2009 High Performance Computing Grant Winner Profiles

Pictured (L to R) holding the check are grant winners Jesse Ziebarth and Yongmei Wang from the University of Memphis. Pictured L to R, back row, are ORAU Board Chair Win Phillips, ORAU Council Chair Sandra Degen, Interim ORAU President Homer Fisher and Deputy Associate ORNL Lab Director for Computing and Computational Sciences Jeff Nichols.

Dr. Yongmei Wang

Associate Professor, University of Memphis, Department of Chemistry

ORAU Member Councilor
Dr. Andrew Meyers

Research Focus
Delivering therapeutic genes and the DNA they contain into cells.
This research relates to the technology known as gene therapy, which involves inserting genes into a person’s cells and tissues to treat a disease. A critical step in gene therapy is the successful delivery of a therapeutic gene into the cells. This is usually achieved by using delivery agents—also known as delivery vectors—that would condense the DNA and thus provide protection against degradation caused by enzymes and enable efficient delivery.

Earlier clinical trials of gene therapy used viral particles as delivery vectors, but these led to severe immune responses in several patients. Now scientists working in gene therapy are looking for non-viral-based delivery vectors. Positively charged polymers are promising non-viral-based delivery agents. In this project, Dr. Wang and co-researchers are trying to simulate how non-viral-based delivery agents like polymers may condense the long DNA helix.

Although many earlier studies examined DNA condensation, they mostly used coarse-grained modeling techniques. In coarse-grained modeling, DNA structures were unfortunately misrepresented and chemical details of delivery agents were ignored. Atomic-scaled simulations are needed to gain insight into how non-viral-based gene delivery vectors interact with the DNA helix. Such simulations are extremely computer time and resource consuming.

“Our preliminary studies, performed at the high-performance computing facility at our home institution, were limited to simulations with 12-base pairs of DNA,” Dr. Wang said.

What does it mean to you to win this grant?
“Winning this grant means a lot to me. This research project is a new one started in my group from scratch in fall 2006. My graduate student, Jesse Ziebarth, has played an important role in defining and shaping the research for this project. While my group currently has several other funded projects by the National Science Foundation; the Petroleum Research Fund, administered by the American Chemical Society; and the National Institutes of Health, this project is at the heart of our interest.”

“The computational and financial supports provided by this grant now allow us to pursue this project with sufficient resources and to push the research activities to a level that would otherwise be impossible to achieve.”

What are you most looking forward to in working with ORNL’s computing resources and staff?
“My students and I are looking forward to using the computing resources at ORNL and interacting with staff there. We are thankful to ORAU/ORNL for supporting our research effort and also thankful to our administrators at the University of Memphis who had wisely invested in the local high-performance computing facility since 2006. Without the on-campus high-performance computing facility, we would not be able to obtain the preliminary results for this project, nor would we be in a position to win this award.”

How will others (your students, the research community, your university, etc.) benefit from what you plan to accomplish through your research under this grant?
“With access to ORNL computing resources, we will now be able to examine DNA condensation at atomic scale for much larger systems under a variety of conditions. These simulations will enable us to provide useful information to experimentalists developing non-viral-based gene delivery vectors.”