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Dec. 13, 1999 -- Some of
this week's stories:
Research sheds light on immune system
Millennium party planned
Seminar promises winning proposals
Physicist's
book highlights women of Manhattan Project
Award
entries still wanted
Deer,
darkness lead to danger |
The first detailed pictures of key immune system cells locked onto fragments of a foreign substance provide new clues about how the immune system identifies enemy threats, and may even lead to a new way of vaccinating people against diseases to which they are genetically susceptible.
The investigation, conducted at Argonne, was conducted with support by the National Institutes of Health by a team of researchers at Dana-Farber Cancer Institute. The team collaborated with two scientists from Harvard Medical School and Argonne's Andrzej Joachimiak and Rongguang Zhang (both BIO). The research was published in the Dec. 3 issue ofScience.
The researchers examined their samples at the Structural Biology Center at Argonne's Advanced Photon Source (APS). There the scientists took advantage of the nation's most brilliant X-rays to conduct X-ray crystallography, a process that allows 3-D imaging of changes in crystals as they occur.
The3-D images show that the cells' docking equipment -- or "receptors" -- bind to the protein fragments in a manner not previously recognized. The receptor binds to a relatively short portion of the fragment -- a process that holds true whether the fragment is from a virus, fungus, bacterium or cancer cell. The finding means that scientists can now focus on precisely that area when studying how the cells recognize harmful intruders and bring about their destruction.
"By understanding this fundamental aspect of the human immune response to foreign proteins, we'll gain insights into disorders such as autoimmune diseases and immunodeficiency conditions. We'll also be a step closer to developing new ways of training the immune response to fight specific disorders, including infectious diseases and cancers," say Dana-Farber's Ellis Reinherz and Jia-huai Wang, the study's chief authors.
The study involves immune cells called CD4 T cells, also known as "helper" T cells, whose job is to detect foreign invaders and organize an immune system attack against them.
CD4 T cells are alerted to the presence of infection by features known as antigens that are carried by invading bacteria and viruses. When a cell becomes infected, it displays these antigens on its surface, as if to proclaim its distress to the immune system. The antigens, which are made of peptides (strings of amino acids), are displayed inside tiny "holders" called major histocompatibility complexes (MHCs).
There are two types of MHCs. Class I MHCs hold relatively short peptides that are "read" by CD8 T cells, better known as "killer" T cells. When the peptides inside an MHC class I indicate a cell contains a dangerous virus or bacteria or is in danger of becoming cancerous, the cell will be killed by a CD8 cell.
Class II MHCs hold much longer strings of peptides, which are read by CD4 T cells. When the CD4 cells find foreign or ominous-looking peptides, they trigger an immune response by secreting inflammatory messengers and recruiting additional types of cells, including CD8 T cells, which destroy the infected cell.
The Dana-Farber team has obtained the first close-up, 3-D images of the coupling between the CD4 T cell receptor (or TCR) and peptides ensconced in a Class II MHC. The pictures suggest that no matter what peptide is involved, the TCR will always bind to it on the MHC holder with the same orientation.
The images indicate that the CD4 TCR always docks on top of and at right angles to peptides, much as construction cranes may be lowered perpendicularly to grasp an iron beam. No matter how long the peptide is, the TCR on CD4 cells always covers the same small portion, involving just eight or nine amino acids. Of those amino acids, five or six help anchor the peptide to the MHC, leaving only three or four that are actually in contact with the TCR.
The discovery provides immunologists with a precise target with which to focus their studies of CD4 T cells and their interactions with the body's other cells, the investigators say.
The implications of the research extend far beyond their utility to researchers. Many human diseases, from infectious diseases like AIDS and hepatitis to genetic diseases like cancer, involve, to some degree, problems with CD4 T cells. When CD4 cells are overaggressive and attack healthy cells along with diseased cells, the result can be autoimmune diseases such as diabetes mellitus, multiple sclerosis, and rheumatoid arthritis.
When CD4 cells fail to sound an alarm about diseased cells, the result is immune deficiency that can leave people vulnerable to infections and cancer. Knowing the precise mechanism by which CD4 cells link up with antigens, and how that mechanism can go awry, can provide new insights into the understanding of these and other diseases.
Beyond that, the study points the way to a new form of vaccination -- called thymic vaccination -- that "trains" CD4 T cells to be on the lookout for diseases to which individuals are genetically susceptible.
T cells are produced in the thymus gland (hence the "T") during the first year of life. During that time, they're "educated" to distinguish between the antigens of normal cells (so-called self antigens) -- which are to be left unharmed -- and those of unwanted intruders (so-called foreign antigens) which are to be destroyed.
If a genetic screening of a newborn determined that the infant were at risk for a certain disease -- say breast or prostate cancer as an adult -- doctors could potentially alter the child's repertoire of T cells to increase those that are capable of recognizing and killing such tumors before clinical disease develops, researchers say.
The new study gives impetus to the development of such techniques because scientists now know precisely which form of the peptide would need to be altered to create such a variant: the relatively small section that is the target of the TCR.
Dana-Farber Cancer Institute is a principal teaching affiliate of Harvard Medical School and is one of 35 federally designated Comprehensive Cancer Centers and one of 12 designated AIDS research centers in the United States.
The last cafeteria party of the millennium will be held Thursday, Dec. 16, from 4:30 p.m. to 8 p.m. in Argonne-East's Building 213 Cafeteria.
Music will be provided by a DJ, and adult beverages and food will be available for purchase. Admission will cost $2.
The party is sponsored by Sodexho Marriott.
"Writing Research and Development Proposals," a two-day seminar to be held Jan. 18-19 at Argonne-East, promises to help participants generate "winning" proposals and give sponsors a compelling reason to fund their projects -- without sacrificing the content's technical or scientific integrity.
The course's systematic approach helps participants set themselves apart from other organizations competing for the same funds. The flexible approach can be used for all types of proposals, from "white papers" through formal proposals.
Designed by Lore International Institute for the research and scientific community, and sponsored by Human Resources, the seminar (HR223) will be held from 8:30 a.m. until 5 p.m. each day. The cost is $675. Participants can register through their Training Management System representative. For more information, call ext. 2-3410.
A past participant said the seminar "helped me think about proposal writing as a more scientific, analytical task. I can even apply the techniques to writing other technical articles." Others said the course "gives a fresh new perspective of writing winning R&D proposals with a series of carefully developed tools and logic" and helps reduce "the stress level of proposal writing."
A new book written by Argonne physicist Caroline Herzenberg (DIS) and Ball State University physics professor Ruth Howes chronicles the unsung contributions of women to one of the most intensive scientific projects in history.
Herzenberg will speak about "Their Day in the Sun: Women of the Manhattan Project" at the First Friday Forum meeting on Friday, Jan. 7. Sponsored by Argonne's Women in Science and Technology program, the presentation is open to all.
"Their Day in the Sun" is the culmination of a 10-year effort. The two colleagues got the idea at a conference they attended titled "Women and the Use of Military Force." It occurred to them that most accounts of the Manhattan Project, a top-secret mission to develop the first nuclear weapon, failed to mention any women scientists or engineers involved in the project.
"We tried to uncover the events and untangle the strands of a half-century-old secret project in an effort to bring to light scientific and cultural information that has been largely lost to history," Herzenberg said.
The writers gathered information from interviews, written records, photographs and the Internet, and were able to identify several hundred women physicists, chemists, mathematicians, biologists, technicians and other women who worked on the Manhattan Project.
"At least 85 women helped design and construct the atomic bomb," Herzenberg said. "But you can read through authoritative accounts of the program and never see a word about a woman."
Most of the material was obtained by going through the "old girl network," and telephone interviews. Herzenberg contacted more than two dozen former and current Argonne employees who were either involved in the project themselves or had friends or relatives involved.
Herzenberg said many women scientists in the 1940s were married to scientists and worked for them in their labs for free, devoid of any recognition.
Some of the women profiled in the book include:
Maria
Goeppert Mayer, a Ph.D. physicist whose
previous faculty appointments had been unpaid.
Hired part-time by Columbia University in 1942 to
work on the Manhattan Project, she quickly began
leading 20 scientists and technicians in physics
research. She subsequently worked at Argonne and
received the Nobel Prize for physics in 1963.
Leona Woods, a graduate of the University of
Chicago, developed and operated electronic
equipment and radiation counters. She called out
the neutron counts at the first self-sustaining
nuclear chain reaction on Dec. 2, 1942, and
monitored neutron fluxes in the atomic "piles"
at the University of Chicago and Argonne's Site A.
Elizabeth "Diz" Riddle Graves worked at
Los Alamos developing a neutron reflector to
surround the core of the atomic bomb. She worked
while pregnant and finished a series of
experiments as she went into labor. She and her
husband monitored radioactive fallout from the
first nuclear explosion, the Trinity Test in New
Mexico.
This is Herzenberg's second book. Her first book, published in 1986, lists some 2,500 women from the fields of medicine, science, engineering and technology.
The book can be ordered at major book stores or through Temple University Press.
-- Linda Jakubowski
There is still time to submit entries for the 2000 Discover and R&D 100 technology awards.
Industrial Technology Development (ITD) is assisting Argonne researchers with their award entries. First drafts for Discover Award entries will be accepted before the holiday break, and R&D 100 Award entries after the break.
Details on entry format are available online.
To submit an entry, contact Shari Zussman at ext. 2-5936 or send e-mail to zussman@anl.gov.
The combination of deer mating season and earlier darkness has led to several close calls for drivers on Argonne-East's Westgate and Northgate roads.
The best way to avoid several hundred dollars' worth of damage to one's car -- and possible serious injury -- is to obey the posted speed limits on these roads and scan the treelines on either side, said Ed Mickulas, security administration manager. So far this year, only one deer-car collision has been reported. Three collisions were reported in 1988.
Argonne Club is looking for three new officers for its board of directors.
Officers serve three-year terms and help plan the Argonne Club's activities, like Breakfast with Santa, the Argonne-East employee picnic and group outings.
For more information, call Dan McNamee (PFS) at ext. 2-6539.
