Clive Wilson - Metabolism & Endocrinology - 'Regulation of microcarriers: new messengers of cell-cell and reproductive signalling in higher organisms'

Cell-cell communication controls almost all physiological processes in multicellular organisms and is defective in many diseases. Our group has developed the male reproductive accessory gland in the fruit fly Drosophila melanogaster as a new genetic model to study the fundamental processes involved in secretion and signalling. Employing this system, we discovered that multiple secreted signals, including Sex Peptide, the central regulator of female post-mating responses, are packaged into lipophilic structures that we call microcarriers, which stabilise these proteins in the gland and then permit their rapid release when deposited in the female uterus. We have now found that evolutionarily conserved derivatives of the lipid ceramide and the enzymes that produce them have multiple roles in generating microcarriers. In humans, components of this microcarrier biogenesis pathway are required for several biological processes in humans. They are highly upregulated in cancer and implicated in metabolic disease and obesity. In this project, additional new evolutionarily conserved regulators of microcarriers that we have recently identified will be characterised using advanced genetic and imaging technologies to determine their functions. We anticipate that this work could provide the stepping stone to extend our studies into human cells and assess the relevance of microcarriers to human health and disease.