University of Minnesota
Medical School
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Chemical Biology and Proteomics Research                 

Posting expires on 12/31/2019

Research Site:
University of MInnesota - Twin Cities

Type of Research:
Basic Science

Department:
Biochemistry, Molecular Biology and Biophysics

This opportunity does not have a stipend.

Description:
Our research program is broadly directed at assay development for post-translational modifications (PTMs), with a focus on protein phosphorylation by tyrosine kinases. Protein tyrosine kinases play key roles in disease and are particularly important in cancer: mutations in several protein tyrosine kinase genes have been identified as drivers of many tumor types and drugs targeted at inhibiting these enzymes represent ~20% ($9 billion) of the current oncology market. We use a decoy substrate biosensor approach in which an artificial, optimized substrate peptide is designed to report the activity of a specific enzyme in living cells. Delivery is achieved using cell-penetrating peptides, and enzymatic modification is measured using a range of readout strategiessome that require extraction of the cell contents and some that leave the cell intact. Targeting the function of the enzyme in its intracellular environment preserves protein-protein interactions, localization, and scaffolding-dependent activation, and decoy substrates provide a snapshot of enzymatic activity that circumvents the need for pre-knowledge of every endogenous substrate site. We also develop multiplex-compatible readouts, so we can use a suite of biosensors for different enzymes in order to profile pathways. We have established our approach and laid the groundwork of a substrate development workflow to expand our repertoire of biosensors for kinases and other enzymes. Long term, our lab will maintain a pipeline of biosensor and read-out technology development while also taking an active role in studying signaling biology with our tools.

If interested, please email a CV and cover letter to Dr. Laurie Parker (llparker@umn.edu). Please describe any previous research experience you have had, and explain why you are interested in our research. 

More information

Posted on 01/05/2015