Gregory Alushin
Rockefeller University, NY·Biophysics
Cells constantly feel the physical world around them: how stiff a surface is, how fluid flows past them, how hard neighboring cells pull. Those mechanical cues must be translated into chemical messages inside the cell that change its behavior and switch genes on or off.
- Fields
Biophysics
Biochemistry
Biology
- Topics
mechanotransduction
actin cytoskeleton
F-actin
- Grants
- 2 known grants, through Feb 2031
What they work on
- Determine the structural mechanisms and cellular functions of catch bonds, protein contacts that strengthen under pulling force, in cytoskeletal crosslinking proteins and cell adhesion proteins implicated in force sensing.
- Define how LIM domain proteins recognize actin filaments under tension, examining single filaments and higher-order networks in vitro and in cells with cryo-electron microscopy and cryo-electron tomography.
- Test how zyxin, a LIM protein that binds tensed actin, directs repair of physical damage to actin-myosin cables, using cell assays and reconstitution with purified proteins.
- Investigate how FHL1 and FHL2, Four-and-a-Half LIM domain proteins, move into the nucleus in response to matrix stiffness and regulate gene expression there.
- Visualize force-activated binding of LIM proteins to actin filaments at near-atomic detail by cryo-electron microscopy, to test whether distinct force-induced filament states are read by distinct proteins.
More about the research
This translation process, called mechanotransduction, is essential for normal development and tissue maintenance, and it goes wrong in diseases including cancer, fibrosis and muscular dystrophies. Yet compared with chemical signaling, we know little about how a physical force actually changes a protein so it sends a signal. Work in this lab focuses on the actin cytoskeleton, the cell's internal scaffold of filaments and motor proteins, and asks how force reshapes these proteins to carry information.
Why it matters
Faulty cellular force-sensing is associated with muscular dystrophies, fibrosis and cancer. By defining how forces physically reshape cytoskeletal proteins to produce chemical signals, this work could identify specific molecular steps that distinguish one mechanical signaling pathway from another, which may eventually guide chemical probes or drugs that target mechanotransduction selectively rather than disrupting the cytoskeleton as a whole.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
E. Ostap
University of Pennsylvania, PA·Biophysics
Determine the structural basis of myosin force sensing by testing conserved residues that tune tension sensitivity in Myo1b and Myo1c, using engineered motors, microsecond optical trapping and cryo-EM.
Willy Wriggers
Old Dominion University, VA·Biophysics
Develop measures of how well an atomic model fits local regions of a cryo-electron microscopy (cryo-EM) density map, and rate maps against reliable reference structures.
Maria Lara-Tejero
Yale University, CT·Microbiology & Immunology
Determine the structure of the Salmonella type III secretion sorting platform, the part of the injectisome inside the bacterium, using cryo-EM and cryo-electron tomography.
The school
Rockefeller University: 6 labs on PI Pages, $305M a year on research, 38 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.