Functions of Heparan Sulphate in the C. elegans Nervous System

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My research is aimed at understanding the development of the nervous system at the molecular level. I am particularly interested in a group of complex glycoproteins, heparan sulphate proteoglycans (HSPGs). My research uses the nematode Caenorhabditis elegans as a simplistic genetic model. Understanding neuronal development is one of the fundamental questions in biology as neurons control actions from movement to autonomous functions such as heart beat and breathing, and our ability to sense, think and remember. The adult human brain has over hundred billion neurons which each make connections with an average of 1000 target cells, yet mistakes happen very rarely. Neuron migration and formation of neuronal connections during development are genetically determined and dictate the wiring of the entire nervous system, yet the molecular mechanisms are still poorly understood. HSPGs are present in cell membranes and in the extracellular space between cells. HSPGs mediate interactions of cells with their environment and play critical roles in regulating development and homeostasis. In the nervous system HSPGs guide migrating neurons and their processes, and control functions involved in learning and memory. C. elegans contains homologues of key genes involved in human neuronal development. A simplified model is expected to improve understanding of HSPGs in normal cellular communication. Understanding normal development will provide novel insights into mechanisms that underlie cancer, degenerative neuronal diseases such as Alzheimer’s and Parkinson’s, and regeneration after injury.