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Systems Biology
Systems Biology, the New Physiology, Marks First Year at HMS
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Systems Biology, the New Physiology, Marks First Year at the Medical School
One of the most frustrating things that can happen when you try to repair something as complex as a fine Swiss watch is that you get the watch to work, but have pieces left over. Biology, which is far more complex, can be similarly enigmatic. You can knock out a gene, for example, and see no apparent change in phenotype. Does this mean that the "spare" gene, probably retained through millions of years of evolution, has no function? Or does it imply that science has not fully appreciated how the gene fits into a much bigger picture?
Clockwise from top left, Lew Cantley, Pam Silver, Tim Mitchison, and Marc Kirschner are part of the core of the year-old Systems Biology Department. (Photo by Leah Gourley)
The second answer is more likely. A craftsman from Geneva may tell you that the tiny parts you are now storing in a plastic bag would save your timepiece from losing a minute a week. But it is systems biology, a discipline that aims to understand how all the minute biological parts fit together to make a dynamic whole, that can reveal the cellular balances that are tipped by removing just one component.
Next Thursday, Sept. 23, marks the anniversary of the establishment of HMS's Department of Systems Biology, the first completely new basic science department in more than 20 years. Under the direction of Marc Kirschner, who chaired the Department of Cell Biology for 14 years and who is now the Carl W. Walter professor of systems biology, the new department aims to tackle some of the most challenging questions in modern biology. It focuses on how all the different molecules in a cell, particularly human cells, can work together as a cohesive unit, one that can on one hand detoxify like a hepatocyte, and on the other, keep time like a heart muscle. Ultimately, systems biology aims to accurately model the physiology of complex organisms.
Physiology as Future
In fact, the new department was conceived with physiology in mind. Almost two years ago, shortly after Kirschner had addressed the heads of the clinical departments on the future of basic science, he and HMS dean Joseph Martin agreed that the study of physiology needed revitalizing. "Though it sounds like the past, physiology is actually the future," said Kirschner. While he emphasized that much classical physiology was supported by some extraordinary science, it was not based on a molecular understanding. "We now have the opportunity to vastly increase our level of understanding," he said.
| "Though it sounds like the past, physiology is actually the future." |
To build on the founding faculty--Kirschner, Tim Mitchison, who is now the Hasib Sabbagh professor of systems biology, and Lew Cantley, HMS professor of medicine at Beth Israel Deaconess--the department has undertaken a recruitment drive. Eric Lander, who has a joint appointment at the Broad Institute, and Pamela Silver, now an HMS professor of systems biology at Dana-Farber, were recruited from the Department of Biological Chemistry and Molecular Pharmacology soon after the new department was established.
Education will be a major focus for Systems Biology. Courses available next year will include an undergraduate offering through the Faculty of Arts and Sciences at the Cambridge campus and a graduate course taught by Mitchison and Silver. Kirschner is particularly motivated by the educational mission. "There is tremendous emphasis these days on the amount of material that students need to get through, but they also need to know that there are many unanswered questions," he said. Next fall the department hopes to launch a graduate program that will lead to a PhD degree in systems biology. Working with colleagues at FAS, particularly from the Division of Engineering and Applied Sciences, the department has submitted a program proposal to the Graduate School of Arts and Sciences that is currently under review.
Critical Mass
How does a school ensure that a brand new department, based on a scientific rationale that very few have even pursued, will succeed? The key for systems biology, suggests executive director Rebecca Ward, is to generate a critical mass of researchers who think about biology from theoretical, computational, and engineering perspectives and who will together drive the science forward. So the department has deliberately searched for recruits outside of the normal "comfort zone," said Ward, looking for scientists who have started their careers in disciplines such as mathematics, engineering, physics, and computer science.The department's goal is to grow to include 20 to 25 tenure track positions at all levels. As of now, the total faculty number has been brought to nine with the addition of four new faces: Walter Fontana, a theoretician and mathematical chemist with a deep interest in design principles underlying biology; Vamsi Mootha, trained as a mathematician, who specializes in genetic and proteomic approaches to human disease; Galit Lahav, a biologist with postdoctoral training in theoretical approaches, who is interested in circuitry in single cells and who recently discovered that the tumor suppressor p53 is expressed in rhythmic pulses after DNA damage; and Jeremy Gunawardena, a mathematician with a long track record in computer science who is now developing a new computer language that can be used for molecular modeling.
"Over the past 20 years, the vast complexity of biological systems has become apparent from sequencing of complete genomes and from experiments that monitor cellular or organismal responses to mutations or other perturbations. It has become clear that the complexity of these systems has begun to exceed the intuitive capacity of the human brain. It is exciting to be at the beginning of an effort to assemble a group of scientists with diverse expertise but with a common interest in generating the experimental and computational tools required to approach these problems," said Cantley.
Systems biology is a logical follow-up to the years of reductionist biology that have culminated in the sequencing of the human genome. Just as having all the springs, jewels, wheels, and cogs spread out on the bench is of little help in figuring out exactly how the watch is to be assembled, knowing all the genes does not necessarily tell you how the organism is put together either, or how it may change over time or in response to outside influences. "For that we need to be able to build models, which we can then use to test predictions," said Ward. By the time systems biology comes of age, we may have learned a lot more physiology.
--Tom Fagan