Research Feature . . .
CODE BREAKER: Engineer Receives Early Career Award from DOE
By Pam Frost Gorder
It drives the most basic cellular processes in all life on Earth, but how it works is a mystery. Protein folding -- why long chains of protein molecules twist and loop to form useful shapes -- seems to depend on some unknown chemical code.
With a new award from the Department of Energy (DOE), an Ohio State engineer is out to break that code.
Srinivasan Parthasarathy has received DOE’s Early Career Principal Investigator (ECPI) award, which helps exceptionally talented computer scientists develop research programs early in their careers. The assistant professor of computer science and engineering will use his $310,000 three-year award to develop tools to associate protein structural motifs with function, and help determine why proteins fold the way they do.
With joint appointments in biomedical informatics and biomedical engineering, he is one of a growing number of scientists and engineers who are using today’s powerful computers to confront grand challenges in the life sciences.
William A. "Bud" Baeslack III, dean of the College of Engineering at Ohio State, pointed out that the new award comes just one year after Parthasarathy won a similar honor.
"Dr. Parthasarthy's selection as a DOE ECPI Award winner, coupled with his prestigious NSF CAREER Award in 2003, is a testament to the excellence and impact of his innovative research in the university's priority area of bioinformatics," Baeslack said.
Protein folding has baffled scientists since the early 1960s, when they discovered that all proteins are essentially re-arrangements of the same 20 amino acids, strung together in chains that are sometimes hundreds of amino acids long.
Scientists can spell out a chain in letters (for example, “A” for the amino acid alanine, “C” for cysteine), but they can’t tell how a chain will function until they see how that alphabet connects in three dimensions. Some unknown factor causes a protein chain to twist like an overwound rubber band into just the right shape to grab onto some other molecule and make things happen in a living cell.
The loops and whorls on a protein’s surface form a kind of alien landscape, and Parthasarathy will be looking for patterns in the topology -- clues as to why amino acids connect the way they do.
What excites him most about his new project is that he will be developing tools that have “clear medical and scientific benefits.”
If scientists could better understand what makes proteins fold a certain way, they could eventually make custom proteins that fold on demand. That advance could lead to new therapies for diseases such as Alzheimer’s, Parkinson’s, and the most common form of diabetes -- all of which arise when protein folding goes wrong in the body. Chemical industries could make custom enzymes and catalysts; proteins could even be used as tiny machines to build devices for nanotechnology.
Parthasarthy’s task, then, is to find ways for scientists to model biological data efficiently and get the information they need to predict how a particular protein structure will function. He will also develop tools for predicting the best conditions for crystallizing proteins. The resulting structures, extracted via X-ray crystallography, can in turn be analyzed.
DOE awarded nearly $2 million in ECPI funding in 2004, to institutions including the Massachusetts Institute of Technology, Boston University, and University of Chicago. Begun in 2002, the ECPI program helps researchers establish careers in applied mathematics, computer science, and high-performance networking.