We aim to understand nervous system formation, function and repair.
Our current focus is on understanding myelinated axon biology. Myelinated axons are the major componenet of our white matter, which represents about half the volume of our brain and spinal cord. Myelinated axons are the information superhighways of our nervous system, and thus are essential for its function. The presence of myelin on axons greatly accelerates the speed and information propagation along axons, and also provides important support to axons. It is now clear that the myelination of axons is something that continues long after birth, and even in to adult life, and it is now thought that dynamic regulation of myelination, and of myelinated axons in general may be a fundamental way in which brain function is modulated. Unsurprisingly, disruption to the formation or health of myelinated axons is associated with many diseases including including neurodevelopmental disorders such as autism, psychiatric conditions like schizophrenia, and neurodegenerative disorders including multiple sclerosis (MS). We are now learning a great deal about how the myelin producing glial cells of our brain and spinal cord (oligodendrocytes) are generated, about how these cells communicate with the axons that they myelinate, and how dynamic conversations between our axons and glial cells orchestrate myelianted axon function throughout life. Continuing to improve our understanding of myelinated axon biology is essential to gaining insight into how disruption to myelinated axons lead to the symptoms of disease, and to inform strategies that aims to repair damage to myelinated axons for the treatment of human conditions.
Here is just a small sampling of the projects in the lab
The zebrafish is the preeminent vertebrate system for the unbiased discovery of molecular mechanisms underpinning key biological processes. The zebrafish was firmly established as a model following large scale mutagenesis-based gene discovery screens in the 1990's. We have employed mutagenesis-based gene discovery to identify new molecular regulators of myelinated axon biology. In recent years, we have incorporated new technologies (principally those based on the crispr-cas system) that allow rapid and routine generation of mutations in genes of interest to interrogate gene function in a targetted, but still scalable, manner in vivo.
The aquatic existence, small size, rapid development, and availability of transgenic reporters means that one can carry out chemical biology screens to identify compounds that affect various aspects of myelinated axon formation. We have established a platform to carry out fully automated drug discovery screens in zebrafish at high resolution in our UK zebrafish screening facility.
Imaging myelinated axons over time in vivo
We have taken significant time and effort to generate a suite of transgenic reagents that allow us to study many aspects of myelinated axon formation and function over time in the living animal. Please see Publications.