Molecular basis of phase separation in viral replication and neurodegenerative disease

Cells are organised into compartments, including membrane-bound organelles, e.g. nucleus/mitochondria, or membrane-less organelles, formed form by phase separation (akin to oily droplets that form in water). In certain neurodegenerative diseases, such as motor neuron disease and dementia, proteins normally found in membrane-less organelles form toxic deposits. Also, when viruses invade cells, membrane-less organelles form where viral replication occurs. Despite the importance of membrane-less organelles in disease and infection, we still don’t understand how they form. I will make new discoveries about the structures of the proteins that form membrane-less organelles by studying a model protein, TDP-43, which plays a role in in neurodegeneration, and proteins that form viral replication organelles in Rotavirus-infected cells. Rotaviruses, a common cause of gastrointestinal infections, are responsible for more than 200,000 child deaths annually. The understanding of membrane-less organelle formation afforded by these studies may lead to new treatments for neurodegenerative disease and viral infection.