U.S. Department of Energy

Pacific Northwest National Laboratory

Chemical Proteomics

One of the most pressing needs in 21st century biology is to understand the functions of proteins and the pathways they use to regulate function in cells and other organisms.

Proteins are the worker bees of all living systems. They are in charge of DNA replication, enzymatic reactions for metabolism, molecular transport, and more. At any given moment, an organism contains a set of proteins that are turned on, or “expressed,” in ways that determine that organism’s function.

Considered together, proteins can be studied as a functional “proteome” – that is, the entire set of expressed proteins at work at any one time. Taking this yet another step further, the study of chemical proteomics provides approaches for improved understanding of the functional proteome and how it is regulated. This research requires devising ways to detect modifications, activities, and functions of proteins.

Our chemical biology research team is highly collaborative and diverse—a composite of biologists, chemists, and chemical biologists. Our team strengths include synthetic organic chemistry for probe development, chemoproteomics, and environmental and human health biology. 

 

Our methods

We develop and deploy active-site, modification-directed, or metabolite-based chemical probes that form irreversible bonds to protein targets in microbes, microbial communities, and mammalian cells and tissues. These chemical probes adhere to living biological systems or cellular extracts. Then they append enrichment moieties or fluorescent groups via click chemistry for subsequent imaging characterization. This results in an improved functional and mechanistic understanding of biological processes.

We also use traditional microbiology, genetics, and molecular biology experiments. Our chemoproteomic efforts at PNNL are tightly coupled to our advanced measurement technologies and to our computational and data integration capabilities.

Highlights of our chemical proteomics research program include:

  • characterizing the functional, spatial, and temporal dynamics of microbes and microbial communities that impact organism and community properties such as resilience, resistance, and productivity
  • determining the function of drug/xenobiotic metabolizing enzymes in the mammalian liver and lung as a function of environmental exposure and developmental stage (age)
  • identifying the interplay between host and gut microbiome metabolic activities

To find descriptions of some of our ongoing projects, visit the pages of key researchers in this area: Aaron Wright and Weijun Qian.

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