They don’t line up like Legos or brick blocks in a house that the big bad wolf can’t knock down. In fact, many proteins, which are at the heart of pathways that tell other parts of cells what to do, fold over on themselves.
In a healthy person, those folds follow certain patterns, helping to conduct a signal or start or end a process. In people who have diseases like Parkinson’s, Alzheimer’s, or Huntington’s disease, the proteins don’t fold properly, causing a range of problems.
As the director of the Laufer Center for Physical and Quantitative Biology, Ken Dill, who is also in the Chemistry Department at Stony Brook, is interested in developing tools and principals of protein folding, some of which may help provide a better understanding of health and disease and may lead to more effective approaches to drug delivery.
“What happens in Alzheimer’s and Parkinson’s is that the proteins all glom together,” Dill said. “When and how they form is of interest to us.”
The typical drug delivery process targets a particular site on a protein and plugs it up “like a cork in a wine bottle,” he said. With Parkinson’s, however, the proteins are all bound together, which leaves no particular place to find a tight binding site.
Dill works with biotechnology companies including Amgen and Genentech. These companies make proteins as drugs, as opposed to pharmaceutical companies, which often make chemicals as drugs.
“It’s complicated to make a protein as a drug,” he said. “When you take a biotechnology drug, if you want to inject a solution of proteins, you want to concentrate the proteins as much as possible.” Putting them together in such a large group, however, causes them to stick together, which limits the ability to make them effective once they’re inside the body.
His lab, which includes 13 people, explores questions of how to keep proteins from tangling up, which is a goal of biotechnology companies designing drug therapies.
Companies design drugs that kill most of the bacteria in a population, but there are some that survive. Those last cells multiply and continue to develop, sometimes without any known remedy.
Scientists and bacteria are locked in a struggle Dill said was like the phenomenon from the Red Queen in “Alice in Wonderland,” where each participant has to keep running just to stay in place. Jim Wang, a chemistry professor at Stony Brook and an affiliate at the Laufer Center, is directly engaged in studying this dynamic.
Stony Brook faculty members have appreciated Dill’s leadership. Dill is “transforming research in physical and quantitative biology at Stony Brook,” said Joshua Rest, an assistant professor in the Department of Ecology and Evolution who is affiliated with the Laufer Center. “Before [Dill] arrived, scientists from different departments working on quantitative approaches to biology weren’t always talking to each other and taking advantage of each other’s expertise in a systematic way.”
Rest credits Dill with developing a community of researchers from diverse fields. He said Dill led an effort to understand the fundamental factors that affect cellular growth rates. Rest called Dill a “science superstar.”
Dill became interested in protein folding over a quarter of a century ago. He was fascinated by the intellectual challenge of understanding such a fundamental problem in nature.
Dill said he feels privileged to work at a place like the Laufer Center, where he doesn’t have to focus as much on short-term payoffs, but can think about and go after longer-term, harder problems.
In addition to about a dozen affiliated faculty members, the Laufer Center includes Dill and Associate Director Carlos Simmerling, who is also in the chemistry department, and Sasha Levy, who arrived from Stanford at the beginning of November. The group will also add Gabor Balazsi, who is currently a professor at the University of Texas M.D. Anderson Cancer Center, in June.
Dill and his wife Jolanda Schreurs live in Port Jefferson. Their older son Tyler is in graduate school at the University of California at San Diego and is studying nanoengineering, while Ryan is at UCLA and is majoring in chemistry.
Prior to working at Stony Brook three years ago, Dill lived in the San Francisco area. He said he appreciates Long Island and the variety of seasons, including the fall foliage.
As for his work, Dill said he remains “at least as excited as ever before” about the opportunities, where he feels as if the Laufer Center enables him to “take his own little moon shots.”