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Theme 2 colloquium: ""Model systems for membraneless subcellular organelles: Compartmentalization of biomolecules and reactions by liquid-liquid phase coexistence" (Lecture)

Wednesday 25 January 2017Add to my calendar
from 16:00
Prof. Chris Keating (Penn State Department of Chemistry, University Park, USA)

Christine Keating USA jan2017The inside of biological cells is organized into numerous subcellular compartments, many of which lack the membrane boundaries that define better-known organelles such as mitochondria. Membraneless organelles are biomacromolecule-rich liquid droplets that can provide privileged reaction environments and are thought to serve important roles in RNA processing, stress response, and other functions. These structures are often dynamic, appearing and disappearing at different times in the cell cycle or in response to cellular stress. We are studying mechanisms for, and consequences of, this type of dynamic intracellular compartmentalization using a variety of simple model systems composed of phase-separating aqueous polymer solutions. Model polymer systems include polyethylene glycol/dextran, RNA/peptide, and polyamine/ADP, all of which undergo liquid-liquid phase separation in water. These simple systems allow us to test hypotheses for droplet formation/dissolution mechanisms, explore droplet-membrane interactions, and evaluate the extent of compartmentalization and its consequences for biochemical reaction kinetics.

Through these types of studies, we hope to uncover underlying physiochemical mechanisms in cellular organization and to identify new avenues for biomimetic systems for applications in biotechnology and materials science. For example, compartmentalization of catalysts and/or reactants into polymer-rich droplets can lead to control over the sites and rates of reactions. We have used this approach to increase ribozyme reaction rates and to develop liposome-stabilized water-in-water emulsions that act as artificial mineralizing vesicles. An additional focus has been developing coacervate systems that can reversibly compartmentalize biomolecules in response to a biochemical stimulus. For example, in RNA/cationic peptide systems, phase transitions can be induced by changes in peptide phosphorylation state, leading to the capture or release of biomolecular solutes such as proteins or nucleic acids.