NIGMS Awards "Glue Grant" to Study Cell Talk

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.

The project leader is James Paulson, Ph.D., The Scripps Research Institute (TSRI) and a member of the UCSD School of Medicine’s Glycobiology Research and Training Center (GRTC).  Ajit Varki, M.D., director of the GRTC, and other GRTC members are project collaborators with nearly 20 percent of the glue-grant funding anticipated to go to UCSD to support core resources for glycan analysis and mouse phenotyping. 

Called the “Consortium for Functional Glycomics,” the project brings together more than 40 researchers from all walks of scientific life--cell biology, chemistry, biophysics, genomics, bioinformatics and genetics.  "Glycomics" is the scientific pursuit of identifying and studying all of the carbohydrate molecules produced by an organism.  And, because the precise interactions between carbohydrates and proteins continue to mystify scientists, the Consortium promises to change that by bringing together a large group of scientists from leading academic medical centers across the country. 

“This is a truly exciting and original effort,” said Varki.  “We look forward to working closely with this world-wide consortium of outstanding scientists.  While the ultimate goal of knowing all the sugar structures and their functions is far away, this is a bold and imaginative step in that direction.”

In addition to Varki, who is a steering committee member and core coordinator, UCSD faculty involved in the grant include Jamey Marth, Ph.D. and Steve Hedrick, Ph.D., steering committee members and core coordinators; Dzung Le, M.D., Ph.D., director, Hematology Core; Nissi Varki, M.D., director, Histology Core; Herman van Halbeek, Ph.D., director, Glycan Analytical Core; Bradley Hayes, Ph.D., associate director, Analytical Core.

“The immune system is not centered in a particular organ, but rather it is dispersed throughout almost every tissue in the body. It functions through cell to cell communication, and many of these cellular interactions appear to be mediated by protein-carbohydrate interactions,” noted Hedrick. “The NIGMS award will bring together glycobiologists and immunologists to discover new paradigms in immune recognition and reactivity.”

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 and the complex, branched structures of carbohydrates make development of efficient and routine methods of study a challenge.

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. 

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.  The glue grant will allow the group to create unique research tools, such as the databases shared by Consortium members and other researchers.  This approach is expected to dramatically accelerate progress in the study of carbohydrates and cell communication.

One of the databases will house detailed structures of many carbohydrates; any scientist will be able to plumb the repository for structures related to his or her own research interests.

The Consortium also includes the Massachusetts Institute of Technology; 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; the University of Michigan Medical Center; and additional participating investigators from a dozen or so other universities worldwide.