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A Concentration-Dependent Liquid Phase Separation Can Cause Toxicity upon Increased Protein Expression

Event Details:

  • Date: - -
  • Venue: Aula A, Unit of Biochemistry, 3/B via Taramelli, Pavia
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On Thursday the  8th 2016 at 3.00 pm Dr B Bolognesi of the Centre for Genomic Regulation in Barcelona will give a seminar entitled A Concentration-Dependent Liquid Phase Separation Can Cause Toxicity upon Increased Protein Expression in the Unit of Biochemistry (Aula A). All members of the Department and other interested participants are invited to attend.

Abstract. Multiple human diseases are associated with a liquid-to-solid phase transition resulting in the formation of amyloid fibers or protein aggregates. Here, we present an alternative mechanism for cellular toxicity based on a concentration-dependent liquid-liquid demixing. Analyzing proteins that are toxic when their concentration is increased reveals that they share physicochemical properties with proteins that participate in physiological liquid- liquid demixing in the cell. Increasing the concentration of one of these proteins indeed results in the formation of cytoplasmic granules with liquid properties. Demixing titrates proteins and mRNAs from the cytoplasm, resulting in toxicity. Granule formation is reversible, and resumption of growth occurs as the granules dissolve when protein concentration falls. Preventing liquid demixing abolishes the dosage sensitivity of the protein. Triggering inappropriate liquid phase separation may be an important cause of dosage sensitivity and a determinant of human disease.

Reference. Bolognesi B et al. A Concentration-Dependent Liquid Phase Separation Can Cause Toxicity upon Increased Protein Expression. Cell Reports 16:222-31 (2016)

Biography.  Benedetta Bolognesi graduated from the Univeristy of Pavia with an MSc in Biotechnology. She then joined Chris Dobson Group at the University of Cambridge where she was funded by the Alzehimer’s Research Trust to conduct her PhD studies. Her doctoral work focused on the Amyloid Beta peptide and the biophysical properties of its aggregation. Following her PhD, she joined the CRG in Barcelona thanks to a Marie Curie Interdisciplinary fellowship. She developed a joint project between Ben Lehner’s and Gian Tartaglia’s lab, focusing on the relationship between gene dosage and protein aggregation.

 

 

 

 

 

 

 

 

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