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1
Introduction
1.1 UNDERSTANDING THE LANGUAGE OF
LIFE: THE CENTRALITY OF SUGARS
Sugars (see Box 1-1) are everywhere. They are the foundation of all
life on Earth. The most important biochemical process on Earth is pho-
tosynthesis--plants, algae, and other similar organisms using the energy
in sunlight to combine carbon dioxide and water to make sugars. Many
of the resulting sugars in plants end up as either starch or cellulose, both
polymers of the sugar glucose. Such polymerized sugars--called oligosac-
charides, polysaccharides, carbohydrates, or, generically, glycans--are the
most abundant molecules on the planet. Cellulose is a polymer of glucose
that provides the structural support for all plants and trees, as well as
the raw material for clothing, paper products, and wood products. While
humans cannot digest cellulose--it is an important part of the indigest-
ible "fiber" in our diets--grazing animals can, and it serves as their major
source of energy. Starch is another glucose polymer. It differs only subtly
from cellulose, yet humans can digest it into its component glucose mol-
ecules, the central feedstock for our metabolic pathways. Human metabo-
lism, and the metabolism of virtually all living things, harvests energy
by breaking down glucose into water and carbon dioxide, which is then
ready to undergo another round of fixation by photosynthesis.
Glucose is key to life, but it is also central to disease. Diabetes, for
example, results when glucose is not properly controlled by normal meta-
bolic mechanisms. High concentrations of glucose can result in organ
damage, while low concentrations can lead to loss of consciousness and
13
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14 TRANSFORMING GLYCOSCIENCE
BOX 1-1
Carbohydrate, Glycan, Saccharide, or Sugar?
Carbohydrate: A generic term used interchangeably in this report with sugar, sac-
charide, or glycan. This term includes monosaccharides, oligosaccharides, and
polysaccharides as well as derivatives of these compounds.
Glycan: A generic term for any sugar or assembly of sugars, in free form or at-
tached to another molecule.
Saccharide: A generic term for any carbohydrate or assembly of carbohydrates, in
free form or attached to another molecule.
Sugar: A generic term often used to refer to any carbohydrate, but most frequently
to low molecular weight carbohydrates that are sweet in taste.
sudden death due to inadequate energy. Diabetics must measure their
blood sugar frequently to ensure proper glucose levels. Such measure-
ments account for a significant number of the total number of diagnostic
tests conducted each year in developed countries.
But glucose is not the only sugar molecule of importance to human
health. Our cells carry complex sugars that comprise individual sugar
molecules linked to one another in a multitude of ways. These complex
sugars are usually referred to as glycans. Glycans are one of the four major
classes of macromolecules--nucleic acids, proteins, and lipids being the
other three--that are essential for life and are involved in every aspect
of biology, medicine, and a number of practical applications. These other
three classes often incorporate or rely on glycans for their activity--
nucleic acids contain the carbohydrates ribose or deoxyribose, whereas
proteins and lipids often require appended glycans for activity (glycopro-
teins and glycolipids, respectively). These structures, and combinations
of these structures, contain information that is used for a wide variety of
biological processes. Key facts about glycans and glycoscience are given
in Box 1-2.
For example, one result of 3 billion years of evolution is that every
cell of every organism is coated with a layer of glycans--the glycocalyx in
animals or the cell wall in prokaryotes, plants, and fungi (see examples in
Figure 1-1). The glycocalyx/cell wall contains high information content.
On red blood cells the different sugars of the glycocalyx are responsible
for the different blood groups--A, B, AB, and O (see Box 1-3). On cells of
organs, these and other aspects of the glycocalyx can determine whether a
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INTRODUCTION 15
BOX 1-2
Important Facts About Glycans
General
1. Glycans are the most abundant family of organic molecules on the planet.
2. The potential information content of glycans vastly exceeds that of any other
class of macromolecules.
3. Every living cell on the planet is covered with a dense and complex array
of glycans. These glycans form the glycocalyx in many types of cells (such
as in humans) and comprise the cell wall in others (such as plants). Some
cells do not have a nucleus, but all have a glycocalyx or cell wall.
4. Every molecule, cell, or organism that interacts with a cell must do so in the
context of the glycocalyx or cell wall.
5. The vast majority of cellular and secreted proteins are modified with gly-
cans, which modify, alter, and/or control their functions.
Health
1. Elimination of any single major class of glycans from an organism results
in death.
2. Every disease that affects humans significantly involves glycans.
3. A great majority of host-pathogen interactions involve glycans, via recogni-
tion, degradation, or molecular mimicry.
4. Most protein therapeutics must be glycosylated properly to be functionally
effective.
5. Altered glycosylation is a universal feature of cancer and contributes to
pathogenesis and progression.
6. Many vaccines are glycan based.
Sustainability
1. Glycoscience is one of the only fields that directly impacts both the phar-
maceutical and energy industries.
2. The majority of solar energy trapped as cellular energy is converted to
carbohydrates.
3. There are no other candidate classes of molecules that can solve our en-
ergy and materials needs.
4. Petroleum resources have finite lifetimes, but polysaccharide resources are
continually being created with the sun's energy.
5. Nitrogen fixation in plants depends on carbohydrate signaling between
bacteria and plant roots.
particular person in need of a heart, liver, or kidney transplant can receive
an organ from a particular donor.
Indeed, cell surface glycosylation (i.e., the process by which cells cre-
ate and display their glycocalyx) is as important to understanding life as
is the genetic code, yet our understanding of the information contained
in glycosylation is rudimentary at best. In large part this lack of knowl-
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16 TRANSFORMING GLYCOSCIENCE
Figure 1-1 left
FIGURE 1-1 Glycans are significant components on biological surfaces and as
parts of biological molecules. Top, Image of a red blood cell showing the glyco-
calyx extending from the membrane surface. SOURCE: Voet and Voet 2010, used
with permission. Bottom, Scale model of a protein showing the relative sizes of
the N-linked glycans andFigure 1-1 right
GPI-anchors that are attached to it. SOURCE: Varki et
Bitmapped
al. 2009, used with permission.
edge results from two factors: (1) the remarkable structural complexity
of glycans found on cell surfaces and (2) a lack of tools for deciphering
glycosylation patterns. Glycans thus got "left behind" in the initial phase
of the modern revolution in molecular and cellular biology, resulting
in a generation of scientists who may be largely unfamiliar with and
untrained in the study of these key molecules of life.
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INTRODUCTION 17
BOX 1-3
ABO Blood Groups
One of the most familiar ways in which the glycan information of a cell influ-
ences phenotype is the ABO blood grouping, which is a significant factor in deter-
mining which blood transfusions can be carried out. With rare exceptions, human
red blood cells contain on their surfaces a core carbohydrate sequence (called the
"H antigen"). The familiar ABO blood types derive from further modifications to this
H carbohydrate chain. In the genome, the locus that determines ABO type encodes
for a glycosyltransferase. Different variants of this enzyme either are non-functional
and therefore don't alter the H carbohydrate (type O) or add slightly different sugars
to it (type A and type B; see image). Because a person receives DNA from both
parents, the four possible blood types are O, A, B, and AB. Immune antibodies can
form against the types of sugar chains that an individual does not have on his or
her red blood cells. Thus, a person with type O blood may form anti-A and anti-B
antibodies that prevent him or her from successfully receiving blood from anyone
other than a similar type O donor. On the other hand, a person with both type A and
type B carbohydrate chains will not form antibodies against either and can receive
blood from any ABO source. As a caveat, it is important to recognize that the ABO
system is not the only factor that determines transfusion acceptance and thus the
above description is not absolute. For example, humans also have red blood cell
proteins that influence transfusion acceptance (for example, Rh factor). However,
the ABO system helps illustrate how small differences in glycans translate to practi-
cal, physiological differences. The possibility of modifying the surface glycans on
red blood cells to avoid ABO incompatibilities is also being explored (Olsson and
Clausen 2008; Liu et al. 2007).
Representation of ABO sugars on red
blood cells. SOURCE: Varki et al. 2009,
used with permission.
Box 1-3
Bitmapped
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18 TRANSFORMING GLYCOSCIENCE
The complexity and high information content of glycans result from
the many ways in which they can be assembled from simple sugar building
blocks. This is in contrast to the simple ways that building blocks of pro-
teins and nucleic acids--the amino acids and nucleotides, respectively--
are linked together. Protein and nucleic acid biopolymers are linear, and
every building block is linked to the next through the same kind of con-
nection. By contrast, sugar building blocks can be linked together at many
different sites and in different spatial orientations (i.e., stereochemistries),
creating both linear and branched polymers with a wide variety of shapes
(see Figure 1-2). Between the combination of structural diversity and dif-
ferent possible connection sites, the complexity of glycans increases rap-
idly. This diversity not only gives rise to many important and interesting
biological functions and chemical properties but also creates challenges
for synthesis, purification, and characterization--structure elucidation
challenges discussed in detail later in this report.
The tools available today for fully characterizing the complex struc-
tures of glycans at low levels are mostly destructive, making it largely
impossible to follow the changes in glycosylation that occur on a cell's
surface over time. In addition, the diversity of glycan structures makes
full characterization of the cell surface glycome (i.e., the totality of gly-
cans with which a cell is coated) an incredible challenge, one beyond
HO
A B C
H
O N
O
HO
O HO
O
O
O OH OH
HO OH
HO
O O
HO
O
OH
HO HN
OH
HO O
FIGURE 1-2 Comparison of nucleic acids, proteins, and glycans. A, glycan; B,
nucleic acid; C, protein.
Figure 1-2 New 10/3/12
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INTRODUCTION 19
the capabilities of current technology. Today, it is possible to obtain only
a general idea of the composition of the glycocalyx or cell wall, rather
than a detailed molecular-level description. Yet these surface glycans are
essential to both understanding and treating many diseases. The pattern
of sugars on a cell causes pathogens--viruses and bacteria--to attack
certain cell types. Many bacteria and viruses recognize specific sugars on
particular cell types. In turn, a person's immune system generates anti-
bodies to these invaders based largely on the glycans on these pathogens.
Adding complexity, many pathogens carry out molecular mimicry of host
glycans in order to evade immune responses. In addition, there is growing
evidence that the glycans on cancer cells differ from those on normal cells,
presenting a promising opportunity for diagnosis, imaging, and therapy.
In addition to their roles on cell surfaces, glycans play important roles in
biological communication and signaling (see Box 1-4).
In the area of energy, sugars play an increasingly important role as
scientific innovations drive advances in developing energy sources that
will be renewable and contribute less to global climate change. Complex
glycans, such as the starches and cellulose in plant cell walls (referred to
as biomass), are Earth's primary storage location for the products of fixa-
tion of carbon into molecules via photosynthesis. These glycans are being
exploited as renewable sources of liquid biofuels, such as ethanol. As
described above, these materials ultimately can trace their energy content
to the sun, so they can be thought of as a form of solar energy--and just
as renewable. The challenge is to efficiently harvest the energy contained
in the large amount of glycans produced by plants.
Glycoscience is uniquely poised to make significant contributions
to this need. The polysaccharide components of the insoluble cell walls
include cellulose, hemicelluloses, and pectins--polymers of sugars that
are sometimes linear (cellulose) and sometimes branched (hemicelluloses
and pectins). These walls have a generalized global structure, with cellu-
lose embedded in a matrix of other molecules, although the fine details of
wall structure differ across plant species, across different plant tissues and
organs, and indeed across walls in single cells. A major challenge to plant
glycoscientists is to understand how these cell wall components are bio-
synthesized and how they are put together with lignin to form insoluble
plant biomass, as well as how to manipulate and break down biomass
more effectively in order to release the sugars for development into fuels.
Glycans can also be used as important materials--for example, as
gelling agents in foods--and as a renewable resource for high-value
chemicals, plastics, and pharmaceuticals. Wood, comprised of lignocel-
luloses, is a major building material and is used in myriad applications.
Other materials, such as most plastics, are derived primarily from petro-
leum. Glycans can play an important role either as a starting material to
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20 TRANSFORMING GLYCOSCIENCE
BOX 1-4
Glycan Signaling in Nitrogen Fixation
Nitrogen is an essential element in biological systems and is a key component
of proteins and other molecules. To be usable by most organisms, however, the
nitrogen available in the atmosphere must first be fixed or converted into ammo-
nium. Before the development of chemical fertilizers, all nitrogen fixation occurred
biologically through the action of bacteria capable of undertaking these reactions.
Biological nitrogen fixation remains a significant source of bioavailable nitrogen.
Although several types of bacteria can fix nitrogen, one important example is the
symbiotic relationship that exists between species of Rhizobia bacteria and the
roots of legumes. Chemical signals (flavanoids) released by plant roots activate
Nod genes in the bacteria. Turning on these genes leads to the production and
release of a glycoconjugate called Nod factor that binds to receptors on plant root
cells, leading to changes such as nodule formation and the ability of the bacteria
to enter the root. Inside the root nodule the bacteria carry out the nitrogen fixing
reaction. The symbiotic process depends on communication between bacteria
and plant root through the Nod factor, which is an acylated chitin oligosaccharide
molecule that includes lipid and carbohydrate components. This familiar example
highlights one of the many ways in which glycans play key roles in biological
signaling.
Communication between plant and bacteria during the process of nitrogen fixation. SOURCE:
http://www.glycoforum.gr.jp/science/word/saccharide/SA-A02E.html; accessed June 12, 2012.
Box 1-4
Bitmapped
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INTRODUCTION 21
the same types of feedstocks that are presently obtained from petroleum
or as alternative materials that can be converted directly into plastics with
similar or even superior properties to those of today's synthetic materi-
als. As the ability to engineer polysaccharides and tailor their chemical
structures and properties advances, the capacity to design new biochemi-
cals and materials with properties that are unachievable today also will
greatly expand.
1.2 GENES AND PROTEINS ARE NOT ENOUGH:
THE RICH INFORMATION CONTENT OF GLYCANS
The current view of information flow in biological systems starts
with the nucleic acid genome, which codes for proteins that function as
parts of networks and whose own roles are still being actively studied.
After proteins have been assembled, they are nearly always modified--a
process generically called posttranslational modification. The terminal
stage in this information flow is often the addition of glycans to proteins
(glycosylation), which modulates the proteins' activity. One way of look-
ing at this process is that the instructions in the genome encodes the
properties that will ultimately be observable in an organism (phenotype),
whereas the proteome predicts the phenotype. The glycome, however, is
the phenotype. The system can also be compared to a switchboard, with
the sugars being the "on" and "off" switches or turn pots that modulate
the functions of glycoproteins and other molecules and help control the
activity of the network. Beyond this digital view of biology, glycans also
serve major analog functions, allowing modulating ranges of functions of
glycoproteins and other molecules as well as metabolic circuits and net-
works. Working backward to understand biological systems will require
starting with glycobiology, just as working forward requires starting with
genomics.
Unlike nucleic acids and proteins, the structures of glycans are not
"hard-wired" in the genome. Because of the multiple linkages that sug-
ars can engage in that produce isomers and branching patterns, glycan
structures cannot accurately be described as simple linear sequences of
building blocks. Rather, a glycan's most basic structure must be described
in three dimensions. Because glycan structures are not template encoded,
they are plastic, reflecting myriad factors determined by cellular metabo-
lism, cell type, developmental stage, nutrient availability, other cues from
the cell's environment (Rudd and Dwek 1997; Varki et al. 2009), and
stochastic events. As a result, the potential information content of gly-
cosylation is far greater than for all the other types of posttranslational
protein modifications combined. It is precisely this enormous diversity
and plasticity that are critical to the many biological functions of glycans,
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22 TRANSFORMING GLYCOSCIENCE
particularly their modulation of glycoprotein activity or localization and
their roles in mediating cell-cell or cell-matrix interactions that are key
to both normal physiological development and diseases such as cancer.
1.3 HOW GLYCOSCIENCE BUILDS ON
GENOMICS AND PROTEOMICS
Today, the glycoscience field is at a place similar to where genetics
was at the conception of the Human Genome Project. At that time there
was enough of an understanding of genetics to know that a concerted
effort to sequence the human genome would lead to both fundamental
advances in our understanding of genetics and practical applications that
would benefit all fields of science. When this enormous effort began in
the 1990s, many scientists questioned if it was even feasible to sequence
the 3 billion bases in a human genome. Ten years and $2 billion later, the
Human Genome Project not only had sequenced a single human genome
but had also spawned a technological revolution that today makes it
possible to sequence a human genome in only a week at a cost of $1,000.
Similarly, the cost of identifying a single nucleotide polymorphism (SNP),
a commonly used marker for genetic traits such as disease, fell from $1
per SNP to $0.004 per SNP, opening the door to a wide range of biological
questions inconceivable even 10 years ago.
Another impact of the Human Genome Project has been the democ-
ratization of genomics. The result is a revolution in our understanding
of genetics that spans the simplest single-celled organisms to the charac-
terization of human variation and disease. Sequencing instruments used
to be huge and expensive, and, as a result, sequencing was done only at
regional centers. Today, sequencing instruments can sit on a benchtop in
any laboratory. Now, any laboratory can get DNA sequenced; computer
programs can predict structures from sequences for DNA, RNA, and pro-
teins; and DNA or RNA can be ordered online and delivered the next day.
How did all of this happen in such a short period of time? The trans-
formation of genomics, and the generation of an entire new industry,
started with the research community issuing a grand challenge that was
a huge leap, something beyond any technical capability available at the
time. In the end, the tools that were developed to meet this grand challenge now
enable and drive the science. The tools of genomics have democratized the
field in such a way that thousands of laboratories are now able to ask and
address questions that were previously the realm of only a few specialized
facilities. Any scientist interested in getting sequence information can do
so. Today, because of incredible success at developing sequencing tools,
the real cost of sequencing a genome is dominated by informatics, not by
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INTRODUCTION 23
the physical process of sequencing. Making sense of genomic data costs
far more than acquiring the data.
Glycoscience needs to similarly catalyze its transformation from the
realm of a few specialists to a core science practiced by many. To accom-
plish this transformation, new technologies are needed to thoroughly
characterize glycomolecules and synthesize them. Both genomics and
proteomics have methods for automated synthesis, sequencing, and
amplification. The emerging field of glycomics does not. There are large
libraries of genes and proteins available for study but only small librar-
ies of glycans and glycoconjugates. Genetic manipulation of genes and
proteins is easy but is hard for glycans and glycoconjugates. Finally, the
number of enzymes available for manipulating genes and proteins is far
larger than the number of glycosidases and glycosyltransferases available.
Learning from the experience of genomics, glycomics will need many new
and sophisticated informatics solutions to stay abreast of technological
developments and avoid the bottlenecks that now limit the advances that
come from modern genomics and proteomics.
1.4 WHY NOW? THE CASE FOR CHANGE
To fully understand the workings of living organisms and to fully
realize the promise of genomics and proteomics, it will be imperative that
science now turn its efforts to deciphering the complexity of glycomics.
Unless attention is paid to glycans, a major component of biology will be
missed. Glycoscience cannot be overlooked. Without a better understand-
ing of the glycome, a clear understanding of cancer, infectious diseases,
and the immune response will not be possible. Glycoscience knowledge
will be similarly needed in the exploration of improved biofuels and alter-
native sources of carbohydrate-based energy and in the development of
carbohydrate-based materials with functional new properties. It will not
be possible to take full advantage of the revolution in genomics and real-
ize the full potential of the Human Genome Project unless close attention
is given to glycomics and how cells make and use the myriad complex
glycans that decorate their surfaces. At the same time, advances in genom-
ics resulting from the Human Genome Project provide a major opportu-
nity to understand how mutations alter glycan pathways with functional
consequences. Indeed, the time is right for the glycoscience community to
initiate an undertaking that leads those conducting biological studies to
seriously consider incorporating glycoscience into their work.
Several recent advances make now the time to examine challenges
and opportunities in glycoscience and outline a possible roadmap for-
ward. In health, for example, changes in glycosylation are common in
tumor cells and specific glycans have been identified as biomarkers for
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24 TRANSFORMING GLYCOSCIENCE
a variety of cancers (Adamczyk et al. 2012). In some cases, this informa-
tion is being combined with array technologies to provide a base from
which to explore key questions in cancer biology. Do particular glycosyl-
ation changes play a role in cancer outcome? Which glycans can serve as
the most effective biomarkers for different stages and different types of
cancer?
In 2011, the U.S. Department of Energy released an update to the
Billion-Ton Study, which re-emphasized the significance of biomass feed-
stocks from non-food crops for energy and materials (DOE 2011). Many
of the energy-rich, non-food crops require the conversion of recalcitrant
cellulose into useful chemical precursors. Discoveries in the biological
pathways by which plant cell walls are synthesized and deconstructed
are similarly providing a compelling base from which to further advance
the applications of glycoscience to these fields.
Just as studies of nucleic acids and proteins rely on a suite of tools
that allow a broad range of researchers to effectively investigate these
molecules, so too does glycoscience rely on its own toolkit. Over the past
decade, developments in synthetic and analytical methods such as glycan
microarrays are enabling high-throughput analysis of the interactions of
glycans with proteins, lipids, and other glycan molecules (Rillahan and
Paulson 2011). These data are increasingly being combined into glycan
databases, to share and aggregate research results within the glycoscience
community (Frank and Schloissnig 2010).
Genomics and proteomics have advanced rapidly. Glycoscience and
glycomics also have made strides in enabling scientists to understand the
role that glycans play in biological systems. Glycoscience researchers have
been developing a fundamental knowledge base that can be utilized to
help address many of today's major research problems. This knowledge
base, when combined with the current set of available tools to probe gly-
can structure and function, is a powerful resource to better understand
human, plant, and microbial biology.
Glycoscience has, until recently, been explored by only a small group
of experts, working with more limited information and resources than
are available in fields such as genomics and proteomics. What is known
about glycoscience and glycomics, the study of the complete set of glycans
in an organism, is still incomplete. But the knowledge currently available
now makes it possible to integrate glycoscience broadly into the fields of
human health, energy, and materials science, and the set of tools, while
not perfect, provides a base to enable further development and discovery.
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INTRODUCTION 25
1.5 CHARGE TO THE COMMITTEE
Recognizing that glycoscience presents a frontier for discoveries
across many fields, the National Institutes of Health, Food and Drug
Administration, U.S. Department of Energy, and National Science Foun-
dation asked the National Research Council to convene a committee to
explore advances in glycoscience and challenges that must be overcome to
move the field forward. The committee was also tasked with articulating
a roadmap and a vision for future development of the field (see Box 1-5).
The committee deliberated at three in-person meetings and held
numerous teleconferences to address its charge and produce the present
BOX 1-5
Statement of Task
The National Research Council of the National Academy of Sciences will con-
vene an ad hoc committee to assess the importance and impact of glycoscience
and glycomics. Glycoscience is the confluence of scientific disciplines that study
complex glycans and their relationships to other molecules. Glycans are involved in
all phases of life, and an improved understanding could significantly impact diverse
sectors of society, including health and energy. While genomics and proteomics
have produced unparalleled discoveries that have advanced the understanding of
biological processes, the picture these present is incomplete. Glycoscience and
glycomics, the systematic analysis and characterization of the structure and func-
tion of glycans synthesized by a cell, tissue, or organism, could be a critical next
step in building on genomics and proteomics, linking gene function to an observed
phenotype, and decoding the molecular makeup of an organism.
In order to realize the potential of glycoscience and glycomics to build on
genomics and proteomics and forge major new roads of discovery, the National
Research Council of the National Academy of Sciences will convene an ad hoc
committee to:
· C
onduct an in-depth analysis of the current state of research in glycoscience
and glycomics in the U.S.;
· Compare current U.S. and international research efforts in glycoscience;
· Discuss key challenges to the growth and development of the field of glycosci-
ence and glycomics;
· Develop a roadmap with concrete research goals to significantly advance gly-
coscience and glycomics in the U.S., including the identification of metrics that
may be used to help assess efforts to achieve these goals and objectives; and
· Articulate a unified vision for the field of glycoscience and glycomics.
The ad hoc committee will conduct workshops and other data-gathering activi-
ties to inform its findings and conclusions, which will be provided in the form of a
consensus report.
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26 TRANSFORMING GLYCOSCIENCE
report. In addition, the committee convened the Workshop on the Future
of Glycoscience in January 2012, which brought together approximately
75 glycoscientists and scientific thought leaders with expertise in biology,
chemistry, and materials science to discuss the field and its opportuni-
ties and needs. The workshop agenda and participant list are provided
in Appendix C. The committee also solicited input from the broader
scientific community through its public website, which included several
questions to inform the study process. These questions are provided in
Appendix D, along with further information on the feedback received and
the individuals who shared their thoughts with the committee. This report
does not focus on the roles of carbohydrates as food sources and nutri-
tional supplements. Although these are important areas to be explored,
they were outside the scope of the committee's study and outside the
expertise of the committee's members.
1.6 ORGANIZATION OF THE REPORT
Chapter 2 discusses current glycoscience research efforts in the United
States and worldwide. This general baseline helps inform the rest of the
report, which lays out a vision for the future of the field. The chapter pro-
vides a brief overview of key messages arising from the committee's data
gathering, with further details and examples included in Appendix B.
In Chapter 3 the committee discusses how glycoscience is embedded in
the key areas of health, energy, and materials science--areas that help
illustrate the breadth and impact of glycoscience as a discipline. In Chap-
ter 4 the committee poses a set of scientific questions and opportunities
designed to illustrate more concretely how new glycoscience knowledge
would contribute to answering relevant scientific questions in these fields.
These questions are not meant to be comprehensive but rather to provide
examples of scientific challenges that, if solved, would yield important
basic and applied knowledge. Chapter 5 considers the toolkit for glyco-
science in such areas as synthesis, analysis, and informatics. These tools
are integral to studying glycoscience and will be needed to successfully
address the types of challenges described previously. Finally, Chapter 6
presents the committee's conclusions and recommendations. In conjunc-
tion with each recommendation, the committee suggests several 5- and
10-year goals whose accomplishment would significantly advance the
field. Together, these goals comprise a roadmap to help enable glycosci-
ence to forge new roads of discovery.
The introductory and concluding chapters of this report are written
with a general audience in mind. Chapters 3 and 4, which delve more
deeply into the myriad ways that glycans contribute to the three focus
areas of health, energy, and materials, presume a basic level of scientific
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INTRODUCTION 27
familiarity, although of necessity do not cover each topic in detail. Chap-
ter 5, which describes the current scientific toolkit for studying glycans,
is written largely for the scientific community and for those who have
primary responsibility for shaping research programs and directions. The
committee's assessment of this toolkit and of the needs and gaps remain-
ing to advance the field is encapsulated in the report's concluding chapter,
which lays out a glycoscience roadmap and research goals. Appendixes
to the report contain committee member biographies (Appendix A) and
additional information on the committee's data-gathering efforts (Appen-
dixes B, C, and D). A glossary of terms also is included (Appendix E).
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