Nano@Tech: The Design of Nanoscale Therapeutics and Nanostructured Materials

Prof. Ravi Kane - Garry Betty/V Foundation Chair and GRA Eminent Scholar in Cancer Nanotechnology, School of Chemical and Biomolecular Engineering, Georgia Tech

Abstract: 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 can neutralize anthrax toxin 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. The ability to control independently the valency and the spacing between ligands is particularly valuable for these design efforts. To that end, we recently designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin 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. Studies relating the composition and structure of polyvalent inhibitors to their activity have also shed light on fundamental aspects of polyvalent recognition, including the role of “pattern matching”. We will also discuss other applications of polyvalent molecules ranging from the inhibition of pathogens (e.g., the influenza virus) to controlling the nanoscale organization of cellular receptors to regulate 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 have also investigated the structure and function of these and other enzymes when immobilized onto nanomaterials such as carbon nanotubes. Our studies indicate that the nanoscale environment can significantly influence the activity and stability of these proteins. We have used the highly stable and active nanomaterial- protein conjugates to form nanocomposite films that are effective against antibiotic- resistant bacteria including methicillin-resistant S. aureus (MRSA).

Bio: Prof. Kane received a B.S. in Chemical Engineering with distinction from Stanford University in 1993. While at Stanford University, he received the Terman award for outstanding achievement in engineering, the American Institute of Chemists outstanding senior award, and was elected to the Tau Beta Pi and Phi Beta Kappa honor societies. Prof. Kane went to graduate school at MIT, where he received an M.S. in Chemical Engineering Practice and a Ph.D. in Chemical Engineering working with Bob Cohen and Bob Silbey. While at MIT, he was an NSF graduate fellow and was elected to the Sigma Xi honor society. After postdoctoral research with George Whitesides in the Department of Chemistry and Chemical Biology at Harvard University, Dr. Kane joined Rensselaer Polytechnic Institute as an assistant professor in 2001. He was promoted to associate professor in 2006 and to full professor in 2007 prior to his promotion to P.K. Lashmet Professor in 2008. In 2004, Prof. Kane was named by MIT’s Technology Review as one of the TR100 – the top 100 young innovators in the world. Prof. Kane received the AIChE Nanoscale Science and Engineering Forum Young Investigator Award in 2008, the ACS BIOT Division Young Investigator Award in 2009, and the RPI Trustees Outstanding Teacher Award in 2011. Prof. Kane was elected to the AIMBE college of fellows in 2013 and received the SBE Biotechnology Progress Award for Excellence in Biological Engineering Publication in 2014. Prof. Kane joined the faculty at Georgia Tech in 2015.