The cytoskeleton in neuronal growth, synapse formation and maintenance
We aim to understand the genetic and molecular mechanisms regulating the cytoskeleton of neurons. The neuronal cytoskeleton (in particular actin and microtubules) drives the migration of neurons, the growth of their axons and dendrites (link) and the formation of synapses (link) during development or regeneration of functional nervous systems. Furthermore, it is essential for the sustained function of the mature nervous system, thus closely relating to neurodegeneration (link). However, the molecular mechanisms underpinning cytoskeletal regulation in neurons remain little understood, since they are complex and experimentally difficult to address. This complexity essentially hampers the advance in our understanding of neurons in health and disease and their responses to drug application.
We experimentally address the complexity of cytoskeletal regulation by using primarily the fruitfly Drosophila which offers numerous advantages for our research (link), and we complement these studies by work in mammalian cell cultures. Through molecular cloning, transgenesis and Drosophila genetics we manipulate and functionally analyse genes down to the level of single amino acids, and study the genetic networks they operate in both in vivo (motorneuronal axons, dendrites, synapses) and in cell culture (primary neurons, heterologous cell lines). These cellular systems are amenable to advanced imaging technologies, electrophysiology, drug application and high-throughput screening approaches.
Current projects focus on cellular mechanisms of axonal growth and synapse formation in health and disease, and aim at roles of the cytoskeleton during neurodegeneration. At the genetic and molecular level, our projects focus on actin-binding proteins (link), microtubule-binding proteins (link), and a class of evolutionarily conserved actin-microtubule linker proteins called spectraplakins which play key roles during neuronal migration, axonal growth, synapse formation and neurodegeneration, but also in wound healing of non-neuronal tissues (link).
For interested student and postdocs, we offer an exciting spectrum of projects ranging from...
- ...axonal growth and synapse formation to neurodegeneration.
- ...cytoskeletal regulators to their upstream signalling systems.
- ...mechanisms in health to those underlying disease.
- ...detailed work on single molecules to large scale screens with robots.
Projects will be carried out in the excellent research environment of the Faculty of Life Sciences in Manchester, providing expertise in a wide range of scientific areas with excellent support through state-of-the-art rese