Research Seminar of Prof. Namjoon CHO from Nanyang Technologicval Universtiy(NTU)

Lecture Time: 09:00 on 5th April, 2016

Lecture Room: C501 of National Sicence Park

Lecture Title:Engineering Approaches to Combat Infectious Diseases

Prof. Nam-Joon Cho

^†School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue 639798, Singapore

^‡Centre for Biomimetic Sensor Science, Nanyang Technological University, 50 Nanyang Drive 637553, Singapore

^§School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive 637459, Singapore

Abstract

An amphipathic, α-helical (AH) peptide derived from the N-terminal region of the hepatitis C virus (HCV) NS5A protein represents a breakthrough, broad-spectrum antiviral drug candidate. It ruptures the lipid envelope of virus particles in a size-dependent manner. The size range of virus particles susceptible to treatment with AH peptide encompasses a wide range of deadly viral pathogens including dengue, HCV and HIV. Uniquely compared to other antiviral medicines in development or in the clinic, the virocidal activity of the AH peptide was originally discovered by surface science techniques probing model biological interfaces—namely lipid vesicles serving as surrogates for lipid-enveloped virus particles. Quartz crystal microbalance with dissipation (QCM-D) monitoring identified that addition of the AH peptide ruptures a layer of intact lipid vesicles to promote structural transformation to a planar lipid bilayer on gold and titanium oxide. Based on this in situ structural transformation, we have used simultaneous QCM-D monitoring and optical reflectometry to determine the antiviral mode of action of AH peptide, including a vesicle swelling process which occurs during the binding interaction. Using a newly developed total internal reflection fluorescence microscopy (TIRF)-based single vesicle assay, we have also investigated how AH peptide interacts with lipid membranes to induce membrane curvature-dependent pore formation and membrane destabilization. Importantly, the preference of AH peptide to selectively rupture virus particles of small size appears to be related to membrane strain-dependent pore formation. Compared to other known proteins and peptides, AH peptide is unique due to its combination of high potency and specificity for curved membranes. Collectively, these results lay the groundwork for the engineering of AH peptide therapeutics with optimized properties as well as for the broader application of surface science techniques to antiviral drug discovery and development.

Biography

Nam-Joon Cho is Nanyang Associate Professor in the School of Materials Science and Engineering at Nanyang Technological University in Singapore and Deputy Director of the Nanyang Institute of Technology in Health and Medicine. In addition, he is a Principal Investigator at the Singapore-MIT Alliance for Research and Technology. His group’s research focuses on engineering approaches to solve important biomedical problems and to translate these capabilities into practical applications for global health. Dr. Cho’s scientific work has been highlighted by international media organizations such as Reuters, CNBC, and Businessweek, and is leading to major breakthroughs for the treatment of deadly pathogens. He has identified novel classes of antiviral drugs to treat virus infections. Dr. Cho’s team is now actively working to examine the causes and consequences of infectious diseases in order to provide improved diagnostic and therapeutic interventions. Dr. Cho also leads a multi-institution tissue engineering collaboration involving NTU and the Stanford University School of Medicine, which focuses on developing an artificial liver platform for regenerative medicine applications. He is a graduate of Stanford University and the University of California, Berkeley.