University of Toronto
Talk Session: SESSION 6: PEPTIDE LIBRARIES, ARRAYS AND PROTEOMICS
Date: Monday, June 13, 2022
Talk Time: 03:00 pm - 03:25 pm
Talk Title: Rational Design & Continuous Evolution of Franken-Proteins: Potential Drugs & Synthetic Biology Tools
The multidisciplinary Shin lab focuses on exploiting the building blocks that nature uses, including proteins and nucleic acids, toward solving problems in human health and our environment and ecosystem. We design small proteins that bind to specific DNA targets toward regulation of gene expression, particularly those involved in cancer and disease. Protein structure and function is analyzed by various spectrosopic methods including fluorescence, FRET, anisotropy, circular dichroism and x-ray crystallography, as well as biological assays (yeast and bacterial one-hybrid) and testing in cancer cell lines and mouse models.
Nanomaterials are part of our daily lives, in our cell phones, TVs, paints and coatings, and more, so we are trying to understand how nanomaterials can exert pressure on organisms in the environment to evolve. Using a multidisciplinary approach involving quantitative genetics, nano-engineering, and molecular biology, we observed that chronic exposure to nanomaterials can cause organisms to mutate their genomes in order to survive.
Our transdisciplinary approach borrows from biophysics, molecular biology, and chemistry to explore how nature uses the protein scaffold to target specific DNA sequences. We combine rational design and continuous evolution to develop our DNA-binding minimalist proteins as possiblel drugs against cancer and asthma, and new Franken-proteins that can orthogonally target gene circuits in synthetic biology applications.
We use our protein design know-how and phage-assisted continuous evolution, PACE, to develop small proteins that target the Myc/Max/E-box network involved in >50% of all cancers. We are now expanding into designing new protein motifs incorporating intrinsically disordered regions that target large DNA sites with utility in synthetic biology.