In our bodies, cells "talk" to each other constantly. Often, this cellular conversation hinges on carbohydrates--sugar molecules that blanket every cell in our bodies. Carbohydrates and proteins associated with them permit cells to transmit and receive chemical, electrical, and mechanical messages that underlie everything from growth to movement to thought.
Yet for the most part, researchers know very little about exactly how our cells use sugars to communicate.
To begin to untangle huge biomedical problems like teasing apart the roles carbohydrates and proteins play in cellular communication, the National Institute of General Medical Sciences has provided a "glue grant" of $7.4 million (for the first year of funding) to a consortium of basic scientists dedicated to studying carbohydrate function. NIGMS anticipates spending a projected total of $34 million on the project over the course of five years.
"For some research, the intellectual and material resources available to individual laboratories, or even to small groupings of labs, are simply not enough to address complex problems like cell communication. Glue grants provide an opportunity to assemble the people and resources needed," said Dr. Marvin Cassman, director of NIGMS.
The precise interactions between carbohydrates and proteins continue to mystify scientists, mainly because carbohydrates have proven to be extremely difficult to study.
"We know enough to say that some sugars carry zip code-like addresses to help cells know where to go in the body, but what we know is just the tip of the iceberg," said project leader Dr. James Paulson of The Scripps Research Institute in La Jolla, California. "Until now, progress in elucidating the functions of carbohydrates has been extremely slow," he added.
Paulson's "Consortium for Functional Glycomics" project (glycomics.scripps.edu) promises to change that by bringing together a large group of scientists from leading academic medical centers across the country. "Glycomics" is the scientific pursuit of identifying and studying all of the carbohydrate molecules produced by an organism.
For years, the study of carbohydrates has languished. Unlike proteins, which are produced for the most part from a single template--an individual gene--carbohydrates are made by a cascade of chemical reactions inside our bodies. Many of these reactions are extremely hard to replicate in the lab.
"The complex, branched structures of carbohydrates have prevented the development of efficient and routine methods that are key to unraveling the rich information content and biological roles of sugar molecules," Paulson noted.
The Consortium's immediate plans include identifying carbohydrate molecules--and proteins that associate with carbohydrates--that collectively play important roles in cell communication. Another key goal of the group will be to figure out how certain cells control the production of the many varieties of sugars involved in cell communication. Ultimately, Paulson expects, many of the findings will better scientists' understanding of the immune system. Immune cells rely heavily on sugars to travel through the blood to lymph glands and to sites of inflammation, and to prompt normal immune responses to foreign invaders like viruses and bacteria.
The Consortium consists of more than 40 researchers from all walks of scientific life--cell biology, chemistry, biophysics, genomics, bioinformatics and genetics. To form the Consortium membership, Paulson attracted leading carbohydrate researchers, but also many scientists whose primary expertise lies in other areas of biomedical science, making up a true cross-disciplinary collaboration.
A cornerstone to the Consortium, and to the NIGMS glue grant program in general, is free and wide access to research results. The Consortium will support four databases to enhance free data access by the scientific community. According to Paulson, the glue grant will allow the group to create unique research tools, such as the databases shared by Consortium members and other researchers.
"This will dramatically accelerate progress in the study of carbohydrates and cell communication," Paulson said.
One of the databases will house three-dimensional structures of carbohydrates; any scientist will be able to plumb the repository for structures related to his or her own research interests.
NIGMS originally conceived of the large-scale glue grants following consultations with leaders in the scientific community who emphasized the importance of confronting intractable biological problems with the expertise and input of large, multifaceted groups of scientists.
The first glue grant was awarded last year to Dr. Alfred G. Gilman, a pharmacologist at the University of Texas Southwestern Medical Center, who won the Nobel Prize in 1994 for work on signaling molecules called G proteins. To date, four large-scale glue grants have been awarded by NIGMS (for a listing and description of awards, see the NIGMS glue grant Web site at: http://www.nigms.nih.gov/Initiatives/Collaborative/GlueGrants)
Joining forces with Paulson's team at The Scripps Research Institute are consortium members from many institutions around the world, including the Massachusetts Institute of Technology; the University of California, San Diego; the Shemyakin & Ovchinnikov Institute (Moscow, Russia); the University of Oklahoma Health Science Center; the University of Dundee (Dundee, Scotland); the La Jolla Institute for Allergy and Immunology; and the University of Michigan Medical Center. The Consortium also includes participating investigators from a dozen or so other universities worldwide.
Please mention support for this work from the National Institute of General Medical Sciences (NIGMS), a component of the National Institutes of Health that supports basic biomedical research. Please fax clips to (301) 402-0224.
CONTACTS
For comment on the glue grant program, call the NIGMS Office of Communications and Public Liaison at (301) 496-7301 to arrange an interview with NIGMS director Dr. Marvin Cassman.
For comment on the Consortium for Functional Glycomics, call Robin Goldsmith of The Scripps Research Institute Office of Communications at (858) 784-8134 to arrange an interview with consortium leader Dr. James C. Paulson.
NOTE TO EDITORS
More information on the NIGMS glue grant program can be found at http://www.nigms.nih.gov/Initiatives/Collaborative/GlueGrants.
More information on the Consortium for Functional Glycomics can be found at: http://glycomics.scripps.edu
