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CFG PI 2006

Consortium for Functional Glycomics

Participating Investigator Meeting

Universal City, CA

November 19, 2006

Biology of glycan binding proteins:

Insights from glycan microarrays

(CFG: Another 5 years!)

CFG PI 2006

Consortium for Functional Glycomics

Goal:

Define paradigms by which protein-

carbohydrate interactions mediate cell

communication

http://www.functionalglycomics.org

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

The next 5 years

Funding of $41.8 million by NIGMS.

Priority is to achieve the overarching goal to

unfold the biology of glycan binding proteins,

`define the paradigms' using resources created

in first 5 years.

Enhance utility and availability of existing

resources and databases

Evergreen the unique resources and databases

to insure availability to the community at the end

of the 10 year project.

CFG PI 2006

Soluble GBPs binding cell surface and

pathogen glycans

Glycoprotein

lattice

Opsonization

Glycan specific

antibody

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Cell surface GBPs binding pathogen

and glycoprotein glycans

Microbe

Recognition

Glycoprotein

Targeting

CFG PI 2006

Cell surface GBPs binding cell surface

glycans

Trans ligand:

Cell adhesion

Cis ligand:

Receptor signaling

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Attachment of microbial pathogens to

host cell glycans

Virus attachment

and endocytosis

Bacterial

colonization

Toxin

attachment

CFG PI 2006

Information needed to elucidate GBP function

Specificity of GBP for its glycan ligands

Cell type expression of GBPs and its
ligands

Glycan structures expressed on cell
types/glycoproteins recognized by GBP

Glycosyltransferases responsible for
synthesis and regulated expression of
GBP ligands

Structures of GBPs

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

Part. Investigators

·Explore Biology

using tools

·Contribute data

> 180 Institutions

Consortium for Functional Glycomics

Glycan Library

Tools for specificity

analysis and biology

TSRI

Mouse Phenotype

UC San Diego

Mouse Transgenics

Create & Distribute

KO mice

TSRI

Consortium Databases

MIT

Steering Committee

Analytical

Glycan Profiling

Imperial

College

Glycan Microarray

GBP ligand specificity

Emory Univ.

Gene Microarray

GBP and GT gene

expression

TSRI

Part. Investigators

·Explore Biology

using tools

·Contribute data

> 180 Institutions

Part. Investigators

·Explore Biology

using tools

·Contribute data

> 180 Institutions

Part. Investigators

·Explore Biology

using tools

·Contribute data

> I80 Institutions

CFG PI 2006

Consortium for Functional Glycomics :

Glycobiology resources offered

Analyze your mRNA
on a custom gene
microarray
including 2,000
human and mouse
glyco genes

Glyco-gene microarray

Over 230
carbohydrate
compounds
available with
azido or biotin
functional
groups

Carbohydrate compounds

Novel knockout
mouse strains
with genes
ablated for glycan-
binding proteins

Mouse knockout strains

Profile and
characterize the
N- and O-linked
glycans from
your tissues and
cell lines

Glycan Analysis

Phenotype charac-
terization of mice in
the public domain
with deleted glycan-
binding protein
genes

Mouse Phenotype Analysis

Determine the
specificity of your
glycan-binding protein
on a microarray with
~300 glycoprotein and
glycolipid glycans

Glycan array screening

www.functionalglycomics.org

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Accelerating rate of resource requests

Year 5

Year 1 Year 2

Year 3

Year 4

CFG PI 2006

Analytical Glycomics Core

Focused glycan MS profiling

of purified human and murine

cell populations and

glycoprotein ligands of GBPs.

Coordinate glycan profiling

and GT gene expression

datasets with Gene Microarray

Core (E).

Goal to increase throughput

with automated annotation

and improved micro-sample

handling.

Goal to integrate data with

other database and

informatics features.

Analytical Core

Stuart Haslam, Simon

North, Anne Dell

Imperial College

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Glyco-gene Microarray Core

GLYCO-gene chip v3 with human and
murine GBP and GT families represented
(>200 GT genes).

Highly annotated by experts in each gene
family

`Popular' resource by investigators

Strategic goal to match gene expression of
human and murine cell populations with
glycan profiling by Core C.

Data accessible with data mining tools
posted on the CFG website.

Regularly update technology and chip
design

Interogate data from database interfaces.

Glyco-gene Microarray Core

Steven Head

Tim Gilmartin

The Scripps Research Institute

CFG PI 2006

Mouse Transgenics / Phenotyping

Major success in germline

transmission from C57Bl/6 ES

cells.

Six novel KO strains available

and 18 additional in

development.

Additional ~50 `published' KO

strains available from Jackson

Laboratories, MMRC and

Participating investigators.

Phenotype data deposited into

the CFG database.

Develop mentor program for

generation and phenotyping of

KO mice.

Mouse Transgenics Core

Bo Ma

James Paulson

TSRI

Mouse Phenotyping Core

Sally Orr

Jamey Marth

UCSD

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Glycan micro-array for GBP specificity

Glycan library with ~230

synthetic glycans and

glycan derivatives

available on request.

Printed glycan array with

~300 synthetic glycans

represented.

Expand Reagent Library to

include glycan specific

antibodies and

glycosyltransferases.

Expand uses of existing

glycan microarray

Develop a pathogen glycan

microarray.

Glycan-Protein

Interaction Core

David Smith

Richard Cummings

Emory University

Glycan Microarray

Synthesis Core

Ola Blixt,

James Paulson /

Chi-Huey Wong

TSRI

CFG PI 2006

Initiatives emerging from glycan array

Centers for Disease Control

agreement with

CFG to make custom glycan microarray for
evaluation of its utility for screening
specificity of influenza virus field isolates

National Cancer Institute

Early Diagnosis

Research Network (RFA) for glycomics
biomarkers with CFG as partner, targeting
~$3 million per year in grants.

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Bioinformatics

Implement vision for CFG

databases developed with

the SC, Scientific Cores

and Participating

Investigators.

Develop interfaces for

acquisition and

dissemination of

Consortium data.

Develop specialty

databases integrated with

CFG data as resources

for PIs and the scientific

community.

Bioinformatics

Rahul Raman

Ram Sasisekharan

MIT

CFG PI 2006

Integration of interfaces for CFG data and

specialty databases

Glycan-

Transferase DB

Biosynthesis

Glycan

Structures DB

Structure

Glycan Binding

Protein DB

Biology

Glycan

array data

Glycogene

microarray

data

Analytical

glycomics

data

Mouse

Phenotype

data

Consortium Data

Specialty Databases

Implemented
Planned

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Integration of interfaces for CFG data and

specialty databases

Glycan

Structures DB

Structure

Glycan Binding

Protein DB

Biology

Glycan

array data

Consortium Data

Specialty Databases

Implemented
Planned

CFG PI 2006

Integration of interfaces for CFG data and

specialty databases

Glycan-

Transferase DB

Biosynthesis

Glycan

Structures DB

Structure

Glycan Binding

Protein DB

Biology

Glycan

array data

Consortium Data

Specialty Databases

Implemented
Planned

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Forge Alliances with Other Consortia and

Database Organizations

Identify synergies with

existing consortia and

databases.

Leverage resources to

mutual benefit.

Develop uniform

standards for depositing

and sharing data

Facilitate ever-greening

resources and

databases

Steering

Committee

Participating

Investigators

Scientific

Cores

Other

Consortia

CFG PI 2006

Glycan structure database

Data exchange with other initiatives

Glycan DB

XML format -

Exchanging

Information

NIH Workshop on Glycomics Bioinformatics and

Biomarkers in Disease September 11-13, 2006

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Leverage resources through alliances

CAZy: Carbohydrate Active-EnZYmes (Bernard Henrissat)

CCRC/NCRR : Integrated Technology Resource for Biomedical

Glycomics (Michael Pierce)

Correlation of microarray/RT-PCR methods for GT expression

Link Glycan Database to 3D-Glycan Structure Resource (Rob Woods

Database XML standards (Will York)

EuroCarbDB : - (Willi von der Lieth)

Coordination of carbohydrate databases and data exchange standards

KEGG glycan project (Minoru Kanehisa)

Annotation of GT database; analysis of microarray data

HGPI: HUPO glycomics disease initiative (Naoyuki Taniguchi

)

Japanese Consortium for Glycobiology and Glycotechnology (JCGG)

(Yoshi Nagai / Hisashi Narimatsu)

Joint Center for Structural Genomics (Ian Wilson)

Crystal Structures of Glycan Binding Proteins and GTs

Lipid MAPS Consortium (Ed Dennis/Al Merrill)

Annotation of glycolipid biosynthetic pathways

UK Glycochip Consortium (Sabine Flitch)

Coordinate efforts on design of glycan microarrays

GLYCOARRAYS STRATEGIES FOR HIGH

THROUGHPUT ANALYSIS OF THE GLYCOME

http://www.glycochips.org.uk/

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

8:55 9:20

Dave Smith

(Emory University)

CFG Glycan array analysis

9:20 9:45

Kurt Drickamer

(Imperial College of London)

Glycan array analysis of receptors that bind

endogenous and pathogen glycans

9:45 10:10

Mavis Agbandje-McKenna

(University of Florida)

Glycan array and structural analyses of

parvoviral-host cell receptor interactions

10:10 10:35

Els van Damme

(Ghent University)

Diverse specificities of plant lectins

revealed on glycan microarrays

10:35 11:05

MORNING BREAK

Biology of glycan binding proteins:

Insights from glycan microarrays

CFG PI 2006

11:05 11:30

David Miller

(University of Illinois at Urbana-Champaign)

Glycomic approach to identify oligosaccharides

that bind sperm

11:30 11:55

Ola Blixt

(The Scripps Research Institute)

Developments in CFG glycan and pathogen

polysaccharide arrays

11:55 1:00

LUNCH

1:00 1:30

Rahul Raman

(Massachusetts Institute of Technology)

Enhancements to CFG databases and interfaces

1:30 2:30

Investigator Feedback on CFG Initiatives

Co-Chairs: Rick Cummings & Steve Rosen

Biology of glycan binding proteins:

Insights from glycan microarrays

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007

CFG PI 2006

Acknowledgments

Advisory Committee

Elizabeth Neufeld

Ellis Reinherz

Nathan Sharon

Steering Committee

Paul Crocker

Richard Cummings

Anne Dell

Kurt Drickamer

Pamela Marino

Jamey Marth

James Paulson

Steve Rosen

Ram Sasisekharan

Ron Schnaar

Pamela Stanley

Scientific Cores

Ola Blixt

Steve Head

Stuart Haslam

Bo Ma

Sally Orr

Rahul Raman

David Smith

Participating

Investigators

~300

Sponsors:

NIGMS

Neose Technologies

Kyowa Hakko

Otsuka Phamaceuticals

NRC Ottawa

CFG PI 2006

Nature Precedings : doi:10.1038/npre.2007.11.1 : Posted 15 Jan 2007