Hexameric AAA+ DNA Translocation Nanomotor of Cell and Virus for Single Molecule Sensing, Single Pore DNA Sequencing, Bioreactors and Specific siRNA Delivery

Date:
-
Location:
CP-137
Speaker(s) / Presenter(s):
Dr. Peixuan Guo, UK Pharmaceutical Sciences

Dr. Peixuan Guo of UK's Pharmaceutical Sciences will be presenting a seminar entitled, Hexameric AAA+ DNA Translocation Nanomotor of Cell and Virus for Single Molecule Sensing, Single Pore DNA Sequencing, Bioreactors and Specific siRNA Delivery.

Abstract: AAA+ family is a class of motors involved in chromosome segregation, nucleic acid replication, DNA repair, genome recombination, viral DNA packaging, and translocation of cellular components. Many of these motors display hexameric arrangements to facilitate DNA motion triggered by ATP.  For 35 years it has been popularly believed that viral DNA packaging motor runs through a five-fold/six fold mismatch rotation mechanism.  In 1998, a hexameric RNA ring was discovered in the bacteriophage phi29 DNA packaging motor (Fig. 1) and I proposed that the mechanism of the viral DNA packaging motor is similar to that used by the hexameric DNA tracking AAA+ family  (Guo et al., 1998, 2: 149-155).  This notion has caused a fervent debate since then concerning whether the RNA and the motor ATPase is a hexamer or a pentamer.  Our recent X-ray diffraction of RNA crystals, AFM imaging, and single molecule studies have confirmed that the motor is composed a three-coaxial rings with a hexameric RNA ring,  a hexameric ATPase, and a dodecameric motor channel that allows one-way traffic for the movement of dsDNA.  A novel and unexpected motor mechanism has also been discovered that is completely different from the five-fold/six-fold mismatch mechanism that has been popular for several decades. We also found that several cellular DNA packaging motors use almost the same mechanism as we discovered in the motor of phi29.  My presentation will focus on how to apply the unexpected mechanism of the motor and its novel structural components for RNA nanotechnology, single molecule sensing, single pore DNA sequencing, bioreactors, real-time intracellular RNA monitoring,  specific drug loading, and delivery of siRNA, miRNA, ribozyme, aptamer and drugs to cancer and viral infected cells. 

Bio: Dr. Peixuan Guo is the William Farish Endowed Chair in Nanobiotechnology and the director of the Nanobiotechnology Center at the University of Kentucky. He also serves as the director of the NCI Cancer Nanotechnology Platform Partnership Program: RNA Nanotechnology for Cancer Therapy.

He received his Ph.D. in Microbiology/Genetics with training in biophysics from the University of Minnesota in 1987; was a post-doc at NIH before joining Purdue University as an assistant professor in 1990, was tenured in 1993, became a full Professor in 1997, and was honored as a Purdue Faculty Scholar in 1998. He was recruited to the University of Cincinnati as Dane & Mary Louise Miller Endowed Chair of Biomedical Engineering in 2007, and served as the Director of the NIH Nanomedicine Development Center from 2006-2011. He moved to University of Kentucky as William Farish Endowed chair in nanobiotechnology in 2012.
 
He constructed the phi29 DNA packaging motor (PNAS, 1986), discovered the phi29 motor pRNA (Science, 1987), assembled infectious dsDNA viruses (J Virology, 1995), discovered the pRNA hexamer (Mol Cell, 1998), and pioneered RNA nanotechnology (Mol Cell, 1998, JNN, 2003; Nano Lett., 2004,2005; Nature Nanotechnology, 2010). His lab built a dual imaging system to detect single-fluorophores (EMBO J, 2007; RNA, 2007), and incorporated the phi29 motor channel into a lipid membrane (Nature Nanotechnology, 2009) for single molecule sensing with potentials for high throughput dsDNA sequencing.
 
He received the Pfizer Distinguished Faculty Award in 1995; the Purdue Faculty Scholar award in 1998; the Purdue Seed Award in 2004, 2005, and 2007; the Lions Club Cancer Research Award in 2006; and the COV Distinguished Alumni of the University of Minnesota in 2009, Distinguished Research Faculty Award in 2010 and 2011. He is an editor or board member of five nanotech journals. His work has been reported hundreds of times over the radio and TV stations such as ABC and NBC, and featured in the newsletters or websites of NIH, NSF, MSNBC, NCI, and ScienceNow, to name a few. He was a member of two prominent national nanotech initiatives sponsored by NIST, NIH, NSF and the National Council of Nanotechnology; and a member of the NIH NDC Steering Committee from 2006-2010. 
 

Faculty Host: Dr. Chris Richards