The cytoplasm is a mysterious jelly-like substance that sustains the biochemical reactions that are essential for life. How the cytoplasm organizes itself is one of the big remaining questions in biology. We use cell biological, biochemical, biophysical and genetic approaches and diverse model systems, such as yeast, Dictyostelium, and mammalian cells, to elucidate the molecular principles underlying the organization of the cytoplasm. We are particularly interested in understanding how the cytoplasm reorganizes itself upon environmental perturbations and stress. Stressed cells undergo changes on many levels to alter their physiology and metabolism; we are beginning to understand that many of these changes result from alterations in the structure and organization of the cytoplasm.
Our recent work shows that stressed cells form many membraneless compartments in the cytoplasm via a biophysical process known as phase separation. However, the initially beneficial ability to form compartments becomes detrimental with increasing age, because compartment-forming have a tendency to misfold and aggregate and thus are closely tied to aging and the pathogenesis associated with age-related diseases such as amyotrophic lateral sclerosis (ALS). Thus, recent efforts in the lab are focused on understanding the molecular links between membraneless compartments and age-related diseases.
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