Consortium for Functional Glycomics

Consortium for Functional Glycomics

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The Consortium for Functional Glycomics
Glycomics
Glycomics is the comprehensive study of glycomes , including genetic, physiologic, pathologic, and other aspects. Glycomics "is the systematic study of all glycan structures of a given cell type or organism" and is a subset of glycobiology...

(CFG) is a large research initiative funded in 2001 by a glue grant from the National Institute of General Medical Sciences
National Institute of General Medical Sciences
The National Institute of General Medical Sciences is a part of the National Institutes of Health that primarily supports research that lays the foundation for advances in disease diagnosis, treatment and prevention...

 (NIGMS) to “define paradigms by which protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

-carbohydrate
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...

 interactions mediate cell communication”. To achieve this goal, the CFG studies the functions of:
  • the three major classes of mammalian glycan-binding proteins (GBPs): C-type lectin
    C-type lectin
    A C-type lectin is a type of carbohydrate-binding protein domain known as a lectin. The C-type designation is from their requirement for calcium for binding. Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and...

    , galectin
    Galectin
    In molecular biology, galectins are a family of lectins which bind beta-galactoside. The family is defined by having at least one characteristic carbohydrate recognition domain with an affinity for beta-galactosides and sharing certain sequence elements...

    , and SIGLEC
    SIGLEC
    Siglecs, short for sialic acid binding Ig-like lectins are cell surface receptors and members of the immunoglobulin superfamily that recognize sugars. Their ability to recognize carbohydrates using an immunoglobulin domain places them in the group of I-type lectins...

  • immune receptors that bind carbohydrates: CD1
    CD1
    For the album by Throbbing Gristle, see CD1 CD1 is a family of glycoproteins expressed on the surface of various human antigen-presenting cells. They are related to the class I MHC molecules, and are involved in the presentation of lipid antigens to T cells...

    , T cell receptor
    T cell receptor
    The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...

    , and anti-carbohydrate antibodies
  • GBPs of microorganisms that bind to host cell glycans as receptors.


The CFG comprises eight core facilities and 500+ participating investigators that work together to develop resources and services and make them available to the scientific community free of charge. The data generated by these resources are captured in databases accessible through the Functional Glycomics Gateway, a web resource maintained through a partnership between the CFG and Nature Publishing Group
Nature Publishing Group
Nature Publishing Group is an international publishing company that publishes academic journals, online databases, and services across the life, physical, chemical and applied sciences and clinical medicine...

.

Organization


The CFG is composed of three main components: the Participating Investigators, the Cores, and the Steering Committee.

Participating Investigators


Progress towards the CFG’s overall goal is driven by the research of more than 500 Participating Investigators (PIs) around the world, whose laboratories utilize resources, services, and data produced by the CFG scientific cores.

The PIs are the largest component of the program, continuing to grow with new members each year. Each PI also has a program of research within the scope of the CFG, supported by non-CFG funds. Investigators apply for membership and must have a funded grant within the scope of the CFG, but they are not required to join the CFG to access resources. Several PIs also have CFG-funded bridging grants that are primarily tied to and enable the goals of the scientific cores, for the benefit of all PIs.

The PIs are organized into 10 subgroups led by Subgroup Leaders:
  • Microorganism recognition of host glycans
  • Immune recognition of glycans
  • Glycans in immune cell communication
  • Glycans in development and physiology
  • Glycans in cancer biology
  • Glycans in protein conformation and function
  • Analytical glycomics
  • Chemical synthesis and glycan microarrays
  • 3-D Structural glycobiology
  • Bioinformatics


The subgroups hold at least three workshops per year, where they have formed several working groups to leverage CFG funding in their efforts to define GBP biology. PI contributions toward elucidating paradigms that define GBP function are captured in the CFG’s databases, as well as research publications and review articles.

Cores


The majority of CFG funds are invested in the scientific cores, which are responsible for generating novel resources, new technologies, and a platform of information that investigators use in their research. The eight CFG cores are described below:
  • Administrative Core (A), located at The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , supports the CFG steering committee, cores, and participating investigators, plans meetings and workshops, publishes a quarterly newsletter, facilitates resource requests, tracks CFG-related publications, and writes progress reports to NIGMS. Core A also works closely with Core B to update and develop new content for the Functional Glycomics Gateway site.
  • Bioinformatics Core (B), located at the Massachusetts Institute of Technology
    Massachusetts Institute of Technology
    The Massachusetts Institute of Technology is a private research university located in Cambridge, Massachusetts. MIT has five schools and one college, containing a total of 32 academic departments, with a strong emphasis on scientific and technological education and research.Founded in 1861 in...

    , is responsible for acquiring, storing, and disseminating all CFG-related data and information. For this purpose, Core B works with Nature Publishing Group to develop the CFG’s Functional Glycomics Gateway site. Here, Core B has constructed complex relational databases to integrate diverse data sets generated by the CFG scientific cores and participating investigators, as well as data sets from other public databases. To increase the usability of these databases, Core B collaborates with the scientific cores to develop bioinformatics tools for data mining and prediction
  • Analytical Glycotechnology Core (C), located at Imperial College London
    Imperial College London
    Imperial College London is a public research university located in London, United Kingdom, specialising in science, engineering, business and medicine...

    , offers mass spectrometry
    Mass spectrometry
    Mass spectrometry is an analytical technique that measures the mass-to-charge ratio of charged particles.It is used for determining masses of particles, for determining the elemental composition of a sample or molecule, and for elucidating the chemical structures of molecules, such as peptides and...

     profiling of protein N- and O-linked glycans from mammalian cells, with highest priority given to pure populations of human or murine immune cells.
  • Glycan Array Synthesis Core (D), located at The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , produces and collects carbohydrate compounds (monosaccharides, disaccharides, etc.), glycan-binding proteins, and anti-glycan antibodies for distribution to investigators. Many of these reagents were generously contributed by participating investigators. Core D also synthesizes glycans for and prints the CFG glycan array (see Core H below)
  • Gene Microarray Core (E), located at The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , screens RNA samples provided by investigators on a custom-designed glycogene chip array developed using Affymetrix
    Affymetrix
    Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...

     technology. The chip contains probe sets designed to monitor the expression of approximately 2000 human and mouse genes, including glycosyltransferases, glycan-binding proteins, glycan degradation proteins, intercellular protein transport proteins, sugar transporters, adhesion molecules, interleukins, mucins, growth factors, cytokines, chemokines, and more.
  • Mouse Transgenics Core (F), formerly located at The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

    , is now closed. From 2001-2009, Core F generated 26 total and conditional knockout mouse lines deficient in glycan-binding proteins or glycosyltransferases. All Core F strains are now archived at the Mutant Mouse Regional Resource Center (MMRRC) at the University of California, Davis
    University of California, Davis
    The University of California, Davis is a public teaching and research university established in 1905 and located in Davis, California, USA. Spanning over , the campus is the largest within the University of California system and third largest by enrollment...

     or The Jackson Laboratory (Jax). As a service to the community, the CFG still maintains a site in the Functional Glycomics Gateway to help investigators locate potential sources of glycogene knockout mouse lines: http://www.functionalglycomics.org/static/consortium/resources/resourcecoref.shtml
  • Mouse Phenotype Core (G), located at the Sanford-Burnham Medical Research Institute, works with participating investigator “mentors” to assess the histology, hematology, metabolism, immunological function, and behavior of Core F-generated mouse lines in order to describe the phenotypic results of deleting one or more glycogenes. At the discretion of the Mouse Subcommittee, Core G also occasionally evaluates mouse lines provided by investigators.
  • Protein-Glycan Interaction Core (H), located at Emory University
    Emory University
    Emory University is a private research university in metropolitan Atlanta, located in the Druid Hills section of unincorporated DeKalb County, Georgia, United States. The university was founded as Emory College in 1836 in Oxford, Georgia by a small group of Methodists and was named in honor of...

    , analyzes investigator-generated lectins, antibodies, antisera, microorganisms, or suspected glycan-binding proteins of human, animal, and microbial origins on a mammalian glycan array to determine carbohydrate specificity and identify specific ligands. The current version of the array (v4.1), developed and printed by Core D, contains 465 different glycans.

Steering Committee


The CFG is managed by a steering committee chaired by James Paulson, Ph.D., professor at The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...

and Principal Investigator of the CFG glue grant. Eleven additional glycomics experts and one NIGMS scientific officer make up the rest of the committee.

Five subcommittees oversee the cores and make recommendations to the steering committee regarding resource priorities and technology development: Bioinformatics Subcommittee, Glycan Array/Carbohydrate Library Subcommittee, Glycan Analysis Subcommittee, Mouse Subcommittee, and Nomenclature Subcommittee.

Resources


The CFG resources and services described above are free for the use of investigators studying the complex biology that governs the interactions of glycan-binding proteins and their ligands in mediating cell communication.

Resources can be requested by submitting a form at the Functional Glycomics Gateway website. Once a request is received, the appropriate core director reviews it and contacts the investigator if more information is needed. Once the core director finalizes a request and determines whether or not the core is capable of fulfilling it, the CFG Steering Committee reviews the request for final approval.

Membership in the CFG is not a requirement for receiving resources, but an investigator's institution must endorse the CFG's data sharing agreement in order to complete the resource request process.

Databases


Data obtained by CFG scientific cores with samples submitted by PIs, and data obtained by investigators in their own labs using CFG resources, are uploaded into the CFG databases for dissemination to investigators and to the scientific community. Specialty databases for GBPs, glycan structures, and glycosyltransferases are designed to help integrate data and assess progress against the overall goal.

The easiest way to search through all CFG-related information is to enter a keyword (e.g. “galectin-1”, “sialic acid”, etc.) or IUPAC carbohydrate nomenclature in the search box at the top of the Functional Glycomics Gateway.

Funding


In 2001, the CFG was awarded a five-year, $34 million glue grant from NIGMS. In 2006, the CFG glue grant was renewed for another five years with an additional $40.7 million. Glue grant funding will end August 31, 2011. The CFG plans to seek alternate funding to continue many aspects of the CFG beyond the glue grant funding period.

External links