(MURI-20) UNCOVERING AND APPLYING THE INTERFACIAL DESIGN PRINCIPLES OF MULTIPHASIC NATURAL AND SYNTHETIC ORGANELLES
Abstract
Recent discoveries have shed light on the way in which phase transitions within living cells driveself-assembly of membraneless organelles, also known as biomolecular condensates, raising the possibility for harnessing this fundamental physical driving force for engineering synthetic organelles. However, the way in which protein sequence encodes the biophysical properties of condensates, in particular features of their surfaces, remain uncharacterized and poorly understood, presenting a major obstacle to such efforts. In this project, we bring together leading experts in cell biology, biophysics, computational modelling, and bioengineering to probe endogenous phase separated condensates, and build from this knowledge to engineer synthetic condensates, to address previously intractable challenges in natural product biosynthesis. Efforts bridging experiments in living cells, as well as model in vitro condensates, and engineered in vitro and intracellular synthetic organelles, combined with advanced computational modelling of protein-sequence dependent phase behavior, will break new ground in this nascent field. Organelles are involved in nearly all aspects of cell physiology and disease, and achieving our goal of building custom, self-assembling organelles will have a major impact on the DoD biomedical research portfolio, including areas ranging from neurodegenerative disease to bioterror remediation.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 12, 2021
- Source ID
- FA95502010241
Entities
People
- Clifford P. Brangwynne
Organizations
- Air Force Office of Scientific Research
- Trustees of Princeton University
- United States Air Force