The Kavli INsD's Brain Health research theme brings together scientists across disciplines to address major research challenges related to the brain. A large portion of our research in this area relates to dementia and neurodegeneration, sleep and circadian rhythms, and mental health. The genetic and mechanistic basis for migraine headaches is another area of focus, led by Zameel Cader.
Our research aims to improve understanding of the mechanisms underlying conditions such as Alzheimer's and depression and the role of the body clock in health and disease. Ultimately, we aim to translate that understanding into better strategies for disease prevention, diagnosis and treatment.
Dementia and neurodegenerative diseases, including Alzheimer’s, Parkinson’s and motor neuron disease, represent an increasing healthcare burden for an ageing global population. Largely untreatable, these diseases are already a leading cause of disability and their prevalence is rising.
Our research aims to understand the fundamental biological processes that underlie normal brain development and are responsible for neurodegeneration, and to inform the development of treatments. Our work relies on diverse models, ranging from in vitro systems to cellular models, such as induced pluripotent stem cells (iPSCs), as well as on human tissue samples. The ability to generate, engineer, differentiate and phenotype iPSC-derived neurons and glia from healthy people and those with neurodegenerative disorders makes it possible to study relevant human models of disease.
For this research, we develop and make use of a rich array of experimental tools, which include mass spectrometry, NMR spectroscopy, cryogenic electron microscopy, genome editing, X-ray crystallography, and super-resolution microscopy. These techniques, combined with computation tools, enable detailed characterisation of relevant biomolecular interactions, structure and dynamics.
We also benefit from links with the Oxford Parkinson's Disease Centre, the Oxford Motor Neuron Disease Centre, the Translational Neuroscience and Dementia Research Group, and the ARUK Oxford Drug Development Institute.
Our work in this area focuses on:
- Identifying the genetic regulatory pathways involved in normal and aberrant neurodevelopment as well as susceptibility to neurodegeneration (Noel Buckley, Richard Wade-Martins)
- Understanding the molecular mechanisms of protection against protein mis-folding and aggregation, and the role of molecular chaperones in particular (Justin Benesch, Andrew Baldwin)
- Exploring the formation of complex tissues, including neural networks (Elena Seiradake)
- Identifying therapeutic targets for treatment of motor neuron diseases (Kevin Talbot)
- Elucidating the molecular and cellular mechanisms of cerebellar ataxia, and identifying potential therapeutics (Esther Becker)
- Investigating protein trafficking and degradation pathways in Parkinson’s disease and their translation into potential targets for therapies or biomarkers (George Tofaris)
- Studying regulation of the lysosome, a metabolic signalling hub that plays a role in the degradation of protein aggregates and neurodegeneration (Simon Newstead)
- Identifying and validating new drug targets and signalling pathways involved in blood-brain barrier dysfunction in neurodegenerative diseases and brain injuries (Mootaz Salman)
- Understanding the cellular basis of cognitive resilience to Alzheimer’s Disease pathology (Becky Carlyle)