Introduction
Plants are the foundation for the human food supply and in the
future will provide more and more of the raw materials required
for industry (e.g. fuel, biopolymers, oils, textiles, pharmaceuticals).
Our ability to feed the world's growing population, and to do
so in a sustainable way, is directly dependent upon our ability
to genetically engineer plants. Until recently, the only tools
for genetically-modifying plants were those of traditional breeding.
However, in the past 10 years, powerful new tools of molecular
biology have revolutionized how we perform plant breeding, and
have also opened up new methods for plant improvement through
the application of molecular genetics. It is estimated that in
the next 5 years over 50% of the crop produced in the US will
be genetically engineered (USDA forecast). Recent improvements
in DNA sequence acquisition and analysis will likewise expand
our abilities to improve plants, but to a much greater extent.
By the year 2001 the entire genome of a plant will be sequenced
- that of Arabidopsis , a small weed from the mustard family.
This will be the first time that scientists will have the complete
genetic blueprint of a plant. The challenge will then be to understand
what each of those genes does and how the genes from Arabidopsis
relate to those of other plant species -- especially crop
plants.
Plant genomics is a newly emerging field that holds the promise
of describing the entire genetic repertoire of plants. The information
derived from studies of plant genomics will help us understand
how genes enable a plant to carry out its functions as a living
organism, and how the diversity of functions in all plants are
related to simple changes in individual genomes. Plant genomics
ultimately may be used to modify genetically plants for optimal
performance in different biological, ecological and cultural environments
for the benefit of humans and the environment. In addition, the
analysis of plant genes provides an important link with parallel
work in animals and microbes through comparative genomic analyses
of gene structure, function and evolution in different organismal
kingdoms.
Cornell's Current Role in Plant Genomics
Cornell University is an internationally recognized leader in
plant genetics and molecular biology. It was at Cornell that the
molecular basis of sexual mating (incompatibility) was first discovered,
transposable elements were identified, and much of the research
now being conducted on crop plant genomes was initiated. The first
molecular maps for plants were first constructed here as were
the foundations of molecular breeding now being exploited throughout
the world.
Cornell draws its excellence, not only from academic departments
in both the College of Agriculture and Life Sciences and the College
of Arts & Sciences, but also from the presence of two prestigious
plant research institutions on campus -- The Boyce Thompson Institute
and the USDA/ARS Plant Soil and Nutrition Laboratory. Both of
these institutions have identified plant genomics as their future
thrust areas and are likely to be magnets for additional funding
in this area.
Because of its international reputation, top notch faculty, graduate
students and postdoctoral associates, Cornell is positioned to
be the lead institution in plant genomics. The field is exploding
with new technologies and discoveries, spurred and sustained by
large increments in federal funding (e.g. NSF and USDA funding
in plant genomics is expected to exceed $100 million in the next
2 years). This is evidence that our legislators place value on
the field, primarily because of its role in enhancing the competitive
position of the US in Science and Technology. The Institute for
Genome Research (TIGR) has selected Cornell as its primary university
partner to develop a major thrust in plant EST sequencing and
comparative genomics. Private foundations and international agencies
(Rockefeller, Ford, McKnight, the World Bank) are interested in
supporting the application of genomics to problems of international
agriculture. The private sector has invested heavily in this area
over the last few years, with an eye to the impact of genomics
on agriculture and medicine. At this time, many companies involved
in genomics research are looking to the academic community for
new ideas about how to use the vast quantities of genomic information
they have generated. It is timely that Cornell take the necessary
steps to ensure that the university is well-positioned to take
advantage of the expanded research and funding opportunities in
the area of genomics.
Because of the dramatic increase in the volume and type of data
generated by genomics research, interpretation of the underlying
biological meaning also requires more expansive alliances outside
of the traditional areas of Plant Sciences. We must develop the
intellectual environment that fosters interdisciplinary interaction
among faculty across departments and colleges in order to look
beyond established ways of thinking about biological questions.
We must also develop the capacity to train graduate and undergraduate
students to think creatively about significant biological problems
in an increasingly interactive and information-rich environment.
Cornell is uniquely situated to bring together expertise in these
diverse areas, and to build an intellectual and funding environment
that will be the envy of other institutions. As demonstrated by
the strategic plans for the various thrust areas in this Genomics
Initiative, the faculty is willing and anxious to make this a
reality. If we fail to meet these challenges, the best faculty
and students will go elsewhere, taking the bulk of the financial
resources with them.
Thrust Areas
Deciphering the plant genome is an enormous task that will require
participation and collaboration of scientists around the world.
Cornell needs to pick out key areas where it can be the world
leader. Based on our existing strengths and anticipating what
issues will be important in the future, we recommend that Cornell
invest in three thrust areas in Plant Genomics:
Plant Metabolic Pathways
Deciphering control of synthesis, accumulation and function
of primary and secondary metabolites. Primary compounds
(e.g. sugars, cellulose, organic acids) provide plants with much
of their nutritional and industrial value. Secondary compounds
are unique, often species-specific, compounds that provide plants
with defense against insects and diseases and that make plants
such a valuable source of new pharmaceuticals (e.g. taxol). Only
a few of the pathways that produce secondary compounds have been
elucidated; thousands of others remain to be examined. At issue
is understanding how the diverse array of genes that encode the
components of these pathways evolved. If we can unravel the genetic
program by which plants regulate the production, storage and use
of these compounds, we will be able to i) manipulate the nutritional
value of plant-derived foods, ii) enhance plant defense against
pests and parasites, and iii) use plants as bioreactors to produce
important plant-derived compounds.
Molecular Diversity of Plants
Evaluating, preserving and utilizing natural biodiversity
in plants. Biology is unique as a science because organisms
have heritable characteristics based on genes that are both stable
and predictable and yet maintain the ability to mutate and evolve.
The history of organic life is a history of the evolution of genes
and genotypes and of their relationship to each other and to the
environment. Reduction to the molecular level in biology has been
enormously successful in providing new insights into the ways
in which changes in gene and genome structure lead to new forms
and functions. By focussing on plant molecular diversity, we aim
to explore, utilize and protect the processes that have produced
the diversity of life forms present on earth.
In agriculture, we face a particularly serious dilemma. Human
existence depends on the cultivation of a few highly productive
crop species. However, much of the genetic variation on which
the future of agriculture depends is vanishing. As wild habitats
of our ancestral crop relatives gradually disappear, we lose the
genetic potential accrued over millions of years of evolution.
Without the genetic variation provided by nature it is unlikely
that humans can keep pace with the demand for increased agricultural
outputs and agricultural production with less environmental impacts.
Moreover, plants, and their unique secondary compounds, are being
viewed more and more as a new source of novel pharmaceutical and
therapeutic compounds. A focus on biodiversity in plants, both
genetic and chemical, would complement current work in plant genomics
and would dovetail with a thrust in primary/secondary metabolism.
The molecular and computational expertise that will be developed
as part of a thrust in plant biodiversity, would also lay the
foundation for the University to expand research and training
into broader aspects of genetic biodiversity including animal,
microbial and human diversity, thus connecting with other programs
in genomics on campus.
Plant Genome Informatics
Development of Plant Genome Databases and specialized software:
The USDA Plant Genome Informatics (PGI) Unit in the Plant
Breeding Department currently houses the single largest cluster
of Plant Genome databases in the country. The PGI Unit has developed
and curates five plant genome databases, including GrainGenes
(wheat, rye, barley, oats), RiceGenes (rice and comparative grass
genome displays), SolGenes (tomato, potato, pepper), CabbagePatch
(Brassica), RoseDB (apple), and a related fungal database, RiceBlastDB.
These databases have all been developed using a common software
tool, ACeDB, and they all provide direct links into other public
databases, such as GenBank, GRIN, and Swiss-Prot, as well as links
to each other.
How will developments in these thrusts take advantage of our
existing strengths?
Cornell is a recognized leader in the areas of genetic mapping,
plant gene identification and quantitative trait (QTL) analysis,
plant evolution, molecular breeding,and plant genome database
development, as well as plant molecular biology, pathology and
physiology. Plant Genomics will bring together and enhance our
combined expertise from the Boyce Thompson Institute for Plant
Science (BTI), the USDA's Plant, Soil and Nutrition Laboratory,
and numerous departments from Cornel. Inter-institutional and
inter-departmental interaction in the the design of experiments,
the interpretation of data, and the formulation of grants will
greatly enhance our current efforts in this area of biology.
Linking with other Thrust Areas:
Genomics based research generates very large data sets that are
of interest beyond the immediate group that generated the data.
Today, biologists routinely access data remotely and adapt and
interpret it in light of their own ideas and perspectives. This
means that people with vastly different disciplinary backgrounds
frequently analyze the same datasets, creating fertile ground
for dialogue between traditionally isolated research groups and
creating a need for specially tailored informatics/software tools
designed to answer specific kinds of questions. Significantly,
the kind of data generated by large genomics projects is of interest
to groups as historically separate as CU Ithaca and CU Medical
School, as well as the biological and computational science departments.
The flood of genomic data has the effect of doing away with many
of the artificial barriers that have kept these groups from communicating
in the past. The plant genome initiative will link directly or
indirectly with genomics initiatives dealing with mammalian and
microbial systems because of the fundamental similarity of gene
structure and function in all organisms, and because organisms
share regulatory and metabolic pathways that are subject to similar
evolutionary process. In addition, because many microbes are plant
pathogens or symbionts, discovery efforts in the microbial genomics
area will spur investigations into the plant functions that are
usurped or exploited by these microbes.
The units that would be most impacted by new faculty recruitments
are the departments of Plant Pathology, Plant Breeding and SCAS
(of the College of Agriculture and Life Sciences), Plant Biology,
Genetics & Development, and the L. H. Bailey Hortorium (of
the College of Arts and Sciences), BTI and the U.S. Plant Soil
and Nutrition Lab.
Key faculty positions:
The thrust in Plant Biochemistry and Metabolic Engineering
requires two new hires at Cornell to complement new positions
at the USDA Plant, Soil and Nutrition Laboratory and to establish
preeminence in the area of plants and human health. Currently
Cornell has no Plant Biochemistry on the Ithaca campus. After
Andre Jagendorf retired, the only plant biochemist remaining was
Dr. John Steffens (Plant Breeding). He is currently on a 1 year
leave to a private biotechnology company and it is uncertain whether
he will return to Cornell. If he does not, the position of Assistant/Associate
Professor in Biochemistry of Secondary Metabolism should be refilled
immediately. This position is of central importance to nutrition
in food plants as well as to disease and insect resistance. Metabolic
engineering interlaces with plant genomics in that the metabolic
capacity of a plant can be enhanced or manipulated by a complete
understanding of the repertoire of metabolic pathway options available
within a species or among different plant species.
A second position in Biochemistry of Primary Metabolic Pathways
should be recruited. The study of primary metabolic pathways will
be a key area for discovery in the future; it will impact the
study of basic plant science and provide a starting point for
much novel genetic engineering in plants. The integration of data
from plant genomics with plant growth, development, and physiology
will lead for the first time to the detailed elucidation of complex
primary metabolic pathways. Carbohydrate metabolism and cell wall
assembly are examples of primary metabolic pathways that will
be impacted by the application of "functional genomics".
In particular, the plant cell wall is a novel cellular compartment
in eukaryotes: it is a major sink for biomass and its structure
and function are crucial to plant growth and development. It is
composed of a multitude of carbohydrate and protein constituents,
with more than a hundred different enzymes required for wall assembly
alone, only a small number of which have been characterized in
any detail. The plant cell wall also provides both industrial
products (e.g. timber) and resistance to environmental and biological
stresses (e.g. disease and pests). In addition, modifying the
expression of genes that control wall assembly and composition
is likely to lead to the development of plants with improved agronomic
and nutritional value. It is crucial to be positioned in both
these areas (secondary and primary metabolism) to make the key
discoveries in plant biology and biotechnology.
The U.S. Federal Plant, Soil and Nutrition Laboratory (USPSNL)
is targetting several new hires aimed at improving plant foods
in terms of their nutritional and health promoting properties.
An effort is underway to develop a core group of plant molecular
researchers to improve the nutritional quality of plant foods
through interactions with human nutritionists, plant physiologists
and soil scientists at the USPSNL. The position of Plant Molecular
Geneticistwas recently filled and the USDA laboratory is working
with ARS Administrators to secure funding for one and possibly
two more positions to conduct research at the interface of plant
genomics and human nutrition. These positions will focus on the
molecular biology and biochemistry of metabolic pathways in plants
involved in the biosynthesis and modification of nutritionally
important phytochemicals. Based on the strengths in plant genomics
that we propose to create on campus, the USPSNL is requesting
that the USDA create a USDA-funded genomics center for the improvement
of crop nutritional quality on campus to take advantage of the
Cornell environment and to complement the proposed programs. Recruitment
for all USDA and Cornell positions will be coordinated to ensure
a complementary research team.
The thrust in Plant Molecular Diversity has already
been launched with the opening of two new positions on campus:
1) The Boyce Thompson Institute recently advertised a position
for a plant genomic scientist to study molecular and biochemical
diversity in plants and 2) The College of Agriculture and Life
Sciences has opened a faculty position for a scientist to apply
to tools of genomics to international crop germplasm. These two
new positions (combined with existing faculty strengths) would
provide the underpinnings for a possible new Center for Plant
Biodiversity, which has potential financial backing of the World
Bank, Rockefeller Foundation and private donors. It would be the
first such international program devoted to genomics and biodiversity
and would provide a basis for Cornell to expand into biodiversity
issues of other organisms: humans, microbes, farm animals, etc.
One could invision a set of interlocking centers devoted to biodiversity
and comparative biology in both natural and artificial (e.g.,
agricultural) populations.
To complement these two hires, a third hire in evolutionary and
developmental plant genetics is proposed within the next 1-3 years
(possible department affiliations: Genetics, Hortorium, Plant
Biology or Ecology and Systematics). Such a position would connect
the biodiversity thrusts with other aspects of plant biology and
evolution on campus. The focus of a person in this position would
be to study the evolution of plants and their genes and gene families,
to compare gene evolution in different species (i.e., in polyploids
vs. diploids) and to determine how modifications of the basic
program of plant development lead to diversity (models for this
type of person exist in the world of animal homeobox studies).
This faculty member would also contribute to comparative genomic
studies in plants, microbes and animals. We envision this as a
full-scaled "genomics position" that would require the
computational infrastructure proposed elsewhere to back up this
kind of research.
Plant Genome Informatics
The USDA-ARS has recently created two permanent full-time positions
for bioinformatics professionals to be housed in the Plant Genome
Informatics Unit in the department of Plant Breeding. The first
of these, Plant Genome Data Base Curator, GS-12, has recently
been filled. The position for a Molecular Biologist /Genome Informaticist,
GS-12/13, is currently being advertised. The Plant Genome Informatics
Unit emphasizes the use of genomic information for biological
inquiry and involves the curation of species-specific databases
and application-specific software tools, making it important that
that it be housed in a biology department. This unit provides
a valuable link to computational biology and bioinformatics units
elsewhere on campus.
Teaching: In addition to the USDA employees in the Plant
Genome Informatics Unit, several Plant Breeding faculty members
serve as PI's overseeing database development in the unit. These
faculty members and their USDA counterparts are in the process
of designing two course modules in Bioinformatics, to be offered
for the first time in Fall 1998. One module will be entitled "Bioinformatics:
Accessing Electronic Information Resources" and the other
"Bioinformatics: Approaches to Comparative Genomics".
Ten NT workstations, provided by Intel, are available for the
class on the ground floor of Bradfield Hall. It is expected that
the teaching aspects of Bioinformatics in Biology will be increasingly
managed by a joint effort between professionals in the Theory
Center, Computer Science Department and various Biology units
as the Genomics Initiative on campus expands.
Facilities
The specialized facilities required to move ahead in the area
of plant genomics include an expanded sequencing facility with
more rapid turn-around time and competitive pricing, a service-oriented
bioinformatics and computational biology unit within the biological
sciences with direct links to the Theory Center's super computers,
a large DNA repository for back up of samples used for sequencing,
and micro-array technology facility. We envision that some of
these facilities might be in a centralized location such as the
Biotechnology Center and the Theory Center, connected by a fast-link
to the Medical School and high video conferencing connections
around campus to facilitate communication. Other aspects of this
capability (i.e., bioinformatics units with specialized expertise)
would be best located within the departments where the research
faculty are housed, with electronic links to facilitate communication
among groups. Micro-array technology development is likely to
be housed in the Nanofabrication facility. Several existing, but
under-supported, facilities are also critical for research into
the function of plant genes. These are the plant cell culture
and transformation facility, which houses the "gene gun,"
and the fluorescence microscopy and imaging facility, which houses
a confocal microscope and epifluorescence microscope, both equipped
with sophisticated image analysis software.
Funding Potential
We could expect to compete for federal funds (NSF, USDA, DOE)
that have recently been made available for the new Plant Genome
Initiative, funds from private foundations and international agencies
(Rockefeller, Ford, McKnight, the World Bank) aimed at the application
of genomics to problems of international agriculture, and support
from private sector organizations (Pioneer, DuPont, Monsanto,
Novartis). In addition, we are able to build on the many spin-offs
from the Human Genome Sequencing project (funded by NIH and NSF)
in the form of sequencing, micro-array and computational and analytical
tools. In short, this an area that is likely to attract substantial
funds from multiple sources provided we develop the intellectual
and infrastructure base required to ignite the effort at Cornell.