Lipid mediated organelle-crosstalk controls cell-fate and function

Mitochondria are dynamic organelles that play an essential role in determining the functions of the cell-types in the human body. Remodelling of the lipid composition of mitochondrial membranes is a key regulator of cellular specialisation. Despite the vital importance in health and disease the mechanisms underpinning these processes remain largely unknown. I propose to systematically investigate the mechanisms that reprogram mitochondrial function through lipids. We will focus on selective lipid transport between organelles at membrane contact sites. I hypothesise that mitochondria interact with specific partner organelles to control the selective import of lipids. The defined mitochondrial lipid composition governs mitochondrial activities and thereby cell function. Using candidate approaches and unbiased ‘omics discovery strategies, we aim at defining the complete machinery around mitochondrial contact-sites and will elucidate how the system remodels the mitochondrial lipid composition during nutrient stress and differentiation. Combining CRISPR-knockout, AI-enhanced imaging and metabolic assays, we will unravel the mechanisms by which cells control and exploit mitochondrial lipid composition to determine cell-fate. Taken together my research programme will open a novel perspective on fundamental cell-biological processes in the regulation of physiological metabolism, which may lead to new treatments of a wide spectrum of metabolic and genetic disorders.