E. coli and S. aureus are often linked to scary headlines about antibiotic resistance or food contamination. But some strains of these common bacteria hold clues to cleaning up toxic wastes laced with mercury.

The detoxification process requires an enzyme called mercuric ion reductase, so far found only in microbes. Susan Miller, a pharmaceutical chemist in the UCSF School of Pharmacy, studies the activity and structure of this catalytic enzyme to discover how it converts toxic mercury into a less threatening form, which then diffuses harmlessly out of the bacterial cells.

With some of the key features already outlined, her laboratory is launching efforts to redesign the enzyme to convert other toxic ions, such as chromium or uranium, into forms less harmful to the environment. Chromium dumped by power plants — famously brought to light by Erin Brockovich — has polluted many underground water supplies in the US. Uranium pollution plagues deactivated nuclear weapons facilities.

The bacteria most likely inherited their impressive abilities from other microbes that evolved in high-mercury environments. Surprisingly, the hardy species were not discovered in a toxic dump or near a poisonous volcanic plume, but in hospitals where mercuric antiseptics were used to kill bacteria. "When researchers tried to confirm that the antiseptic had killed all the bacteria, they found these mercury-resistant species were thriving," Miller says.

In the process of detoxifying mercury, the catalyst transports the metal ions from its own surface to a "buried" active site within it, Miller says. There, each ion gains two electrons — a process known as a reduction, since the net charge is reduced — to become stable, elemental mercury. She thinks the catalyst's powers lie in its structural traits: whether it's rigid or bendable, or what other molecules it attracts, for example.

"In the core of the protein, where the reduction takes place, part of the protein looks like a tail, and we think its motion may be crucial to the process," she says.

Since Miller moved into Genentech Hall in January 2003, her ability to test this hypothesis has been given a major boost. She is collaborating with a colleague in her "neighborhood" — one of the building's fourteen clusters of faculty scientists and their laboratories, intended to spur such partnerships.

"We're interested in the mechanisms that different structural features allow, and Volker Doetsch is an expert at determining protein structure, so it's not just helpful but exciting to have Volker and his lab next door," Miller says.

The move to Genentech Hall came ten years to the month after Miller arrived at UCSF as an assistant professor in 1993. Her focus on protein structure stems from a lifelong interest in taking things apart and putting them back together to see how they work.

Temperamentally part engineer and part lab director, she enjoys taking apart and reassembling her own lab equipment. "When an instrument isn't working in the lab, I'm usually the one who can take it apart and figure out where the problem lies." And she has surprised more than one grad student who caught her in the lab at odd hours doing experiments.

"One of my heroes was my postdoc advisor at the University of Michigan. He died recently at 75, but he was in the lab doing experiments two days before. That endless curiosity and inquisitive spirit is inspirational to me."

Miller likes to spend time away from the lab with her 16-year-old daughter and her husband — when he's in town. "He's a chemist too, but also a CEO," she explains. Since she lives across the Bay in the Oakland hills, the Mission Bay campus is more convenient than Parnassus. But it has not all been smooth sailing. "This semester I teach a pharmaceutical chemistry course three mornings a week at 8 a.m. at Parnassus, so I go from Oakland to Parnassus to Mission Bay. I'm still feeling like a guinea pig. But it's very exciting to be here."

Source: Wallace Ravven

Last updated January 28, 2005

Susan Miller

Susan Miller. Photo by Majed.