Clifford Brangwynne

2020 National Award Winner — Faculty

Current Position:
Professor, Chemical and Biological Engineering; HHMI Investigator

Institution:
Princeton University; Howard Hughes Medical Institute

Discipline:
Molecular & Cellular Biology

Recognized for:

Transforming the field of cell biology through a discovery that upends our understanding of the internal organization of cells. Brangwynne discovered that inside cells, biomolecules can merge to form liquid-like droplets that allow for the localization and compartmentalization of molecular interactions. The ability of these droplets to smoothly fuse and separate is critical for cell division and the development of embryos. Errors in this physical property may result in the formation of solid structures, such as the tangles and fibers found in Alzheimer’s disease, which can cause cell damage and death.

Areas of Research Interest and Expertise: Cell Biology, Molecular Biology, Liquid-Liquid Phase Separation, Membrane-less Organelles/Condensates, Biophysics

Previous Positions:

Postdoctoral Researcher, Max Planck Institute for Molecular Cell Biology and Genetics & Max Planck Institute for Physics of Complex Systems, Germany
PhD, Harvard University
BS, Carnegie Mellon University

Research Summary:

Clifford Brangwynne, PhD, has transformed the field of cell and molecular biology through his discovery of what has been called a new state of biological matter. Cell biology textbooks teach us that cells contain separated compartments, called organelles. Organelles, such as mitochondria, are critical for cellular functioning since they concentrate a suite of molecules within a membrane to isolate and promote specific molecular interactions. This type of cellular organization is critical for cellular growth, division, and survival. However, Brangwynne has discovered that membranes are not necessary to sequester and localize biomolecules. Instead, biomolecules can coalesce into liquid-like droplets. These droplets are often referred to as membrane-less organelles or intracellular or biomolecular “condensates”.

Brangwynne’s background in materials science and soft matter physics enabled the discovery and understanding of how these condensates form through liquid-liquid phase separation (LLPS) and how condensates function in cells. LLPS describes the phenomenon in which two mixed liquids separate into distinct phases, such as the separation of oil and water. Intracellular condensates are made up of biomolecules that have properties that enable them to coalesce like liquid droplets with the ability to dynamically fuse and separate. Membrane-less condensates represent the merging of hundreds of biomolecules such as proteins and RNA to form one of these droplets, promote localized molecular interactions, and then separate to engage in a different set of localized molecular interactions. These types of rapid, dynamic molecular changes are critical for cell division and the development of embryos.

Since Brangwynne’s discovery of intracellular LLPS, labs throughout the world have discovered new types of membrane-less condensates, as well as the repercussions of related pathological phase transitions. Improper phase separation can lead to neurodegenerative diseases. For example, when biomolecules within these droplets are unable to separate they can form stiff fibers and tangles that cause neuronal damage found in Alzheimer’s disease.

It’s a tremendous honor to be chosen as a Blavatnik National Awards Laureate. The recognition of this new field at the interface of cell biology and soft matter physics inspires my lab to continue breaking the barriers separating scientific disciplines.

Key Publications:

S. Elbaum-Garfinkle, Y. Kim, K. Szczepaniak, C.C. Chen, C.R. Eckmann, S. Myong, C.P. Brangwynne. The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics.Proceedings of the National Academy of Sciences, 2015.

M. Feric, N. Vaidya, T.S. Harmon, D.M. Mitrea, L. Zhu, T.M. Richardson, R.W. Kriwacki, R.V. Pappu, C.P. Brangwynne. Coexisting liquid phases underlie nucleolar subcompartments.Cell , 2016.

Y. Shin, C.P. Brangwynne. Liquid phase condensation in cell physiology and disease. Science , 2017.

Y. Shin, Y-C. Chang, D.S.W. Lee, J. Berry, D.W. Sanders, P. Ronceray, N.S. Wingreen, M.P. Haataja, C.P. Brangwynne. Liquid nuclear condensates mechanically sense and restructure the genome. Cell, 2018.

Other Honors:

In the Media:

Nature Methods - Cell biology befriends soft matter physics

Scientific American – “Lava Lamp” proteins may help cells cheat death

Nature – Cell biology’s new phase: What lava lamps and vinaigrette can teach us about cell biology

The Scientist – These organelles have no membranes

Nature Reviews in Drug Discovery – Biomolecular condensates pique drug discovery curiosity

Nature Methods – Optogenetic tools light up phase separation

Journal of Cell Biology – Cliff Brangwynne: All the right materials

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