Drosophila as a model system to elucidate the molecular mechanisms underlying Amyotrophic Lateral Sclerosis

Description:

What this research means to you: Dr Pennetta’s studies in fruitflies have already shown how mistakes in a gene called VAPB, which is associated with a rare, inherited form of MND, can disrupt the function of motor neurones. This project will again use fruitflies to find out more about how a gene called Sac1 interacts with VAPB and thereby influences the development of MND.

The researcher explains in more detail: Our understanding of what causes MND is still rudimentary. Such poor understanding hinders the development of effective therapies. The main objective of this proposal is to obtain new insights into the causes of ALS by using the fruitfly Drosophila melanogaster, a powerful genetic model that allows us to home in rapidly on molecular mechanisms of disease. Recently, an inherited form of MND has been reported to be due to a mutation in a gene called VAPB. We have shown that in Drosophila, the protein made by this gene is required for the function and the growth of the connections made between motor neurones and muscles. In the past few years our studies in flies have provided the necessary evidence that changing the structure and function of this gene, together with the tendency of the VAPB protein to form aggregates (abnormal protein “clumps”), may underlie the mechanism of at least one form of MND in humans. We have recently identified another gene, Sac1 that interacts with VAPB gene. What role does this new gene play in MND? We will continue to use the power of molecular genetics combined with physiology in flies to answer this question. This experimental approach will rapidly provide a better understanding of the molecular mechanism responsible for MND and will open up the possibility to identify a potential new target for a more effective therapeutic intervention.