SARS SNAPSHOT — Researchers from the Structural GenomiX company used the powerful X-rays at the Advanced Photon Source to determine the first structure of the main protease from the coronavirus that causes Severe Acute Respiratory Syndrome (SARS). A protease is a viral enzyme critical in the SARS life cycle.

SARS protease structure determined at APS

By Evelyn Brown

Researchers from a California company using the powerful X-rays at the Advanced Photon Source have determined the first structure of the main protease from the coronavirus that causes Severe Acute Respiratory Syndrome (SARS). A protease is a viral enzyme critical in the SARS life cycle.

The scientists from Structural GenomiX created a three-dimensional, high-resolution image of a crystal of the SARS virus, which will be useful to researchers developing a drug to inhibit the SARS virus replication. A similar strategy succeeded with the human immunodeficiency virus protease for treatment of AIDS.

Structural GenomiX is a San Diego-based company that operates a macromolecular X-ray diffraction beamline at the APS, the Western hemisphere’s most brilliant source of X-rays for research. The company uses the X-rays to reveal, in atomic detail, how small molecules interact with drug targets in structure-guided drug design.

Because of the serious public health issue posed by SARS, Structural GenomiX deposited the crystal structure in the Protein Data Bank, a public database available to researchers worldwide, before publishing a paper in a refereed scientific journal. The company is exploring collaborative opportunities to develop a treatment.

With the experimental structure and an ample supply of crystals of the SARS main protease in hand, the company can now conduct experiments to determine the structure of the site where the protease creates infectious particles -- the protease-inhibitor complex -- and to create a drug molecule that fits in the active site to block this step.

Structural GenomiX used its proprietary process to create the crystal and the company’s X-ray data collection facility at the APS to determine the protease’s crystal structure at a resolution of 1.86 Angstroms -- less than one atom’s width.

They determined the crystal structure in a little more than one month after receiving cDNA clones from the Genome Institute of Singapore. The typical timeframe for this is usually months or years.

“SARS has been labeled the first 21st century epidemic,” said Joshua Lederberg, president emeritus of The Rockefeller University, Nobel Laureate, and an expert in antiviral research.

Structural GenomiX is setting an example by sharing this structure with the research world to speed drug development in case SARS recurs, Lederberg said.

Argonne joins new center for disease studies

Argonne will join the University of Chicago, Northwestern University and 11 other upper-Midwestern universities, hospitals and research organizations in a Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research.

The National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health, selected the collaboration of 14 Midwestern institutions for the regional center. The U.S. Department of Health and Human Services, NIAID’s parent agency, announced the selection in Washington, D.C. Sept. 4.

With funding of more than $7 million a year for five years, the Midwestern Regional Center of Excellence (RCE) will apply the tools of modern science to mankind’s age-old battle against infectious disease. NIAID plans to invest approximately $350 million over five years in eight such centers around the country.

The Midwestern RCE will be headed by Olaf Schneewind, professor of molecular genetics and cell biology and chair of the committee on microbiology at the University of Chicago, and Robert Murphy, the John P. Phair professor of infectious diseases at Northwestern University Medical School.

“While this project has been driven by recent concerns about bioterrorism, the knowledge we will gain from it could have a significant impact on humanity’s eternal battle against all infectious diseases,” said Schneewind. “The NIH is placing high priority on research on the diseases caused by organisms that could be used as bioterror agents, as well as diseases that are emerging or re-emerging threats to public health.”

The strength of the Midwestern RCE is in the quality and diversity of its member institutions and scientists, said Murphy.

“Together we will be able to pool our resources and develop novel diagnostic tests, vaccines and treatments against the agents of bioterrorism and emerging infections, such as SARS,” Murphy said.

The regional centers are a key element in NIAID’s strategic plan to expand research in the detection, prevention and treatment of potentially lethal illnesses that can be caused by biological agents. These range from the known pathogens that could be used for bioterrorism to new and as yet little-known emerging diseases that develop naturally, such as SARS, West Nile virus, drug-resistant bacteria and many others.

The Midwestern RCE will focus on the development of diagnostic, therapeutic and vaccine products for anthrax, botulism, tularemia, plague and hemorrhagic fever viruses. Such research, based on genomics, proteomics and a molecular-level understanding of cell function, is expected to have profound and far-reaching consequences over the next decade and beyond.

“Much of what we know about the biology of our own cells comes from the study of microbes that disrupt those processes,” said James Madara, dean of the division of the biological sciences and the Pritzker School of Medicine at the University of Chicago. “What better way to learn more than to focus on the organisms that have the maximum effect on those critical cellular pathways?”

The Midwestern RCE pulls together research teams from 14 institutions in the six states included in the federally designated Region V. The research teams will involve more than 300 scientists, said Schneewind, including a core of more than 60 key researchers who specialize in microbiology, infectious diseases, public health, medicine, vaccine research and pharmacology, as well as related disciplines such as biochemistry, computer science, engineering, mathematics and nanotechnology.

The RCE will act as a regional resource for public health officials, providing expertise, rapid diagnosis, support and advice about containment and treatment in the event of a bioterror outbreak or the emergence of new disease-causing agents. It also will teach young scientists and technicians how to do productive and safe research on infectious disease.

Center’s support lab may be sited at ANL-E

The University of Chicago has applied for a grant of more than $20 million to construct a facility that would support the entire Midwestern Regional Center of Excellence. If funded, this 54,100 square-foot Regional Biocontainment Laboratory would be located at Argonne.

The regional laboratory would be designed to safely conduct research on a large scale involving microbes that cause diseases such as anthrax, botulism and plague.

The location provides the advantage of proximity to Argonne’s facilities for computation, structural biology and observation, and easy access to the Advanced Photon Source, the most brilliant source of hard X-rays for research in the Western Hemisphere. An announcement about laboratory funding is expected within a few weeks.

Auciello honored for thin films

By Rhianna Wisniewski

Senior Scientist Orlando Auciello (MSD) recently received two prestigious awards for his technical accomplishments with thin film science and technology.

He received the Outstanding Technical Achievement Award from the Hispanic Engineer National Achievement Award Corporation (HENAAC), recognizing the contributions of outstanding Hispanic-American science, engineering and technology professionals.

The recent work by Auciello and colleagues (John A. Carlisle and Dieter M. Gruen, MSD; and Ralf and Hildegard Spitzel from Innovative Plasma Systems, Cologne-Germany) on the Large-Area Ultrananocrystalline Diamond (UNCD) Film and Deposition System also earned an R&D 100 award, which highlights the best products and technologies worldwide as judged by R&D magazine.

UNCD films exhibit a unique microstructure with diamond grains three to five nanometers in size that yield a unique combination of mechanical, tribological, electronic, chemical and biocompatible properties that can be extended to large-area coatings suitable for making macro-devices, microelectromechanical systems and nanoelectromechanical system devices, biodevices and biosensors.

“I feel recognized,” Auciello said. “Winning these awards makes me feel good, but humble, since these are not only my achievements. These awards are really dependent on a great team that includes my colleagues and bright and hard-working students and postdocs.”

Auciello’s current work focuses on both thin oxide and diamond films. One application of his work on oxide ferroelectric films is “smart cards” -- cards with a built-in microchip based on revolutionary ferroelectric random access memory (FeRAMs) that can store information without the need for a battery back-up. High-density FeRAMs may replace DRAM and Flash memories that now dominate the memory market.

UNCD films may be used to produce implantable biodevices such as artificial retinas to restore sight to people blinded by retina degeneration, or high-sensitivity biosensors to help detect dangerous chemicals.

“Cantilevers made with UNCD films vibrate and the vibrations can change when biomolecules attach to the surface of the UNCD film-based cantilever,” he explained. “This could provide the base for a biosensor.”

Soon to come may be tiny syringes to inject drugs. One example of this technology could be a small device that tests and automatically injects diabetics with insulin when needed.

Winners of 2003 HENAAC awards will be honored at the HENAAC Awards Ceremony Oct. 17.

Employees at both sites asked to donate blood

Blood drives are planned for both Argonne sites in coming weeks.

The Medical Department at Argonne-East will hold its fall blood drive Wednesday, Sept. 24, in the lower level of Building 617. This bi-annual drive, which will take place from 8 a.m. to 1:45 p.m., features a random drawing for two tickets to see the Chicago Bears. Anyone who donates blood is eligible to enter the drawing. Winners will be drawn periodically throughout the season.

Employees at Argonne-West can also become volunteer donors by participating in the American Red Cross Blood Drive on Wednesday, Sept. 17. Those who wish to do so should report to the Idaho National Engineering and Environmental Laboratory Fire Station from 10 a.m. to 2 p.m. Please call ext. 3-7341 for more information or to schedule an appointment.

According to the American Red Cross, only five percent of Americans are regular blood donors, despite a chronic blood shortage. Participants in last April’s blood drive at Argonne-East donated enough blood to save the lives of more than 231 patients.

For more information on the blood donation process, visit the American Red Cross Web site.

Medical offers diabetes, heart testing

Cardiovascular and diabetes screening will be available at Argonne-East Tuesday, Sept. 23, in Building 202, Conference Room B169.

The screening is open to Argonne, Department of Energy and University of Chicago employees, family and retirees. The screening includes a complete blood and lipid profile, body mass index and waist measurement. Individual results will be returned to the physician of the participants.

The screening costs $30; make checks payable to Preventures. Register by Friday, Sept. 19. For more information, contact the Medical Department at ext. 2-2800.

Seminars

Seminars on cardiovascular and diabetes health will take place in the Building 200 Auditorium during October. Seminars begin at 12:15 p.m.

“Results Seminar” by David Ronin. Tuesday, Oct. 14.

“Exercise Your Heart” by Meredith Conn. Thursday, Oct. 16.

“Low-Fat, Low-Sugar, High-Fiber Nutrition” by Meredith Conn. Friday, Oct. 17.

Oktoberfest, Halloween parties are planned

The Argonne Club will host two parties this fall:

The annual Oktoberfest party will be Thursday, Sept. 25, from 4:30 - 8 p.m at 617 Lower Level. Food and adult beverages will be available for purchase.

A Halloween Party will take place Thursday, Oct. 30, from 4 - 8 p.m. at 617 Lower Level. There will be a $3 cover charge, door prizes and a prize for the best costume. Adult beverages will be available for purchase.

All employees, friends and families are invited to these parties. Visitors must be badged by 4 p.m. For more information, visit the Argonne Club Web site or e-mail argonneclub@anl.gov.

Guest House to close on two days

The Argonne Guest House restaurant will be closed during lunch hours Tuesday, Sept. 16, and Wednesday, Sept. 17.

Employees invited to display classic cars

A display of antique and classic cars owned by Argonne-East employees will be held in the Building 360 parking lot Thursday, Sept. 25, at lunchtime.

Owners of cars 25 years old and older, of special interest, modified or of limited production, are invited to show off their vehicles. All employees are invited to stop by, view the cars, take pictures and ask questions.

In case of rain, the car show will be held Thursday, Oct. 2.

For more information, contact Clarence Clark (AOD) at (630) 553-9567 or Walter Czyz (IPNS) at (630) 553-6987.

Rep to assist with Social Security

A Social Security representative will be available in Argonne-East’s Human Resources office from 8 a.m. to noon Wednesday, Sept. 17.

The representative can:

Conduct Social Security enrollment

Take applications for new Social Security cards, including original cards for newborns, corrected cards due to marriage or replacement cards

Help with earnings posting problems

Answer general questions about Social Security.

To schedule a meeting, call Fran Perri (HR) at ext. 2-2989.

MetLife rep will visit ANL-East

A representative from MetLife Auto & Home will visit Argonne-East Tuesday, Sept. 23, to meet with individual employees for insurance comparisons and quotes for the “METPAY” group automobile and homeowners insurance program.

To schedule an appointment, call Craig Riddick at (630) 810-0346, ext. 143. Employees can also receive a quote over the phone by calling 1-800-438-6388.

A MetLife representative will be available Tuesday, Sept. 16, in the Building 213 Cafeteria from 11 a.m. to 1:30 p.m. with promotional material on automobile and homeowners insurance.

SERVICE AWARDS

Service Awards for September include:

40 Years

Gary Leaf (MCS).

35 Years

William E. Chyna (PHY), Terran J. Lucitt (NE).

25 Years

Russell E. Cook (MSD), James P. Derry (PFS), H. Leona Harris (MSD), Lawrence E. Price (HEP), Wayne W. Stevens (FAC), Kim D. Tomasko (ES), Cynthia L. Wilkinson (OPA).

20 Years

Steven J. Bradley (FAC), Stephen Ung-So Choi (ET), Dennis W. Dees (CMT), Therese M. Huml (OTT), Kathleen O’Hare (AIP), Jonathan L. Thron (HEP), Evelyn Wilder (PFS), Cosmas K. Zachos (HEP).

15 Years

Gordon R. Bernard (NT), Amy B. Hull (ET), Walter L. Kazich (PFS), Ronald G. Kolzow (EQO), Sharon Lee Salman (NE), James G. Sleeth (PFS).

10 Years

William R. Brzowski (IPNS), Peter L. Fuesz (AOD), Ira Goldberg (CIS), Rodney E. Habbe (PFS), Thomas G. Quick (PFS).

5 Years

Carmen E. Berry (PFS), Michelle Kehrer (DIS), Arthur Jeremy Kropf (CMT), Rodney R. Porter (IPNS), Kathleen Webb (ER), Jeffrey P. Werner (PFS).