Web Exclusives: Interview

Q&A: Ravi Iyengar on Molecular Systems
By Emily Carlson
Posted March 30, 2009

Ravi Iyengar likes listening to music—Indian, classical, opera—but he says his favorite hobby is science. Good thing it’s also his full-time job. Trained as a biochemist, Iyengar has spent much of his career studying molecules and developing a list of all the parts that help a cell function. A professor at Mt. Sinai School of Medicine in New York, he is now committed to figuring out how and why those parts work together.

Biochemist Ravi Iyengar compares himself to a furniture maker. But instead of assembling small parts to make a table or cabinet, he’s putting together biological systems to understand how they function.

I talked to him about his work and his systems biology approach.

What is systems biology?
Systems biology is a holistic way of studying biology at any level—molecular, cellular, individual organism or groups of organisms. You look at things as a whole in the context of many components and how they interact.

Is systems biology a new field?
People have been studying systems for a long time. Physiology is a classical example of an area that uses systems approaches. However, in the past [researchers] have not been able to understand relationships between the different levels of organization. Fifty years ago when people studied heart rate or brain waves, they did not have an understanding of what molecules and genes were involved or why those [rhythms] existed. Now we do.

What system are you studying?
I largely study things at the cellular level—how molecules come together to form cells and how cells behave like molecular societies. We use neurons, kidneys cells and skin cells in our studies.

Why is it important to understand how these interactions begin, evolve or change?
Often diseases originate because a certain molecule or a group of molecules are “bad” and the interactions changed. Cancer and heart disease are good examples of such diseases.

You need to understand the system as whole to understand why a drug works, and you need to know the molecular details to design those drugs. A good example of this is cancer: All new cancer drugs work on the molecules that, due to mutations or other changes, make tumors grow.

What’s the role of computation in piecing together the components of biological systems?
Biological systems, such as a cell with cancer genes, have more interacting parts than the mind can grasp on its own. Computation allows us to put them all together. If you go to the store and buy milk and orange juice, you don’t need a calculator to know the total cost. But if you want to buy 22 items, adding the numbers is a lot easier with a calculator. Computation also helps you analyze different choices. If you want to splurge on something but stay in your budget, then you have to make certain choices, like buy store brands. In both these ways, computation enables us to go through large systems in a pretty fast way to generate hypotheses of how those systems might work and how we can predict [their] behavior.

What has your research revealed about molecular and cellular systems?
Our studies have shown how connecting many chemical reactions together produces cellular memory. A neuron may remember a certain stimulus or an immune cell may remember a foreign object and secrete an antibody. The other major finding from these systems biology studies is that balance between molecules and reactions is essential for a cell to stay active, behave, learn or live.

How did you become a systems biologist?
My background is in studying molecules—one type at a time and in great depth. When I became a biochemist 30 years ago, we needed to know details about individual molecules. As we gathered more and more information, we needed to understand how [the molecules] came together to form functional systems.

If you’re a furniture maker, you might spend a long time building a little wooden screw or a hidden joint that works really well. Once you build those little parts, you want to put them together with other parts to build a cabinet or a table. As a craftsman—or a scientist—you always take what you do to the next level. Rather than building parts, we identify and study the parts nature has built.

Why did you initially pursue a career in science?
I always wanted to do something that would be interesting. Every day when I come to the laboratory, there is always something new and different. Science really challenges your mind and always keeps you interested. There’s never a dull day.

What do you tell students who are interested in systems biology?
I tell them it is a great area of study to get into. Here are three reasons why.

1. A few years ago, there was no Twitter. Five years ago, there was no YouTube. These types of cutting-edge technologies bring individuals together across societies. Similarly cutting-edge technologies in computer science, microscopy, biochemistry and molecular biology drive connections and obtaining new knowledge. These technologies are really a lot of fun to work with.
2. Systems biology makes us think quantitatively. Already a quantitative way of thinking is becoming a very intrinsic part of our lives. Hardly anyone buys an airline ticket without going to Kayak^TM or some other site to compare prices—this is thinking both at a systems level (a system of all the airlines) and quantitatively (price differences between tickets).
3. Just as physics and chemistry drove industrial development during the last century, all the stuff we’re doing in biology and systems biology is going to drive industry in the 21st century. Students will have great career options in a number of industries as well as academia.