HHMI Investigator's Approach Could Lead to Novel Drug Design, New Way to Generate Energy

PASADENA, Calif.--For anyone suffering from cystic fibrosis or AIDS, the bacterium Pseudomonas aeruginosa is bad news. While the organism is found everywhere--including in sediment on the ocean floor--it can cause lung infections in those with weak immune systems.

California Institute of Technology researcher Dianne Newman thinks her laboratory work could lead to ways of neutering the organism's threat to patients--and, at the same time, perhaps even hijack the microbe's internal chemistry for a novel method of energy generation.

This unlikely marriage of medical application and environmental engineering has won Newman one of this year's prestigious funding awards from the Howard Hughes Medical Institute. Newman, who is Caltech's Luce Assistant Professor of Geobiology and Environmental Science and Engineering, joins 42 other leading American researchers as this year's new crop of HHMI Investigators.

One of the most prestigious honors in the country for scientists involved in biomedicine, the grant is designed to provide a select group of individuals "with the freedom and flexibility they need in order to make lasting contributions to mankind," says Thomas R. Cech, the HHMI president.

Newman's approach toward the microbe is to exploit the manner in which it must generate energy through electron transfer reactions in order to survive. Scientists know the fine details of electron transfer about a few proteins involved in cellular energy generation, but not about the processing of redox-active small molecules produced by organisms such as Pseudomonas aeruginosa, Newman says. Progress could lead toward new insights about the function of these molecules in biofilms.

For the biomedical application, the work could determine if other discoveries in Newman's lab can be applied to understanding how electrons shuttle about in the course of the microbe's carrying on its life functions, and how these processes could be interfered with for novel treatments. With the new HHMI funding, Newman says she will be able to take full advantage of her collaborative work at the Jet Propulsion Laboratory--work that has already led to her codesigning a special apparatus for studying electron shuttling in biofilms.

A possible outcome of the research would be the demonstration that electron shuttles work in such a way that the human pathogen Pseudomonas aeruginosa could be attacked through rational drug design. In other words, new drugs might be specifically created to interfere with the way that electrons move around in the course of the bacterium's doing what it needs to do to remain alive. Such a drug would be a new type of antibiotic.

"It's hard to treat these bacterial infections with conventional antibiotics," Newman says. "Hopefully we can learn something about what these organisms need to live, and can develop a new way to interfere with it."

A fuller understanding of the bacterium's electron shuttling mechanism could also perhaps lead to a new type of energy production with a novel device called a "sediment fuel cell." These are devices that are planted in ocean sediment, with the anode side (the side from which electrons flow) buried beneath the surface, and the cathode side (to which electrons flow) above the sediment surface.

Because the Pseudomonas aeruginosa bacterium has been found in significant numbers in biofilms developing on marine cathodes, the fuel cell could possibly be designed in such a way that the organism's life functions could be tapped to catch the energy from the current flow. This research is already receiving DARPA funding, and Newman says that the additional HHMI funding should provide her with greater flexibility to understand the basic biology needed to make the fuel cells work.

Such a fuel cell would work like an underwater battery, with the bacteria ultimately providing a source of current by carrying on their life processes.

A nonprofit medical research organization, HHMI was established in 1953 by the aviator-industrialist Howard Hughes. The Institute, headquartered in Chevy Chase, Maryland, is one of the largest philanthropies in the world with an endowment of $12.8 billion at the close of its 2004 fiscal year. HHMI spent $573 million in support of biomedical research and $80 million for support of a variety of science education and other grants programs in fiscal 2004.