Overall Goal and Specific Objectives

To accomplish this goal, the Consortium will:

• Provide an infrastructure to oversee the program


• Approve the selection of representative glycan-binding proteins (GBPs) and glycosyltransferases for study on an ongoing basis


• Ensure that program resources are efficiently used to achieve the program goal


• Generate the resources and services required to achieve the Specific Aims for each GBP selected for study


• Establish a consortium of Participating Investigators to utilize the resources and information generated by the Scientific Cores


• Develop and maintain glycomics databases of human and murine GBPs, glycosyltransferases, and mammalian carbohydrate structures


• Develop and maintain a relational database of all program information with internet-based interfaces for dissemination of all program-derived data

Scientific Rationale and Specific Aims

Based on the few well-documented examples of glycan-binding proteins (GBPs) that mediate cell communication through interaction with their carbohydrate ligands, it is anticipated that many novel paradigms will be discovered among the more than 50 GBPs identified to date. Representative GBPs from four major classes are the focus of the Consortium and are from time to time designated to be priorities by the Steering Committee. Resources generated by the Consortium are anticipated to have broad utility and will be provided to all investigators requesting their use to further Consortium goals. For each GBP the following Specific Aims will be addressed:

1. Define the specificity and affinity for natural and synthetic carbohydrate ligands
2. Establish the cell types involved in communication
3. Identify the ligand(s) on biologically relevant cell types and determine the carbohydrate structure(s) that mediate GBP binding
4. Determine how GBP-ligand interactions mediate cell communication
5. Determine the structures of selected GBPs
6. Identify the glycosyltransferases (or degradative enzymes) responsible for the expression of carbohydrate ligand(s)
7. Determine the extent to which regulation of glycosylation modulates the expression of GBP ligands and controls GBP function

Organization

Three major components comprise the Consortium for Functional Glycomics: the Steering Committee, the Cores (an Administrative Core and seven Scientific Cores), and the Participating Investigators. The Steering Committee consists of 11 members that meet every other week. It has overall responsibility for setting the scientific direction and the budget of the Consortium, and ensuring that information and materials generated by the program are efficiently disseminated within the program and to the public.

Six of the seven Scientific Cores (Cores C-H; see list below) generate material resources, new technologies, and a platform of information that enable progress toward the overall goals. The Information and Bioinformatics Core (B) is responsible for the creation of databases that serve as a window to all program information, and specialized tools that facilitate a glycomics approach to the goals of the Consortium.

• Information and Bioinformatics Core (B)


• Analytical Core (C)


• Carbohydrate Synthesis/Protein Expression Core (D)


• Gene Microarray Core (E)


• Mouse Transgenics Core (F)


• Mouse Phenotype Core (G)


• Protein-Carbohydrate Interaction Core (H)

List of Targets

The Consortium will maintain three major lists of 'targets': glycan-binding proteins (GBPs), the carbohydrate structures they recognize, and the glycosyltransferases (GTs) responsible for the synthesis of the carbohydrates. Each set will be contained in a separate database accessed through the Central Database; these databases are currently under construction.

Selected GBPs that are the focus of the Consortium are provided in a table. A more complete list can be found in the glycan-binding protein database (GBP DB), a site developed and maintained by one of the Steering Committee members, Kurt Drickamer. Fifteen hundred carbohydrate structures have been obtained from Glycominds and are being incorporated into the carbohydrate structure database (Carb DB), which will be updated as new structures become available from the Analytical Core (C) and Participating Investigators. The glycosyltransferase database currently links to the CAZY database developed and maintained by Bernard Henrissat.

In addition, the list of genes represented on the glyco-gene chip can be accessed. All known human and murine GBP and GT genes (see complete gene list) are represented on the glyco-gene chip, which is ready for use by Participating Investigators.

Program Strategy

Each major component of the Consortium interacts directly with the other two. The Steering Committee approves priorities and milestones for each of the Scientific Cores. Setting yearly milestones involves substantial input from the Cores and Participating Investigators. Resources produced by the Scientific Cores are made available to Particpating Investigators for use in performing experiments that address Specific Aims for one or more GBPs. Resource requests are made on-line directly to the Steering Committee. The Scientific Cores are strengthened by their interaction with Participating Investigators who provide expertise and technology.

Public Dissemination of Plans and Results

The public dissemination of plans and results is accomplished in three ways. The first is through the Consortium website. The site currently provides a wealth of general information about the purpose of the Consortium and its policies for dissemination of information and resources. From this site, investigators can join the Consortium and access resources, progress, and future plans.

The second is the Central Database, which will ultimately be the most important mode of accessing detailed program information through user-friendly interfaces. It is currently a beta site that is primarily set up to let the user see some of the features that will be available when the database is ready.

The third is the annual Participating Investigators meeting. It is held in conjunction with the Annual Meeting of the Society for Glycobiology. A full-day general meeting for Consortium Participating Investigators, also open to members of the scientific community who wish to attend, is held following the Society for Glycobiology Meeting.