What interests us and why?

The overarching scientific question we are interested in is: how do biophysical properties of microtubules and their modifiers produce cell morphology and organismal physiology?

Microtubules are essential polymers rigid enough to serve as the cell’s structural scaffold - as rigid, in fact as Plexiglas - but dynamic enough to produce the changes in shape we see during cell division, migration and tissue growth. How do they achieve this dual nature? How do they deliver organelles and other cell components to precise locations at the farthest reaches of the cell, and then reorient to deliver those components to new locales to accommodate the changing requirements of cell physiology?  In no other cell type is this requirement more onerous than in the neuron where a large microtubule mass needs to be generated during axonal growth and cargo needs to be transported over distances several thousands of times the diameter of the cell body.

We can think of the complex behavior of the microtubule network as a function of several “unit operations”, i.e. the individual actions of cytoskeletal regulators: nucleation, growth and shrinkage, severing and motor movement. Many human diseases, including neurodegenerative disorders, cancers, cardiovascular disease, fungal, bacterial and viral infections, are due to mutations in genes that encode microtubule dynamics regulators. Our goal is to understand the biophysical parameters of these unit operations that are the kernel of cytoskeleton structure and function, as well as their perturbations in disease states.

What approaches do we use?

X-ray crystallography	SAXS	EM	Protein Engineering	Single Molecule Fluorescence	Live Cell Imaging

We take a multifaceted experimental approach, linking atomic resolution information on cytoskeletal regulators with single molecule dynamics in vitro and the larger context of the cell. We combine X-ray crystallography, small angle X-ray scattering (SAXS) and electron microscopy (EM) to obtain an atomic resolution snapshot of these tiny protein machines. Classical kinetics as well as high-resolution fluorescence microscopy and spectroscopy techniques are employed to understand the dynamic behavior of these molecular machines and the knowledge of their fundamental properties garnered from these in vitro studies is used at the cellular level.

Who does the research?

The lab welcomes biologists, chemists, physicists and engineers who are interested in joining our interdisciplinary efforts to study these fascinating biological polymers and the proteins that regulate them.