Asymmetric Inheritance of a Regulatory Memory by Organelle Tethering

Type of Award: Catalyst
Date Awarded: August 2016
Award End Date: July 2018
Amount Awarded: $ 250,000.00
PI(s): D. Allan Drummond, PhD, UChicago; Laura Lackner, PhD, NU;

Abstract: Stresses such as heat and oxidation cause protein aggregates to form in cells. In assymetrically dividing cells, aggregates containing misfiled proteins are preferentially retained in older cells by becoming tethered to organelles: mitochondria and the endoplasmic reticulum (ER). This has been interpreted as reducing transmission of irreversibly damaged proteins to young cells, which would rejuvenate the cell lineage each generation. Yet, this interpretation is based on studies of foreign proteins, and is challenged by the recent systems-level work in the Drummond lab demonstrating the reversibility of most endogenous stress-induced aggregates, suggesting an alternative regulatory interpretation. By joining forces with the Lackner lab, which has deep expertise in mitochondrial and ER tethering, we propose as integrated biochemical and imaging study of tether-mediated asymmetric aggregate retention. This new collaboration will bring powerful new methods to bear on the fundamental question of how cells selectively transmit information about past events to offspring.