“The Design of Nanoscale Therapeutics and Nanostructured Materials”
This talk will describe our efforts to interface bioactive molecules with nanomaterials and nanoscale scaffolds for designing potent therapeutics and functional nanocomposites.
The design of polyvalent molecules presenting multiple copies of a specific ligand represents a promising strategy to inhibit pathogens and bacterial toxins. We will first describe the design of polyvalent inhibitors that are orders of magnitude more active than the corresponding monovalent molecules and effective in vivo. We recently described a thermodynamic analysis to help clarify the theoretical basis for the large enhancements in avidity due to polyvalency. We have used this understanding to guide the structure-based design of potent synthetic polyvalent ligands. We will describe the design of monodisperse polypeptide-based polyvalent inhibitors in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers. By tuning the valency and linker length, we designed polyvalent inhibitors that were over four orders of magnitude more potent than the corresponding monovalent ligands. We will also discuss other applications of polyvalency ranging from the inhibition of pathogens (e.g., the influenza virus) to the design of vaccines and the regulation of signaling and stem cell fate.
In addition to the inhibition of bacterial toxins, we are also investigating approaches to target pathogenic bacteria. In particular, the emergence of antimicrobial resistance has been a growing concern. We have been exploring an enzyme-based approach to combat pathogenic bacteria. We will describe an approach that we have developed to identify novel bacteriolytic enzymes targeting a variety of bacterial pathogens. We will also discuss the design of highly stable and active nanocomposite films that are effective against antibiotic-resistant bacteria.
Ravi Kane is the Garry Betty/ V Foundation Chair and GRA Eminent Scholar in Cancer Nanotechnology. He received a B.S. in Chemical Engineering from Stanford University in 1993. Also, he received an M.S. in Chemical Engineering Practice and a Ph.D. in Chemical Engineering from MIT, working with Bob Cohen and Bob Silbey. After postdoctoral research with George Whitesides in the Department of Chemistry and Chemical Biology at Harvard University, he joined Rensselaer Polytechnic Institute (RPI) as an assistant professor in 2001. He was promoted to associate professor in 2006, to full professor in 2007, and to the P.K. Lashmet Professor in 2008. He served as the head of RPI’s Howard P. Isermann Department of Chemical and Biological Engineering before moving to Georgia Tech in 2015. Prof. Kane has graduated 27 Ph.D students and contributed to over 130 scientific publications.