Aleksei Aksimentiev
The opportunity is great but so are the expectations. A lot is riding on the outcome of DNA sequencing research and technology development, including researchers hope, results that will some day allow the early diagnosis and treatment of diseases that have resisted medical efforts until now.
Last year the National Human Genome Research Institute (NHGRI) announced a $32 million grant program aimed at accelerating research for a breakthrough gene sequencing technology that is accessible, fast, and inexpensive. The name of the grant program — Revolutionary Genome Sequencing Technologies — portends both its purpose and its desired effect on medical research. The hope is to dramatically change everything from treatment to cost to the gathering of scientific knowledge through low-cost, efficient DNA sequencing. By revealing the information found in DNA (deoxyribonucleic acid), a chemical compound containing the genetic instructions all organisms need for development and direction of their activities, the genetic basis for pathologies such as cancer or heart disease could be found.
A team of researchers at the Beckman Institute for Advanced Science and Technology was one of the groups awarded grant money, receiving $2.1 million for sequencing a DNA molecule using a synthetic nanopore. The group includes top scientists from the fields of computational electronics (Jean-Pierre Leburton and Gregory Timp), theoretical biophysics (Klaus Schulten) and chemistry (Steven Sligar).
There is one more member of the team who is not yet as well known, but who has already contributed one of the group's first big breakthroughs. Using software from Schulten's Theoretical and Computational Biophysics group, researcher Aleksei Aksimentiev was able to do the first-ever simulation of DNA translocation through a synthetic nanopore.
It was an important first step in the team's goal of creating what has been referred to as a low-cost, reliable “gene chip” for sequencing DNA. The technology would use a type of silicon integrated circuit that incorporates a nanopore mechanism through which DNA molecules are forced. The narrow nanoscale opening changes the structure of single strand DNA, causing its base to tilt and the molecules to oscillate back and forth, thereby producing a unique electrical signal. These signals can then be read for the information contained in the individual DNA.
Each member of the team has a specific role in bringing a gene chip to reality. But for Aksimentiev, who knew little of biophysics three years ago, membership on the team is more than a role. It is the realization of an unexpected opportunity.
Aksimentiev grew up in the Ukraine with parents who are scientists — his mother is a chemistry professor and his father a physicist. He earned a cum laude Ph.D. in chemistry from the Institute of Physical Chemistry in Warsaw, Poland.
DNA research wasn't part of Aksimentiev's curriculum vitae when he came to Illinois in 2001. But he saw an opportunity with Schulten's group — known worldwide for molecular dynamics simulations — and was not afraid to follow his instincts. He wrote to Schulten while working for a private company in Japan because, he said, “I was in particle physics and polymer theory and I just wanted to do theoretical biophysics. And the theoretical biophysics group of Klaus' is probably the best.”
After joining TCBG, Aksimentiev worked on ATP synthase, a large multi-protein complex. It was during that time that he heard about the gene chip project.
“To me it looked like a fantastic thing,” said Aksimentiev, an Assistant Professor of Physics at the University of Illinois. “It was a project that didn't have enough people computation-wise. It looked very, very attractive to me.”
Aksimentiev joined the project enthusiastically.
“I thought it was a fantastic idea of bringing silicon and biomolecules into one thing, and nanopores is just one example of that,” he said. “Plus it's very important, because if it succeeds it will be something that is very useful.”
How useful may not be known for 10 or 20 years, but the potential applications of gene research are revolutionary. The NHGRI is the government agency behind the Human Genome Project, which sequenced and mapped the human genome (the aggregate of the genes of Homo sapiens) in 2003, allowing scientists to read the complete genetic blueprint for a human being.