My research focuses on a broad range of topics ranging from protein folding, oligomerization of proteins in neurodegenerative diseases, microfluidic device design and fabrication.  I also collaborate with a number of groups (see Collaborations).  My research also often involves the development of custom instrumentation.  These can be viewed under Instrumentation.

Protein folding

Proteins are known to adopt specific (but dynamic) three-dimensional structures that allow them to carry out their function.  It is well recognized that this process doesn’t occur by a random search but is instead a biased search.  We are interested in understanding the factors that guide the protein to the correct structure or set of structures.

Live cell imaging

Live cell microscopy: The other question that we are interested in addressing focuses on understanding the factors leading to toxicity in live cells.  To this end. we have built a 2-photon (also capable of 1-photon confocal) laser scanning microscope custom suited for long-time live cell studies.  The goal is to track the spatial localization and oligomerization of SOD1 in live cells and correlate that with toxicity.

SOD1 single-molecule trace

Single-molecule fluorescence and FCS

Another area that we are interested in is using single-molecule fluorescence methods for studying protein folding reactions, protein-protein interactions and protein oligomer formation.  Single-molecule methods can be used to probe protein oligomer formation and also, using fluorescence correlation spectroscopy, probe dynamics from the sub-microsecond to tens of seconds timescale.  To enable these studies we have built

Oligomerization mechanism of SOD1

Another part of this study is focused on identifying the small oligomers present and the regions of SOD1 involved in stabilizing these small oligomers.  We are pursuing these studies by a number of biophysical tools, including hydrogen exchange mass spec and fast photochemical oxidation (in collaboration with Michael Gross’ lab at Washington University in St. Louis), single-molecule methods and electron microscopy.