The Scientist 16[9]: 32, Apr. 29, 2002

Carbohydrate Research Headlines
The Scientist

The Scientist 16[9]:32, Apr. 29, 2002
http://www.the-scientist.com/yr2002/apr/profile1_020429.html
There's more to life than DNA, RNA, and proteins. Literally. Sugars are also in the mix. And the roles that carbohydrates play in biology are just as important as those of any member of the better-characterized trinity. These macromolecules affect cell-cell interactions, immune function, and protein regulation, and disruption of their biology results in disease.

One magazine likened the study of carbohydrates, called glycobiology, to Cinderella—neglected stepsister to her two more glamorous siblings, DNA and protein.¹ Momentum is building, however, to do for carbohydrates what scientists have done for genomes, and are attempting to do for proteomes: to characterize the entire complement of these sugar chains in a cell, called the "glycome." Researchers are guardedly optimistic. According to Ajit Varki, professor of medicine and cell and molecular biology, and director of the Glycobiology Research and Training Center at the University of California, San Diego, "we don't know what's going to happen to Cinderella at midnight."

Rockefeller University

Thursday, March 8, 2002
http://www.rockefeller.edu/pubinfo/senalee030802.nr.php
"Sugar-Coating" on Proteins May Safeguard Body against Further Insult
M.D.-Ph.D. student shows mannose receptor performs clearance role

Much like a cadre of emergency workers at the scene of an accident, the body's immune system cells gather at the site of an injury, whether it is a simple cut or an infection. This microscopic crowd largely consists of inflammatory cells and proteins, and together they marshal the immune system's arsenal to bring the offending stimulus under control.

And as so often occurs at the scene of an accident, the crowd lingers. Initially helpful, its presence can create new problems. At the scene of a car accident, the problem may be spectators blocking the travel of the ambulance. In the body, the crowd of inflammatory proteins and other cells can continue to attract more immune system agents than needed. To prevent such an uncontrolled response, a clean-up mechanism is needed to signal the end of the rescue operation.

Now, for the first time, Rockefeller researchers have found that a receptor protein called the mannose receptor on liver endothelial cells performs such a function, which may be important in preventing further damage to healthy tissues.

Inflammatory proteins are initially helpful in repairing an injury inside the body, but are no longer needed when the crisis has passed. Their presence after an injury can harm surrounding tissues. To dispose of them, mannose receptors (violet) are turned on to bind with the complex sugars (yellow) tagging the proteins. The anchoring endothelial cell then engulfs the bound proteins.

Günter Blobel, M.D., Ph.D.
Investigator, Rockefeller University

Winner of the 1999 Nobel Prize for Physiology or Medicine "for the discovery that (glyco) proteins have intrinsic signals that govern their transport and localization in the cell."

Note: 4 out of the last 8... Including the last 3 in a row Nobel Prizes for Medicine have dealt with the cellular communication process and its importance to our wellness (1994, 1999, 2000, and 2001).

Summary

A large number of proteins carrying out essential functions are constantly being made within our cells. These proteins have to be transported either out of the cell, or to the different compartments - the organelles - within the cell. How are newly made proteins transported across the membrane surrounding the organelles, and how are they directed to their correct location?
These questions have been answered through the work of this year’s Nobel Laureate in Physiology or Medicine, Dr Günter Blobel, a cell and molecular biologist at the Rockefeller University in New York. Already at the beginning of the 1970s he discovered that newly synthesized proteins have an intrinsic signal that is essential for governing them to and across the membrane of the endoplasmic reticulum, one of the cell’s organelles. During the next twenty years Blobel characterized in detail the molecular mechanisms underlying these processes. He also showed that similar "address tags", or "zip codes", direct proteins to other intracellular organelles.
The principles discovered and described by Günter Blobel turned out to be universal, operating similarly in yeast, plant, and animal cells. A number of human hereditary diseases are caused by errors in these signals and transport mechanisms. Blobel’s research has also contributed to the development of a more effective use of cells as "protein factories" for the production of important drugs.

MIT News

AUGUST 7, 2002
http://web.mit.edu/newsoffice/nr/2002/sugar2.html
Researchers crack the code of the complex sugar molecule
CAMBRIDGE, Mass.—MIT researchers report in a recent issue of the Journal of the American Chemical Society that their new analytical method unravels the structure of heparan sulfate, a sugar molecule on the surface of all cells in the body, and heparin, a commercial drug used to prevent clotting.
Researchers have been able to determine the structure of proteins and DNA quickly and cheaply for decades. But it has been very difficult to do the same for sugars (polysaccharides), because these molecules are so much more complex and structurally variable.
Heparan sulfate is particularly interesting to researchers because it is involved in normal physiological functions such as tissue regeneration, and also disease-related functions such as developmental disorders and tumor growth.
McGill University

November 5, 2001
Glycobiology: health, disease, and therapy

A scientist from Oxford University whose groundbreaking research may hold the key to future treatments for neurodegenerative disorders like Alzheimer. Says Professor Dwek, "Glycobiology [a word coined by him in 1988 which entered the Oxford English Dictionary in 1992] is the new science concerned with sugars attached to proteins and lipids. Sugars represent the third ’alphabet’ of biology -- the other two being the DNA alphabet and the protein alphabet." His lecture at McGill on November 8 will cover several related topics, including novel approaches to Hepatitis B and Hepatitis C (diseases which chronically infect over 500 million people worldwide), and genetic disorders such as Gaucher’s disease and Tay-Sachs disease. He will also touch on the new proteomics technology, a subject of particular interest to McGill scientists like John Bergeron and genetics expert Tom Hudson.

Dr Maureen Taylor Ph.D.
University of London
The mannose receptor found on macrophages and liver endothelial cells, has a well-documented role in the innate immune response and may also contribute to the acquired immune response. The receptor recognizes pathogens by binding sugars such as mannose and N-acetylglucosamine that are common on the surfaces of micro-organisms but not usually found in terminal positions on mammalian oligosaccharides. The mannose receptor may lie at the nexus of the innate and adaptive immune systems.