News & Events

When

Date - April 10, 2015
1:00 pm - 2:00 pm

What

Biological Sciences Division
Pacific Northwest National Laboratory

“Chemical Probing to Investigate Human Phase I Metabolism and Microbial Protein Functions and Regulation”

Abstract:

We have a keen interest in using chemical biology to understand protein functions, interactions, and regulatory processes in living microbial systems and in mammalian metabolism. To interrogate key questions within these realms we use organic chemistry to synthesize chemical probes that are then deployed in living systems. Characterization of probe targets is then performed by proteomics, high-resolution fluorescence microscopy, flow cytometry and other techniques.  A primary focus of ours is on the dynamic reversible reduction and oxidation of protein cysteine thiols, which we believe to be a particularly important means of regulating protein function. We have probed the cyanobacterium, Cyanothece sp. 51142, to understand how redox dynamics influence protein function and concomitant production of hydrogen. A second major effort is on the identification of transporters and proteins associated with nutrient acquisition and metabolism in microbes and phototrophic microbial mats. Probes have been used with proteomics and structured illumination microscopy to characterize spatiotemporal uptake and distribution of B vitamins in microbial communities. We believe our emerging chemical probe technology coupled to proteomics and microscopy provides unparalleled ‘views’ into microbes and microbial communities based upon cellular functions.  In addition to our microbial studies we are also exploring the role metabolic disease plays in altering lung and liver metabolism. Two of the most important risk factors for human morbidity and mortality are exposure to cigarette smoke and obesity, both of which are associated with chronic inflammation, oxidative stress, and diseases such as type 2 diabetes mellitus and cancer. We have used activity-based protein profiling to evaluate the concomitant effects upon cytochrome P450 enzyme activity of tobacco smoke exposure and obesity.