Jeanne Hardy
Department of Chemistry, University of Massachusetts, Amherst
Stalking Suspects in the Chem Lab
Jeanne Hardy sees more in a crime-scene mystery than just a good read. For her, it can be a chemistry assignment, to pull her students into the thick of atoms and molecules. As it turns out, her own work this year would make a lively mystery story all its own.
Here's a possible chapter title, for a tale about pharmaceuticals and disease: "How Did the Protein Chemist Nail Exactly the Right Suspect?"
In both crime and biochemistry, that process is called target validation. A first step is to rule out the wrong options as you narrow the search for a target protein to cure a disease, like Parkinson's.
Her work will draw on skills from her background in the drug industry, at Sunesis Pharmaceuticals Inc., in South San Francisco, during an NIH-funded post doc, before she joined the Department of Chemistry at the University of Massachusetts Amherst. She still calls herself an expert protein crystallographer.
In her lab on the 10th floor of Lederle Graduate Research Tower, with a view of the Amherst College spire and the Connecticut River, she and her team of eight students and two post-docs will construct biochemical devices to turn on and off the function of proteins. These devices, called allosteric switches, focus on the cavities in proteins, reshaping them so that a molecule will bind there. Such binding is how a drug works, switching off the function of a protein.
In the past, she has worked on a group of potential targets called caspase proteins, a dozen of them in all. They play a role with autoimmune diseases and tumors. With her Cottrell Grant, she aims to tackle a class of enzymes called phosphatases, with about 100 family members. "You can't know which one serves a particular function in causing a disease until you switch it off," she said. To accomplish that, they'll devise chemical switches for each one in order to study their potential roles in disease.
These proteins are too small to photograph using light, but she can photograph them using a picture of the effect the atoms have on X-rays, making a diffraction picture. Then she can construct a three-dimensional model, showing where all the atoms fit. And with that, she can figure ways to substitute new atoms within the protein.
In the teaching component of her Cottrell Grant, Hardy hopes students will see the adventure in all this chemistry. She plans to attract nonscience majors with advertisements in city buses promoting CSI-type crime scene exercises.
And they may learn to see even more.
Hardy, who spent a year in Japan after getting her Ph.D. at Berkeley in molecular and cellular biology, relishes yoga and lets it frame her world, even the proteins. "Yoga is movement, and proteins move about too," she says. "It's like they are doing a form of yoga.
"We move the body into interesting positions," she says, "and in reality, proteins move a lot too. They jiggle around, doing microscopic motions in their domain. Proteins can do what looks almost like a yoga move, reaching, trying to touch their back."
But you must look carefully. A protein is tiny indeed. And Hardy may the only person who can appreciate the beauty in the kind of yoga done by molecules.
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