November 7, 2003

Shedding Light on Disease

A group of four Brookhaven Lab scientists investigating the underpinnings of diseases from osteoporosis to botulism presented an overview of their work to a group of reporters in person and via live webcast on Thursday, October 23, at the Lab. All the presenters use the extremely bright beams of energy (from infrared to x-rays) available at the National Synchrotron Light Source (NSLS), one of the Lab's premiere research facilities.

Light Source Chair Steven Dierker gave an overview of the facility, which is used by more than 2,500 scientists from outside the lab each year including this year¹s chemistry Nobel Prize-winner, Rod MacKinnon of the Rockefeller University, who used x-rays to determine the structure of proteins that help transmit nerve impulses throughout the body. Solving protein structures via the technique of x-ray crystallography can help scientists understand their functions and perhaps devise strategies to prevent these proteins from causing disease.

That's the exact approach being pursued by Brookhaven biologists Walter Mangel and Subramanyam Swaminathan. Through x-ray crystallography and other techniques, Mangel has uncovered several parts of a viral enzyme that might be susceptible to antiviral drugs. If you can block the activity of the enzyme, he says, you can block the infection.

What's more, the sites he's identified interact with one another. This led Mangel to propose a new type of multi-drug therapy that viruses wouldn't be able to outsmart via evolution of drug resistance. Using multiple drugs against several targets on the same enzyme might be effective against a range of viruses, including those that cause pink eye and AIDS, and against a range of bacteria, including those that cause Chlamydia, plague, and even malaria.

Swaminathan is using the NSLS x-rays to reveal components of botulinum toxin, the protein that causes botulism, that are central to its paralyzing effects. He¹s working to develop drugs that fit into the toxin¹s active sites to disrupt the potentially deadly process at three crucial steps. The result may be a vaccine and/or drugs that eliminate the toxin¹s potential as an agent of biowarfare or bioterrorism.

Shining the NSLS's beams on more traditional targets ‹ bones and other body tissues ‹ are Brookhaven biophysicist Lisa Miller and physicist Zhong Zhong. Miller is using the infrared beams to study bone composition, particularly that associated with areas of
microscopic damage. She wants to know how bone composition changes in response to common osteoporosis treatments. Her work could lead to improvements in osteoporosis drugs.

Zhong uses the NSLS x-rays to look not just at bone but at soft tissues like cartilage, blood vessels, skin, and fat deposits as well. His technique, called diffraction-enhanced imaging (DEI), uses higher energy x-rays that pass right through the sample without being absorbed, which results in a lower dose to the patient than traditional x-ray techniques. DEI makes soft tissues visible because each tissue type scatters the beam differently. A sensitive analyzer crystal can detect these subtle diffractions and translate them to different intensities, visible on x-ray film in magnificent detail. The technique could yield more accurate and earlier diagnosis of soft-tissue diseases such as breast cancer.

If you want to see the scientific talks, you can visit our video archive at www.bnl.gov/video. The presenters' slides are available there for downloading as well.

PHOTOS BY: Roger Stoutenburgh