By Nancy Ross-Flanigan
News Service

What does it mean to be alive? Surely science has a succinct answer to such a fundamental question.

“Actually, no,” says chemistry professor Nils Walter. “In spite of impressive advances in our knowledge of basic biological processes, some major gaps exist in understanding how all the pieces fit together.” A new center opening soon on campus under Walter’s direction aims to provide researchers with the equipment and expertise they need to start filling in some of those gaps.

The Single Molecule Analysis in Real Time (SMART) Center, located in recently renovated space in the biophysics area of the Chemistry Building, will bring together basic scientists, engineers and clinical researchers to explore the emerging field of single-molecule science.

With motion-detecting microscopes that spy on interactions between drug-laden nanoparticles and membranes in living cells, fluorescent tags that make enzymes glow like neon when they change shape, and laser beams that act like miniature tweezers — tugging on molecules to turn genes on and off — scientists will probe the behavior and properties of individual molecules. Then they will apply what they learn to some of the most pressing questions in biology, medicine and nanotechnology.

Just as the personality quirks and distinctive looks of individual people are lost in descriptions of “average” behavior and appearance, the idiosyncrasies of individual cells — and the molecules that make them up — are lost in approaches that look at ensembles of cells. The single-molecule approach zeroes in on the relatively small number of like molecules active in a single living cell (or nanotechnological device) at any given time, looking at how many of each type of molecule are present, where they are located and how strongly they interact with their partners.

With such information, scientists not only gain a critical, global view of how the combined behavior of all these molecules translates into properties of a living cell, but they also can model that behavior and predict how adding something to the system — say, a particular drug — might affect the cell as a whole.

“In a way,” Walter says, “single-molecule studies finally get down to the same level as nature itself, allowing us to directly see biochemical processes of life that were invisible before.”

Single-molecule science is not new to U-M; for some time, individual research groups scattered around campus have been pursuing individual projects. But not everyone has had access to the necessary tools and know-how, and among those who have, exchange of information and ideas has been sporadic. Then, in 2006, a group of researchers held a Single Molecule Symposium to share knowledge and raise awareness of the power of these techniques.

“We had about 200 participants just from U-M — a strong indication of interest,” says Jens-Christian Meiners, associate professor of physics and director of the biophysics program. “But while there was great interest, there were also barriers to entry in the field. It sounds so easy to do — you just take a molecule, you look at it, you pull on it — but there are a lot of technical obstacles, like how to keep your molecules from sticking to the surface or how to keep your fluorescent tags from bleaching, that aren’t always addressed in published experiments. Sometimes there’s a little bit of black magic involved in how to make it work, which makes it hard for a research group that just wants to use these techniques to answer one particular question.”

That’s where the center comes in. “We’re bringing together all the brain power and technological expertise to create a resource for researchers on campus and from other institutions,” Walter says.

Even before its official opening, scheduled for April 4, the center — funded in part through the American Recovery and Reinvestment Act — already has helped attract new faculty to work at U-M, Meiners says. Current faculty, even those already involved in single-molecule science, also see the value of the center.

“State-of-the-art equipment is expensive, and its maintenance isn’t trivial. The experiments aren’t trivial to run, either, so some things are best done in a center instead of in a whole slew of individual labs,” says Mark Banaszak Holl, associate vice president for research and professor of chemistry and of macromolecular science and engineering. His research focuses on how nanoparticles interact with cell membranes and how those interactions affect gene expression. “For the kinds of studies we need to do, we really need that capability.”

The SMART Center’s lab director, Tristan Tabouillot, has been meeting with research groups around campus to find out what equipment they already have and what they might need the center to provide. Eventually, the center will reach out to researchers at other universities, offering them opportunities for training and use of the equipment.

Walter also has plans for student exchanges with other Michigan colleges and universities, as well as a “Single Molecule Roadshow” designed to introduce high school students to single-molecule science.

“We’re creating an invaluable, one-of-a-kind resource here at the University of Michigan with which we expect to push the envelope of what’s possible today,” he says, “and in typical Michigan fashion, we’re eager to share it with the world.”

Copyright 2009 Regents of the University of Michigan