We aim to understand the fundamental molecular and cellular mechanisms underpinning vertebrate nervous system formation, function and repair.
Our Specific aims
Our current focus is on understanding how myelinated axons are built in our nervous systems. Myelinated axons are essential for normal nervous system development and function, and disruption of the myelin sheath and associated axons is associated with many human diseases including Multiple Sclerosis (MS). We currently have a poor understanding of the fundamental mechanisms that control myelinated axon formation in the living animal, which impedes goals to repair their damage in disease or following injury. Our goal is to bridge these gaps in our knowledge and help accelerate development of treatments to promote nervous system repair.
Here's just a small sampling of the projects in the lab
Forward Genetic screening
We use classical three generation forward genetic screens to identify the molecular basis of myelinated axon formation. Mutations are induced at random, bred to homozygosity, whereupon the F3 progeny of Families of F2 fish (as shown above) are screened for interesting phenotypes. Given that mutations are induced at random, once phenotypes are identified their molecular identity must be established, e.g. by whole genome sequencing approaches. In this way we gain new insight into the genetic basis of myelinated axon formation.
Chemical Biology Screening
The aquatic existence, small size, rapid development, and availability of transgenic reporters means that we can carry out chemical biology screens to identify compounds that affect various aspects of myelinated axon formation. We are currently introducing technologies to automate these screens, more details of which will follow soon.
How InDIVIdual OLIgodendrocytes generate myelin sheaths
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 that have remained unexamined in the past, including simply investigating how it is that the myelinating glial cell of the central nervous system, the oligodendrocyte, generates its myelin sheaths in vivo. Please enjoy our movie and image gallery, which will be expanded soon.