Bioengineering Seminar Schedule

Summer, 2008 (For prior semesters, click here: Fall 1999, Spring 2000 , Fall 2000, Spring 2001, Fall 2001, Spring 2002, Fall 2002 Spring 2003, Fall 2003 , Spring 2004 Summer 2004, Fall 2004, Spring 2005, Fall 2005, Spring 2006, Fall 2006, Spring 2007, Fall 2007, Spring 2008

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Thursday,June 12, 2008, 11:00 a.m. - 12:00 p.m., Room 210 Hallowell, CG623 Hershey
Jordan Green
Massachusetts Institute of Technology
"Enhanced Polymeric Nanoparticles for Gene Delivery"

Abstract

The potential of gene therapy to treat disease and improve human health is tremendous. The failure of viral gene therapy clinical trials due to toxicity, immunogenicity, and carcinogenicity has been tragic and strongly motivates a non-viral approach. Polymeric nanoparticles composed of poly(beta-amino esters) (PBAEs) and DNA can be formulated to be stable in the presence of serum proteins and have high gene delivery without toxicity to human primary cells. In comparison to the previous "gold standard" for polymeric transfection, 25 kDa polyethylenimine, the PBAE nanoparticles presented here have 100x higher efficacy while simultaneously having 100x lower toxicity. Small structural changes to the polymer were found to have dramatic effects on multiple steps of gene delivery including the DNA binding affinity, nanoparticle size, intracellular DNA uptake, final protein expression, and in vivo efficacy. As the enhanced polymeric gene delivery nanoparticles described here have virus-like efficacy and many attractive properties over a virus including high safety, high nucleic acid cargo capacity, ease in manufacture, a coating method for targeted delivery, and flexibility for future design improvements, these nanoparticles may be promising for many therapeutic applications including cancer therapy, genetic vaccines, and regenerative medicine.

Monday, June 23, 2008, 12:00 - 1:00 p.m., Room 210 Hallowell, CG623 Hershey
Ramachandra Gullapalli - CANCELLED
Final Defense
"Integrated Experimental, Computational and Theoretical methods to study the Molecular Dynamics of Stressed Membranes"

Abstract

Cells transduce forces into biochemical signals through a process termed mechanotransduction. This process involves transmembrane proteins, the activity of which is modulated by the lipid solvent surrounding them. The goal of this work was to develop the experimental, computational and theoretical infrastructure to study the direct interrelationship between force and lipid dynamics. First, fluorescence correlation spectroscopy (FCS) and fluorescence lifetime methods based on time-correlated single photon counting (TCSPC) instrumentation were developed in order to capture the force-induced change in lipid dynamics on spatial and temporal scales relevant to mechanotransduction. In tandem, the infrastructure was developed and tested for micropipette aspiration of giant unilamellar vesicles (GUV's) stained with lipoid dyes such as DiI-C18(3). These systems will be used for direct interrogation of the relationship between membrane tension and molecular dynamics. Second, we developed atomistic computational molecular dynamics (MD) simulations of a lipoid fluorescence dye, DiI-C18(3), in a DPPC bilayer. From these simulations, we clarify, for the first time, the location of DiI-C18(3) within a bilayer and compare the computational data to experimentally available data. Third, a generalized analytical model was developed that shows an exponential relationship between membrane lateral stretch and lipid diffusion; a relationship that can be tested directly on stressed GUVs using single molecule fluorescence methods. This infrastructure provides tools to determine, from atomic to continuum scale and from nanosecond to minute time scales, the role of plasma membrane lipids in mechanotransduction.

For additional information, contact Ms. Doretta Garvey, Dept of Bioengineering, Tel: 814.865.1407 or E-Mail: bioe@engr.psu.edu