Avinash Patel
Max Planck Institute of Molecular Cell Biology and Genetics, Germany
Title: Dissecting the mechanisms of liquid to solid phase transition associated with neurodegenerative diseases
Biography
Biography: Avinash Patel
Abstract
FUS/TLS is a prion-like protein that contains intrinsically disordered domains and is associated with neurodegenerative disease. We recently showed that intracellular FUS/TLS compartments form under various cellular conditions and that these compartments exhibit liquid-like properties in vivo and in vitro. “Aging” experiments revealed that FUS/TLS liquid droplets undergo a phase transition to a solid-like state which is accelerated by disease mutations. We discovered that concentrating proteins by phase separation comes with the trade-off that can also promote protein aggregation. Solid-like aggregates of prion-like proteins are a hallmark of many aging-associated diseases. Aberrant phase transitions might be one trigger causing aging-associated diseases. However, the molecular mechanisms underlying this aberrant phase transition and the strategies cells have developed to sustain the function of these aggregation-prone proteins remain largely enigmatic. Here, we present recent advances we made in understanding the mechanisms cells might have developed to prevent the liquid-solid phase transitions by using a wide range of biochemical, biophysical and cell biology techniques. We find that electrolytes, small compounds and protein interactors affect the liquid-liquid, as well as liquid-solid transitions. Insights gained from studying liquid-solid phase transition might help us developing drugs targeted to treat age-associated diseases.
