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Salt-dependent rheology and surface tension of protein condensates using optical tweezers // Modeling FUS amyotrophic lateral sclerosis using iPSC reporter lines

CMCB Postdoc seminar

Datum:18.05.2018, 16:00 - 17:00
Sprecher: Elisabeth Fischer-Friedrich // Jared Sterneckert, Lara Marrone (Predoc)
Ort: CRTD, auditorium left

Abstract 1st talk

An increasing number of proteins with intrinsically disordered domains have been shown to phase separate in buffer to form liquid-like phases. These protein condensates serve as simple models for the investigation of the more complex membrane-less organelles in cells. To understand the function of such proteins in cells, the material properties of the condensates they form are important. However these material properties are not well understood. Here, we develop a novel method based on optical tweezers to study the frequency-dependent rheology and surface tension of PGL-3 condensates as a function of salt concentration. We find that PGL-3 droplets are predominantly viscous but also exhibit elastic properties. As the salt concentration is reduced, their elastic modulus, viscosity and surface tension increase. Our findings show that salt concentration has a strong influence on the rheology and dynamics of protein condensates suggesting an important role of electrostatic interactions for their material properties.

Abstract 2nd talk

Modeling FUS amyotrophic lateral sclerosis using iPSC reporter lines Neurodegenerative diseases are affecting an increasing number of people, but, despite many attempts, there are almost no successful drugs. Amyotrophic lateral sclerosis (ALS) is a particularly devastating disease in which very many pathways, targets, and drug candidates have been identified, yet only two drugs exist - and these drugs only extend life by a few months. We propose a critical reason that this translational gap exists has been that the cells that are most affected - motor neurons - have not been available for study. Induced pluripotent stem cells (iPSCs) offer a breakthrough technology in which theoretically limitless numbers of these cells can be generated and used to replay the disease process and discover effective drugs. Using mutant FUS as an example, we generated novel reporter lines and generated a new disease model in which stress granules play a critical role. Using this model, we identified a new therapeutic target - autophagy - and we discovered FDA-approved drugs that can be repurposed to treat ALS patients.

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