Anthony A. Kossiakoff, University of Chicago, “Synthetic Antigen Binders: Novel applications for Structural and Cell Biology”

Feb 8 2011, 11:00 am
Distinguished Lecture Series Guest Speaker: 

Anthony A. Kossiakoff

Professor and Chair, Department of Biochemistry and Molecular Biophysics
University of Chicago

Date & Time: 
Tuesday, February 8, 2011, 11:00AM
Location: 
Klaus 1116E
Host: 
Jeffrey Skolnick
Abstract: 
Synthetic Antigen Binders (sABs) are a new class of antibody-based reagents engineered using novel phage display libraries. Using the power of phage display selection, it is possible generate sABs that: 1) target specific regions on the surface of a protein, 2) recognize specific conformational or oligomeric states, 3) induce conformational changes, and 4) capture and stabilize multi-protein complexes. Using these attributes, we can generate sABs that have their own functional properties and when introduced into cells can alter biological processes in defined ways. We have also employed them as crystallization chaperones to capture proteins in their most relevant states. As an example, the structure of the full-length KcsA potassium channel in both its closed and open states will be discussed. Further, we have also developed a cell delivery system that provides for introducing fully functional sABs into the cytoplasm for live cell imaging applications and to selectively alter cellular function.
Additional Info: 

Research Summary: 1) One of our research interests centers around studying at atomic resolution the structural and functional properties that define molecular recognition systems that activate and regulate biological properties. In particular, we study the energetics of hormone-induced receptor activation and regulation of growth hormone and its receptor using X-ray crystallography, site-directed mutagenesis, phage display mutagenesis and biophysical analysis. 2) Synthetic Antibodies- We use novel phage display libraries and screening procedures to produce a new class of synthetic affinity binders (sABs) based on Fab antibody scaffolds. These synthetic antibodies are much more versatile than traditional monoclonal antibodies and can be tuned to bind to multi-protein complexes and specific conformational states of their protein targets. These attributes make them the reagents of choice to study complex processes like cell signaling and cytokinesis. 3) Drug delivery- We have developed a unique drug delivery method that utilizes ligand-induced receptor-mediated endocytosis pathways. We call this method Receptor-Mediated Delivery (RMD) and have shown that we can deliver functionally active proteins and RNA/DNA cargoes into live cells for functional and imaging experiments. 4) Synthetic biology- We use a combination of peptide synthesis and phage display (biosynthetic phage display) to produce proteins with novel properties.

Faculty Website
Anthony Kossiakoff - Seminar Flier.jpg

Video: 
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