Super res. imaging (3D-SIM) of actin cytoskeleton in a neuroblastoma cell.
Cells can move and change their shape in part because of a protein called actin, which assembles into organized networks of filaments. Actin networks are dynamic in nature and can be remodeled to change their architecture, allowing the cell to rapidly respond to environmental cues or migrate through complex three-dimensional environments. Actin plays a crucial role in a number of cellular processes, from wound healing to the precise wiring of the neuronal circuitry. My lab studies the regulation of actin during cell motility, neural development, and in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Our approach is largely based on microscopy. We use techniques like super-resolution imaging, photoactivation of fluorescent probes, single molecule imaging, and optogenetics. We also benefit greatly from interaction with computational scientists who help us build mathematical models and extract more quantitative information from microscopy data.
Here are some of the questions that we are currently interested in:
How are actin dynamics regulated by G-actin?
Actin is organized into distinct networks of filaments (F-actin) by recruiting monomers (G-actin) from a large cellular pool. Classically, the G-actin pool has been thought of as homogenous. However, recent work by us and others has shown that actin monomers exist in distinct groups that can be targeted to specific networks, where they drive and modify filament assembly. Disrupting this layer of regulation can cause dramatic changes to cellular behavior. Our projects here are focused on understanding the molecular mechanisms of how G-actin regulates network dynamics and actin-based processes within the cell.
What is the role of actin in motor neuron development and disease?
Motor neurons are the nerve cells that convey information from the brain to the muscles. Recent studies have implied that actin deficiencies may be involved in Amyotrophic lateral sclerosis (ALS), a fatal disease involving motor neuron degeneration. We are using high-resolution microscopy of cultured motor neurons, nerve-muscle explants, ALS mouse models, and induced pluripotent stem cells (iPSCs) of ALS patients to better understand how actin is important to motor neuron physiology and how defects in the regulation of actin can cause motor neuron diseases like ALS.
Funding for our research has been provided by grants from: