Biology's big tent

Christopher Love Age: 30 Bachelor's degree: Chemistry, University of Virginia Photo: Kim Furnald

When Christopher Love started his postdoctoral fellowship in the immunology research group of Whitehead Member Hidde Ploegh, he had not taken a biology class since high school.

Love knew how to make magnetic nanoparticles organize themselves into microscale structures and how to create nanometer-thin crystalline coatings of molecules on metals. He wanted to apply such tools from the physical sciences to advance medical knowledge and public health.

Jumping feet-first into a biology lab, he figured, was his best chance to bridge the gap. From the perspective of a surface chemist, immunology seemed the easiest entry point. “I knew there was a lot of contact between cells and that it involved surface interactions— something familiar,” Love says. “It took me a year to understand the terminology. It’s a different language from even other areas of biology.”

He needed even more time to understand how biologists think. “Biology has an extra level of complexity from materials science, physics and chemistry,” Love comments. “I’m amazed at the types of insights biologists can draw from experiments, where it tends to be difficult to control the variables.”

Shawdee Eshghi Age: 30 Bachelor's degree: Chemical engineering, MIT Photo: Kim Furnald

In a recent meeting of the Harvey Lodish lab, discussion turned to the evolution of red blood cells: Why does a red blood cell lack a nucleus?

“The first thing I thought of was the mechanical properties of the cell,” says Shawdee Eshghi, who is just finishing her doctoral work in biological engineering under the joint oversight of Lodish and Linda Griffith in the MIT biological engineering division. “The nucleus is stiff and cannot bend. The hallmark of the red blood cell is its flexibility. That’s not what comes to the minds of most biologists.”

Engineers and biologists think differently. “In engineering, you start with physical laws you know are irrefutable, and if the data don’t support them, you know that the data are wrong,” Eshghi says. “In biology, you don’t have that starting point. It’s very empirical. Classical biology papers use a lot of inductive reasoning: ‘This is our hypothesis. Here are some data to support it. Maybe this is what’s going on. We did another experiment to show this isn’t it.’ They present all the hypotheses and knock them down.”

She adds that engineers have a versatile common language: mathematics. But biological systems need more levels of explanation.

Danielle Cook France Age: 28 Bachelor's degree: Biomedical engineering, Washington Univ. Photo: Kim Furnald

A biologist can be hard to find in the Whitehead lab of Paul Matsudaira. And the lab’s expertise ranges from simulating colliding stars on super-computers to building joints for robotic arms.

“I wish we could get a biology graduate student to work on Vorticella,” a genus of protozoa, muses Danielle Cook France. “There are tons of open questions.” In the meantime, lab technicians provide the biological expertise and tutoring in protein purification.

France, a biological engineering graduate student, studies the rubber-band-like properties of the stretchy stalk that affixes the tiny pond critter to a rock or crustacean. When she publishes papers, she considers which community she wants to reach, either cell biologists for the subject matter or biophysicists for the underlying imaging. “People either peg you as a biologist or an engineer,” she says.

France, whose mom is a math teacher, set her sights on engineering earlier than most girls. “I see a lot of future in using the biology we know to engineer new things, such as building materials from basic biological components,” she notes. “MIT has given me more confidence about starting my own company. That spirit is in the air.”

Kyle Farh Age: 28 Bachelor's degree: Computer science, Rice Univ. Photo: Kim Furnald

Kyle Farh’s computer science training brings much-needed expertise to the Whitehead lab of David Bartel. But it did not help during his first two years at Harvard Medical School.

“I probably went to medical school knowing the least molecular biology of all my classmates,” remarks Farh, who initially joined a dot.com startup company after college.

At Whitehead, Farh’s bench work remains limited to occasional and relatively simple procedures. He has surrounded himself with experimentalists who inform and inspire his computational inquiries. Recently, Farh and collaborator Andrew Grimson found that mammalian genes have evolved to avoid targeting by microRNAs that would otherwise reduce or compromise the genes’ function.

For all the differences, Farh has found a lot of common ground between computational and experimental biology. “The thing that biologists are really good at, compared to other scientists, is doing controls, because there is so much you don’t know about the system, which is so complex,” Farh comments. “You really have to be as rigorous about controls in computation.” In the end, he says, test results can be equally enlightening or enigmatic.