Mechanisms of biological macromolecules inspire nanoscale engineering strategies and provide insights into disease.
The speed of genomic sequencing has rapidly increased; opening up 3 billion years of evolutionary engineering, new disease treatment opportunities and providing a perspective on the complex networks involved in most biological processes. Enabled by high throughput approaches, rather than focusing on a single system or pathway I study multiple pathways and processes. I work with the view that in cellular networks there are only a few degrees of separation between the actions of any two molecules. Of particular interest are hub proteins which, through multiple interactions or adopting specific conformations, signal alternate cellular outcomes. By developing an intuition in diverse bio-macromolecular systems I also work on engineering macromolecules for new functions.
Building intuition on the large networks and multi-level feedback loops in cellular systems requires many measurements which current capabilities cannot deliver.
An understanding of mechanism has fallen behind the rate at which new molecules of interest are being identified. I utilize and develop high throughput solution based techniques to characterize the conformations biomolecules adopt in the many contexts they encounter. A primary technique has been small angle X-ray scattering or SAXS. X-rays provide access to high resolution. New light sources provide exponentially increasing power. The two aspects combined provide insights into conformations of a macromolecule in high throughput. I also develop approaches to combine crystallographic results with SAXS. Crystallography is low throughput but provides un-paralleled resolution. SAXS provides access to conformational changes in high throughput.