Levitus garners prestigious NSF award

[Source: Joseph Caspermeyer, Biodesign Institute] - The Biodesign Institute’s Marcia Levitus has been named the recipient of a $568,000 National Science Foundation CAREER award, given to a very select group of young scientists deemed to be leaders in their respective fields.

With the prestigious award, Levitus will develop a finely detailed picture of how genes are controlled. “Our current understanding of how genes are turned on and off is very hazy,” Levitus says. “I believe that medicine will not be able to provide answers to how cellular processes lead to disease until we understand the most fundamental questions regarding how DNA is packed in our cells at the molecular level. But to get there, we still need to resolve many open puzzles regarding how DNA bends and wraps around proteins. We are reaching an exciting quantitative era in biology where it is possible to address these questions with tools traditionally used in the physical sciences.”

Typically, an organism’s complete genetic information, or genome, contains anywhere from 10 million to 100 billion DNA letters spaced out along chromosomes. If all of the DNA were stretched out from end to end, it would be up to six feet long. Somehow, the threads of DNA must be finely spooled and stuffed into the cell’s nucleus, a space about 10 times smaller than the width of a human hair. “Understanding how DNA is packed inside the nucleus of the cell is necessary to decipher fundamental processes in cell physiology,” Levitus says. “This knowledge will improve our very limited understanding of how genes work, which will aid the understanding of biological processes including aging and cancer.”

The core DNA packaging unit is called a nucleosome, which acts like a protective armor for the DNA code. It can take just a single nick, or a misplaced or lost letter in the DNA code, to cause the development of diseases such as cancer. But nucleosomes also must fill the role of a genetic conductor, helping to orchestrate all of the DNA information in a cell to be copied, read, and turned on and off at precisely the right tempo. Levitus, a researcher in the institute’s Center for Single Molecule Biophysics and assistant professor of chemistry and biochemistry and physics, is attempting to create a quantitative model of the first triggering events in this cascade. Her research focuses on the smallest unit of DNA packaging – a single nucleosome – where 147 letters of the DNA code are wrapped twice around a core octet of proteins.

The energetics of this process requires a cellular feat of strength. Levitus explains that DNA is a very stiff material, with a physical strength similar to a thin cylinder made of Plexiglas. “The physics of DNA bending around the nucleosome is not that well understood, but I am trying to understand the physics of how the DNA sequence influences the ability of DNA to bend around the nucleosome,” she says. To help reach her research milestones, Levitus is collaborating with Northwestern University researcher Jonathan Widom, whose recent groundbreaking work has shown that nucleosomes seem to prefer to assemble at preferred positions within the DNA sequence – the first important steps to uncovering a nucleosome positioning code that may be hidden within every genome.

Levitus’ research grant also is important for its social commitment. As a native of Buenos Aires, Argentina, she is particularly interested in increasing participation of women and Hispanic students into the sciences. “There are not too many women in the physical sciences, and as the scientific field becomes more quantitative, the number of women goes down,” Levitus says. “It’s a very sad fact, and I think it’s terrible that more women don’t go into this field. I also realize from talking with Hispanic undergraduates that they often feel like they don’t belong in science.” To overcome these barriers, Levitus works one-on-one in the classroom as a role model and mentor to encourage more minority women to participate in the physical sciences.

In addition, many students with interests in biochemistry and the life sciences can struggle with the math and basic numerical skills that have become increasingly indispensable for today’s interdisciplinary and large team approach to solving science problems. “My research exemplifies the increasing demand for quantitative reasoning in today’s biochemical and biological research, and shows the importance of applying concepts from the physical sciences to address basic questions involving biological systems,” Levitus says. “My background allows me to teach biochemistry students to think in quantitative terms, and make them appreciate the importance of learning math and physics. I want them to realize that otherwise they will not be able to face the challenges found in some of the most exciting problems of today’s biochemical research.”