

Identifying disease-associated genes, mutations and perturbed expression is only the first stage towards understanding human disease and the development of therapeutics. In Bristol we aspire to understand gene function and the proteins they encode across spatial scales, from the molecular level through to functional studies in cells, tissues and organisms. Since proteins, cells and tissues are all dynamic, wherever possible these processes need to be studied through multiple timescales. Advances in spatial and temporal resolution of microscopy provide opportunities to study processes at an unprecedented level across molecular and cellular scales. Only by combining these approaches will we truly understand organismal-level health, the pathoetiology of diseases and provide rational therapeutic routes to relieve them. This relies on biologists operating at the interface between molecular and cell biology. Our Wellcome programme will recruit, support and train a new generation of PhD students in Biomedical Research, with a broad base and understanding of molecular cell biology techniques coupled with world-class expertise in their PhD topic. These students will be trained to become future leaders in a wide range of careers, founded upon a holistic and rounded personal and professional development, which incorporates the best practice in PhD training.