Credit: © Nick Burchell In November 1998, Martin Burke was on his first clinical rotation in the MD/PhD program at Harvard Medical School when he met a 22-year-old cystic fibrosis patient who was taking 17 different medications. Knowing that a single missing chloride channel causes the disease, it bothered Burke that the treatment comprised such a large cocktai" /> Credit: © Nick Burchell In November 1998, Martin Burke was on his first clinical rotation in the MD/PhD program at Harvard Medical School when he met a 22-year-old cystic fibrosis patient who was taking 17 different medications. Knowing that a single missing chloride channel causes the disease, it bothered Burke that the treatment comprised such a large cocktai" />
Advertisement

Martin Burke: The smart synthesizer

Credit: © Nick Burchell" /> Credit: © Nick Burchell In November 1998, Martin Burke was on his first clinical rotation in the MD/PhD program at Harvard Medical School when he met a 22-year-old cystic fibrosis patient who was taking 17 different medications. Knowing that a single missing chloride channel causes the disease, it bothered Burke that the treatment comprised such a large cocktai

By | July 1, 2008

<figcaption> Credit: © Nick Burchell</figcaption>
Credit: © Nick Burchell

In November 1998, Martin Burke was on his first clinical rotation in the MD/PhD program at Harvard Medical School when he met a 22-year-old cystic fibrosis patient who was taking 17 different medications. Knowing that a single missing chloride channel causes the disease, it bothered Burke that the treatment comprised such a large cocktail of drugs. It struck him immediately that science might be able to replace the missing ion channel in the same way that a prosthetic limb replaces a lost leg. "I wanted to develop prostheses on the molecular scale," he says.

As far back as Burke can remember, he wanted to become either a major league baseball player or a doctor. Unfortunately, baseball didn't pan out. So, as an undergraduate at Johns Hopkins University in 1994, he enrolled in pre-med courses, including an introductory organic chemistry class that would change his life. There, he met Christina White, a chemistry graduate student and his teaching assistant. Two things from that class stuck with him: chemistry and Christina. He and White, both now assistant professors of chemistry at the University of Illinois, married in 1996.

Captivated by chemistry but still with an eye to therapeutic applications, Burke designed his own undergraduate research project. He split his time between Henry Brem's neurosurgery lab and Gary Posner's chemistry lab to develop biodegradable polymers that deliver vitamin D derivatives to the brain for tumor treatment. The project "was entirely from his own initiative," says Brem. "It was obvious even then that he was an off-the-scale, extraordinary person."

When Burke started graduate school at Harvard in 1998, most biologists used only small synthetic molecules to interfere with proteins. Burke, however, wanted to use these compounds to rebuild protein functions. Before he could achieve that goal though, he needed a more efficient way of making the molecules. He used the chemistry of aromatic furan rings to design multiple structural versions of molecular skeletons, the backbones of small-molecule synthesis. He combined this with conventional combinatorial approaches and created a library of 1,260 compounds in just five steps.1

Building on his success in the lab, Burke also helped develop a more general and systematic scheme for synthesizing small molecules.2 This approach, says Burke, can be used to rapidly generate thousands of compounds to screen for new drugs or as probes to understand protein function. "For a lot of us, chemistry is a tool," says Rahul Kohli, a biochemist at Johns Hopkins University and one of Burke's graduate school classmates. "But for Marty [Burke], chemistry is his passion."

After earning his PhD, Burke returned to medical school for two years of clinical rotations, but he realized that to achieve his visions of "molecular prostheses," he needed to devote himself entirely to research.

Since 2005, Burke has headed his own lab at the University of Illinois where he's been investigating a small molecule called amphotericin B, which is a natural bacterial product often used to treat fungal infections. Amphotericin B works by self-assembling into ion channels and integrating into lipid membranes. Burke hopes that by tinkering with amphotericin B, he might be able to replicate ion channels synthetically, and tailor them to treat specific diseases. To understand the molecule's chemical biology, he knocked out specific parts of the molecule,3 and he is developing new synthesizing strategies to build the molecule from scratch. Amphotericin B is "nature's way of telling us that small molecules have untapped potential," he says.

Advertisement

Follow The Scientist

icon-facebook icon-linkedin icon-twitter icon-vimeo icon-youtube
Advertisement

Stay Connected with The Scientist

  • icon-facebook The Scientist Magazine
  • icon-facebook The Scientist Careers
  • icon-facebook Neuroscience Research Techniques
  • icon-facebook Genetic Research Techniques
  • icon-facebook Cell Culture Techniques
  • icon-facebook Microbiology and Immunology
  • icon-facebook Cancer Research and Technology
  • icon-facebook Stem Cell and Regenerative Science
Advertisement
Eppendorf
Eppendorf
Advertisement
The Scientist
The Scientist
Life Technologies