Assistant Professor Shashank Shekhar has received the National Science Foundation’s prestigious CAREER Award, with $1.2 million in funding over five years to support research and education initiatives focused on actin cytoskeleton dynamics. The CAREER Award will support his lab’s research investigating a newly discovered mechanism of actin filament growth that challenges a decades-old paradigm in cell biology. For over forty years, actin filaments were thought to grow almost exclusively from one end, known as the barbed end. His lab has recently identified two proteins, the bacterial protein VopF and mammalian Leiomodin (Lmod), among the first known proteins capable of driving processive actin filament growth from the opposite, pointed end. This project will define the molecular mechanisms underlying pointed-end actin polymerization using an interdisciplinary approach that combines single-molecule biophysics, protein biochemistry, live-cell imaging, and mathematical modeling. The research aims to uncover new principles of cytoskeletal regulation and identify previously unknown mammalian proteins that regulate pointed-end growth. In addition to tackling fundamental questions in cytoskeletal biology, the award will also support educational initiatives that train students at the interface of biology, physics, and chemistry through interdisciplinary research, outreach activities, and new quantitative biology courses at Emory.
Additionally, Prof. Shekhar secured a $2.3M NIH MIRA renewal for his research on actin dynamics. This will support the next phase of his research program on the mechanochemical regulation of actin filament dynamics. The five-year renewal reflects continued NIH support for Dr. Shekhar’s innovative research aimed at understanding how biochemical and mechanical signals are integrated to regulate actin filaments – essential components of cells that drive key processes such as cell migration, wound healing, cell division, and force generation. Recent discoveries from Dr. Shekhar’s lab have challenged long-standing models of actin dynamics by uncovering unexpected mechanisms governing filament growth and disassembly at both ends of actin filaments. Building on these discoveries, the MIRA-funded project will investigate how multiple actin regulatory proteins work together to generate emergent behaviors and how mechanical forces influence these interactions at the molecular level. By combining single-molecule biophysics, microfluidics-assisted imaging, structural analysis, and modeling, this work seeks to reveal fundamental principles governing cytoskeletal remodeling in living cells. The findings may ultimately inform therapeutic strategies for diseases linked to defective actin regulation, including metastatic cancer and neurological disorders.