LAUSR

I guess I am a little unusual in cell biology in that I am still studying the same thing that I studied as an undergraduate at King's College in the University of London more than 40 years ago. One of my lecturers invited me to do research in his lab. His work focused on neurofilaments, which are the intermediate filaments of nerve cells. They are long, flexible, rope-like cytoskeletal polymers that fulfill structural roles in axons. Fast forward four decades, and I am still working on neurofilaments. Over the years we have built up a significant body of knowledge about these structures and they keep surprising us. It is these surprises that have sustained my interest. For example, we discovered that these structural polymers are also cargoes of axonal transport, unique among known cargoes of intracellular transport in that they are long flexible protein polymers. The filaments can engage with molecular motors and move bidirectionally along microtubule tracks. Key questions in my lab are, what is the mechanism of the movement, how is it regulated, and what is its function? More recently, we have also become interested in the role of neurofilaments in disease. In particular, we are studying a neurodegenerative disease called Charcot-Marie-Tooth disease Type 2E (CMT2E). CMT2E is a peripheral neuropathy caused by mutations in one of the neurofilament subunit proteins. We are working with mouse models of this disease and aim to develop a viral gene therapy for rescuing the disease.