Inter-organelle communication through membrane contact sites in oncology and neurodegenerative diseases (InterAction)

‘Membrane contact sites’ (MCSs) between organelles within a eukaryotic cell provide structural integrity and promote organelle homeostasis by facilitating intracellular signalling, exchange of metabolites, lipid metabolism and membrane dynamics. Cataloguing MCSs revolutionized our understanding of the structural organization of a eukaryotic cell, but the functional role of MCSs is only gradually emerging. Moreover, alterations of the molecular composition of MCSs, affecting organellar tethering and MCS’s signaling functions, are increasingly recognized to contribute to the etiopathology of neurodegenerative diseases and cancer. This is supported by exciting preliminary insights from our consortium with a strong expertise and focus on common pathways and disease-associated proteins with emerging functions at MCSs in cancer and neurodegeneration. Within the relevant and rapidly evolving field of MCS research, we propose the project InterAction, aiming to extend powerful insights on the composition and function of MCSs in key model organisms as yeast, and to investigate the role of MCSs in the human disease context of cancer and neurodegeneration. By combining state-of-the-art research tools, complementary expertise on major disease-associated proteins, and a broad range of models including yeast, clonal cells and human neurons, we will establish a cutting-edge MCS expertise platform. We will compare MSC functionality in normal cells and in disease models of cancer and neurodegeneration by focusing on the regulation of MCSs, their role in nutrient sensing, ion exchange, and lipid metabolism, distribution and transport.

Keywords:Vacuolar/lysosomal and mitochondrial fun, Cell death, Interactomics, Proteomics, Super-resolution imaging, Yeast, iPSCs, Human differentiated neurons, Cancer cells, Stroma cells, Inter-organelle lipid transport/transfer, Inter-organelle ion exchange

Disciplines:Intracellular compartments and transport, Cancer biology, Neurological and neuromuscular diseases