Biophysics, Physical Science
The Quantitative Biology Research Community at Brandeis (QBReC)
In 2000, Jane Kondev was settling into a professor position at Brandeis University. He'd been awarded research grants and assembled a talented team, and his work in condensed matter theory was energizing and exciting. But so too was a conversation he had over coffee one afternoon, when he and a colleague began to consider something new to both of them: biology. That conversation launched what Kondev calls the greatest intellectual adventure he has ever undertaken – one that redirected every aspect of his research program and his teaching.
Kondev earned a PhD in physics at Cornell University, where he studied novel states of magnets and the fractal geometry of level lines on random surfaces. During postdoctoral research at Brown and Princeton, he came up with a strategy to solve a class of problems in random geometry by establishing a connection between fluctuating loops and field theory. Developing mathematical models to explain how the world worked captured his interest in a way that biology had not.
That changed when Kondev and fellow physicist and friend Rob Phillips started to discuss what they were hearing about big questions that biologists were grappling with. “We didn't know any biology, but there seemed to be a lot of interesting problems that would benefit from theory as practiced by physicists,” he recalls. Kondev and Phillips sensed an opportunity, but they had a lot of catching up to do. So to educate themselves about biology, they decided to write a book.
The project quickly became a focal point of Kondev's activities. For eight years, he and Phillips talked daily, working their way through a cell biology textbook and discussing how key concepts might be expressed mathematically. Soon the pair was joined by Stanford cell biologist Julie Theriot (now an HHMI investigator) and Berkeley’s Hernan Garcia, also a physicist. Together, they worked to “turn the cartoons of cell biology into mathematics.”
Their book, Physical Biology of the Cell, was first published in 2008, and has become a standard reference for undergraduate biophysics and biochemistry courses. But the thousand-page book was not the only outcome of the research that went into it. Along the way, Kondev and his coauthors uncovered several concepts that he has explored in his own theoretical work, and his predictions and conclusions have influenced the research directions of well-established biology labs.
In 2003, Kondev and his fellow physical biologists provided a mathematical description for how DNA is packed into a bacteria-infecting virus, using data from experiments measuring the force exerted in individual viruses during packing. The theoretical work suggested new experiments to address whether viruses use the internal pressure that builds during DNA packing to inject their genetic material into host cells. His group has also developed a theory to predict how much protein a gene will produce in the presence of any given combination of activators and repressors, and how the cell-to-cell variability of gene expression is regulated. With geneticist Jim Haber he has determined how chromosome folding in the cell nucleus directs repair of DNA breaks. Working together with cell biologist Bruce Goode, he determined how yeast cells control the size of actin cables, the bundles of filaments that traverse a cell and are required for transport of cellular cargo. Now, in a collaboration with synthetic biologist Mo Khalil, Kondev's group is making yeast cells that act as “logic gates,” producing proteins only when two specific chemicals in the cells environment are each present at high levels. The goal, he says, is to figure out the design principles of molecular circuits that control gene expression in cells.
Teaching has always been a priority for Kondev; among his proudest accomplishments are two Excellence in Teaching awards he received from Princeton University students prior to coming to Brandeis. He wants his students to appreciate science as a dynamic, interdisciplinary endeavor, and he teaches them that it's a dialogue with nature, not a set of laws: “Science constantly asks us to reconsider our notions of how nature works,” he says. Science won't provide definitive answers, he explains; instead, it provides the tools to ask questions and begin to answer them.
For ten years, Kondev has taught a course called “Nature's Nanotechnology,” which introduces first-year undergraduates to current--and sometimes controversial--research at the interface of physics and biology. The idea, he says, is to demonstrate how the math and physics that students already know can shed light on biological phenomena.
Students who decide they want to apply the tools of math and physics to modern biology problems can prepare for a research career through the university's Biological Physics major, which Kondev co-developed in 2006. He also founded and co-directs a graduate program in Quantitative Biology, which aims to educate the next generation of scientists working at the interface of the physical and life sciences. The program was started in 2005 with an Interfaces grant from HHMI.
Now Kondev is planning to create new opportunities for undergraduates to immerse themselves in quantitative biology research at Brandeis. As an HHMI professor, he will launch a program that will introduce students to science in an integrated fashion, beginning with a course for first-year students that combines physics, chemistry, biology, and mathematics to describe living systems. In the laboratory portion of the new first year course, students will be placed in Brandeis research labs in teams of two, where they will spend six weeks collaboratively investigating specific biological problems. The program will create a community of student researchers working in different science disciplines, who will support and learn from one another throughout their time at Brandeis.