Robin Klemm - Development & Cell Biology - 'How the shape and metabolic function of mitochondria control cellular specialization in differentiation'

Mitochondria are best known for their role in energy metabolism but have recently emerged as critical signalling hubs which are important during cellular differentiation from stem cells. Metabolic adaptability is crucial in decision making processes called “fate switches”. The machinery which controls these processes is beginning to emerge but many central questions remain unanswered. We have recently discovered that mitochondrial contact sites with other organelles in the cell are critical in regulating these processes. The contact site factors establish physical interactions with e.g. the endoplasmic reticulum and specialize in importing specific lipids that remodel the shape, function and biochemical activity of mitochondria. These changes in turn determine the fate of the cell and control mechanism that establish new cellular identity. This PhD project will use CRISPR-genetics in combination with fluorescence microscopy and easy to study metabolic readouts to discover the cell biological mechanisms by which mitochondria remodel their function. We focus on a mitochondrial contact site protein, which, according to its phosphorylation status can interact with different organelles in the cell. The selection of preferred binding partners within the mitochondrial neighbourhood has profound consequences on mitochondrial function and cell fate. We have evidence from mass spectrometry experiments that mitochondrial import of specific lipids modulates the mitochondrial function depending on which other organelle is bound. How cell biological mechanisms organize organelle neighbourhoods and inter-organelle communication is an exciting new area in the molecular life sciences and has relevance in all cell-types which are metabolically active such as fat cells, liver, neurons and muscles.