Colleen Tobolic (PHY) helps her son Brandon on the pony ride at the Argonne-East's employee picnic July 10

Research reveals secrets of staph, anthrax

Andrzej Joachimiak (BIO) and colleagues at Argonne and the University of Chicago have determined the crystal structure of sortase B, an enzyme found in the bacteria that cause staph and anthrax. While an antibiotic is probably five to seven years away, the structure could provide the first clue in developing a treatment for the infections.

"It's a long process, but we need more antibiotics," Joachimiak said.

It took the researchers 21 days to build the three-dimensional model of sortase from the genome. Without the new technology available at Argonne's Structural Biology Center, including the Advanced Photon Source's powerful X-rays to illuminate the structures and the Midwest Center for Structural Genomics' robotic and automation facilities for protein expression, purification and crystallization, the process could have taken several months. Their work was published in the July 13 issue of Structure.

By analyzing genomes, Joachimiak tries to uncover information that will lead to structure-based or "rational" drug design. The problem is that researchers don't know what half the proteins coded by the genome do or how they work. He did not know the structure of sortase until a few months ago either.

Now that Joachimiak understands the enzyme, he hopes to find a way to stop it - or at least to slow it down. Sortase attaches proteins to the surface of bacterial pathogens. These proteins help the pathogens survive and flourish.

Bacteria like staph and anthrax need iron to function. But little free iron is available in the blood stream because most of it is bound in red blood cells. So the bacteria develop a mechanism to pry open the red blood cells, and these proteins help them.

"This is actually a very smart mechanism," Joachimiak said. The process is outlined in an article published in Science last year by Olaf Schneewind of the University of Chicago, which laid the groundwork for the sortase project.

The bacteria open the blood cell, bind the hemoglobin that contains heme (the iron-containing non-protein portion of the hemoglobin molecule), transport the heme, degrade the heme and then extract the iron.

Before the protein can bind the hemoglobin, it has to be attached to a specific position on the surface of the cell. The bacteria use a specific enzyme to accomplish this; in this case it is sortase.

"Sortase would be a good target for a drug, because if one can block the enzyme, it will not be able to attach these proteins to the surface and the bacteria would not be able to get iron from our bloodstream," Joachimiak said.

The paper that appears in Structure's July 13 issue looks at sortase from both staph and anthrax - more formally, Staphylococcus aureus, and Bacillus anthracis, and concludes that the two are similar. Both have the same catalytic amino acid triad with Cys, His and Asp residues present in both enzymes - which means the site of the enzyme-protein reaction is structurally identical in staph and anthrax. Only the location of one residue varies.

Joachimiak said the fact that they have the same triad is important. If the sortase active site is the same in both, it can be blocked with just one drug. Furthermore, versions of sortase are found in several other gram-positive bacteria. That means one drug could double up and target a variety of different bacteria. Also significant, the enzyme is found only in certain bacteria, meaning treatments that target it would not likely affect human enzymes.

Now that the structure is known, Joachimiak said the next step is to mimic the signal sequence, or peptide, in the protein with a drug that blocks the enzyme.

"We would like to design a drug that will look like the peptide, but will not be the peptide," he said. "Something else that will bind to the same site and make sure the enzyme is dead or inactive."

This step is based primarily on trial and error. However, if scientists know the structure, they can make a more educated guess.

"We need to study more proteins from these genomes to better understand their biology and therefore be able to treat them or control them," Joachimiak said. "We know so little so far."

Research continues at Argonne's Structural Biology Center where more than 530 structures have been determined. Nearly 150 protein structures have been determined at the Midwest Center for Structural Genomics and recorded with the International Protein Data Bank - that's more than any other structural genomics center.

Joachimiak's co-authors are colleagues R-g. Zhang, R-y. Wu and G. Joachimiak (all BIO) at Argonne and S.K. Mazmanian, D.M. Missiakas, P. Gornicki and Schneewind from the University of Chicago. The published research was supported by the National Institutes of Health Grants and the U.S. Department of Energy Office of Biological and Environmental Research.

French nuclear policy
is topic of colloquium

Régis P. Babinet, the counselor for nuclear energy in the French Embassy in Washington, will present "Nuclear Energy Policy in France: European Context and Environmental Issues" at a Director's Special Colloquium at Argonne-East Friday, July 23.

The talk will begin at 2 p.m. in the Building 402 Conference Center. All employees whose schedules permit are invited to attend.

Babinet will provide a global overview of France's nuclear policy and discuss its impact on the European community. He will also examine France's current and future plans for using mixed-oxide fuel and consider the environmental impact of that nation's recycling and reprocessing of spent fuel.

Babinet began his career as a nuclear physicist with the French Atomic Energy Commission in 1968. He later headed one of its leading departments studying material behavior, particularly effects related to aging, in the context of the nuclear industry. He also spent two years as a visiting scientist at the Lawrence Berkeley Laboratory in California.

Continuous shuttle service will be provided from the 300 area and Buildings 208, 200, 205, 212, 201, 203, 222, 223 and 202 starting at 1:30 p.m. There will be one stop at Building 900 at 1:15 p.m.

Teachers, students to benefit
from science education initiative

U.S. Secretary of Energy Spencer Abraham recently announced a new initiative launched by DOE and its national laboratories to promote science education and help prepare the next generation of scientists and engineers.

"It is critical," Abraham said, "that we leverage the tremendous scientific resources of the Department of Energy and all of our national labs to help create a new generation of scientists who will achieve the scientific breakthroughs and technological advances that are essential to our future security and prosperity."

The science education initiative - called STARS, for Scientists Teaching and Reaching Students - will focus on several key areas involving partnerships and educational opportunities between DOE labs such as Argonne and teachers and students from elementary through high school. The program will provide hands-on training for teachers and educational opportunities for students, including career days, professional development programs and an annual science conference bringing together teachers, students, scientists and corporate innovators.

"Argonne and the other Department of Energy laboratories contain opportunities and facilities for researchers across the spectrum of science," said Argonne director Hermann Grunder. "Secretary Abraham's new science education initiative expands the offerings at Argonne and the other labs to students and teachers."

Argonne programs - ranging from internships for undergraduate and graduate students to hands-on training and research opportunities for science teachers to day-long programs for high school students, provide - ways for teachers to better teach and students to better learn.

DOE's new program, Grunder said, also strengthens Web-based science education, and Argonne's "Ask a Scientist" offering on the Web has for several years provided answers from scientists to students' questions.

"If we can spark an interest in science that leads a child to a career as a scientist or engineer," Grunder said, "we'll take great pride in that accomplishment. It's an important responsibility, and we welcome the Secretary's moves to enrich and broaden partnerships and educational opportunities between our labs, teachers and students from elementary through high school."

University shuttle bus schedule revised

The Argonne-University of Chicago Shuttle Bus schedule has been revised, with new dropoff and pickup times.

The full schedule is posted online.

Surviving summer,
quitting smoking topic of talks

The Argonne Medical Department will sponsor lectures on summer health and smoking cessation at Argonne-East during August. The lectures are free and registration is not necessary.

Physician Jami Stalker (HR-MD) will present "Is It Safe to Go Outside? A Summer Survival Guide," Wednesday, Aug. 4, at noon in the Building 213 Cafeteria, Dining Rooms A and B. The talk will focus on heat, sunburn, bugs, bee stings, poison ivy and storms.

"Smoking Cessation" will be presented by R. Michael Trapp, a licensed clinical professional counselor and certified alcohol and drug counselor, Thursday, Aug. 5, from noon to 1 p.m. in the Building 200 Auditorium.

Telephone seminar
can help tackle stress

A seminar on dealing with stress will be offered via telephone to Argonne employees by Cigna Behavioral Health starting at noon Wednesday, July 21.

"Stress and Our Perceptions" will focus on employees' choices in dealing with stress and how to take control of thoughts and actions.

Participants in the telephone seminar download PowerPoint presentations and handouts from a dedicated Web site at the time they pre-register. Participants call a toll-free number and listen to a recording of the seminar, which will be available for five calendar days.

Online pre-registration is required (See "On the Web," page X). Call-in numbers will be provided in the registration confirmation e-mail.

Upcoming telephone seminars include:

Wednesday, Aug. 18 - "Making Anger Work for You, Not Against You"

Wednesday, Sept. 22 - "Caring for Your Aging Parents"

Wednesday, Oct. 20 - "Your Attitude: Learned Optimism"

Wednesday, Nov. 17 - "Conquering the Winter Blues"

All seminars begin at noon and online pre-registration is required.

Ask the Directorate

Q. I enjoy the Lab Director's special colloquium series but sometimes can't attend due to work responsibilities. However, if the seminars were broadcast on the Argonne Web site, I would often be able to listen. Also, visitors to the Argonne Web site would have access, which would be a public service. Is there any chance the audio feed of these special colloquia could be accessed on the Argonne Web site and after the colloquium the audio file could also be accessible for a period of time?

A. These are excellent suggestions and we are looking into making them happen. Certainly, the technology exists so the question is one of cost. We will keep you advised.

In the meantime, each of the colloquia is videotaped, and copies are available to all Argonne employees from the library in Building 223, starting about a week after each presentation.

CIS classes

Full Computing and Instrumentation Solutions computer class descriptions, schedules and enrollment forms are available online. Unless otherwise specified, classes take place in Argonne-East's Building 201, Room 167, are limited to eight participants, and cost $215. For more information, contact Diane Cavazos at ext. 2-7153 or dkcavazos@anl.gov.

August classes include:

"Intermediate Access 2002" (CIS117) - Wednesday, Aug. 4, 8:30 a.m. - 4:30 p.m. Prerequisite: "Introduction to Access 2002."

"Intermediate Word 2002" (CIS115) - Monday, Aug 2, 8:30 a.m. - 4:30 p.m. Prerequisite: "Introduction to Word 2002."

"Intermediate Excel 2002" (CIS116) - Tuesday, August 3, 8:30 a.m. - 4:30 p.m. Prerequisite: "Introduction to Excel 2002."

"Introduction to PowerPoint 2002" (CIS114) - Thursday, August 5, 8:30 a.m. - 4:30 p.m. Prerequisite: An understanding of Windows.

"Advanced PowerPoint 2002" (CIS118) - Friday, August 6, 8:30 a.m. - 4:30 p.m. Prerequisite: "Introduction to PowerPoint 2002."

"Beginning Unix" (CIS564) - This class consists of two three-hour sessions for a total of six hours First session: Tuesday, July 20, 9 a.m. - noon. Second session: Thursday, July 22, 9 a.m. noon. There is no charge for this class.

"vi Editor in Unix" (CIS567) - Friday July 23, 9 a.m. - noon. Prerequisite: A general knowledge of Unix, especially Unix file management commands. There is no charge for this class.