Our overarching goal is to discover the physical principles underlying spatial and temporal organization of proteins and nucleic acids within cells and to understand how mis-regulation of protein phase separation and aggregation give rise to neurodegenerative diseases such as Huntington’s disease and ALS. Conceptually, we are interested in the physics of living systems that connects information encoded in molecular matter via spontaneous and driven processes to understand how information encoding gives rise to mesoscale control that leads to a living cell. Specific foci include the form and functions of intrinsically disordered proteins, biomolecular phase transitions, and the principles of molecular recognition. Our discoveries are driven by development, adaptation, and deployment of theoretical, computational, and experimental tools from the fields of polymer physics, equilibrium and non-equilibrium statistical physics, biochemistry, and molecular engineering. We wear two hats - those of biophysicists and of engineers. And as engineers, we leverage fundamental insights to pave the way for finding cures for neurodegenerative disorders and pursue applications in materials science and synthetic biology.
PIMMS based simulations showing the organization of disordered low complexity domains within a phase separated droplet
(Courtesy of Dr. Alex S. Holehouse)
Our overarching goal is to discover the physical principles underlying spatial and temporal organization of proteins and nucleic acids within cells and to understand how mis-regulation of protein phase separation and aggregation give rise to neurodegenerative diseases such as Huntington’s disease and ALS. Conceptually, we are interested in the physics of living systems that connects information encoded in molecular matter via spontaneous and driven processes to understand how information encoding gives rise to mesoscale control that leads to a living cell. Specific foci include the form and functions of intrinsically disordered proteins, biomolecular phase transitions, and the principles of molecular recognition. Our discoveries are driven by development, adaptation, and deployment of theoretical, computational, and experimental tools from the fields of polymer physics, equilibrium and non-equilibrium statistical physics, biochemistry, and molecular engineering. We wear two hats - those of biophysicists and of engineers. And as engineers, we leverage fundamental insights to pave the way for finding cures for neurodegenerative disorders and pursue applications in materials science and synthetic biology.
Relevant diseases: Huntington's disease; Alzheimer's disease; Parkinson’s disease; ALS; Cancers.
Processes of Interest: Self-Assembly via homotypic interactions; Phase Transitions of multi-macromolecular systems; Functions via conformational heterogeneity; Proteostasis; Nuclear Transport; Prion-like propagation of aggregates.
Techniques used: Atomistic and mesoscopic computer simulations; Polymer physics theories; Modeling hierarchical networks; Bioinformatics; In vitro and in cell biophysical experiments.
Funding: We currently receive funding from the Air Force Office of Scientific Research (AFOSR), St. Jude Children’s Research Hospital, and the National Institute for Neuronal Disorders and Stroke (NIH-NINDS). Key personnel who work with us and help with collaborative efforts are supported by the Center for Biomolecular Condensates within the James McKelvey School of Engineering at WashU.
Last updated: March 27th, 2023
