A Paradigm for Understanding Plants – Rom, 23.11.2006 Forum (englisch)
USA - USA/Kanada
Elliot Meyerowitz und Christopher Somerville
Balzan Preis 2006 für Molekulargenetik der Pflanzen
Für ihren gemeinsamen Einsatz zur Etablierung von Arabidopsis als Modell für die Erforschung der molekularen Genetik von Pflanzen. Diese gemeinsame Leistung hat weitreichende Konsequenzen sowohl für die Grundlagenforschung wie auch für potenzielle Anwendungen auf diesem Gebiet.
“For an experiment one needs a plant, a flower pot with earth, and a question.” (Karl von Goebel, quoted in Lloyd, F.E., 1935, Plant Physiol 10, 206).
Plants are of fundamental importance to human life and well-being, not only as food, but also as sources of much of our building materials, fiber, fabrics, dyes, pharmaceuticals, flowers, and even of the oxygen that we breathe. Indeed, much of what we think of as “nature” is communities of plants. It is, therefore, remarkable how much remains to be learned about the basic biology of plants by comparison with most other types of organisms. Although the quest for new plants once inspired explorers, during the latter half of the last century basic research on plant biology fell out of favor. Today, scant attention is devoted to the study of plants in schools and universities in the developed world. Only about 1% of investigator-initiated peer-reviewed funding for biological research in the U.S. goes to plant research. Therefore, we greatly appreciate the recognition by the Balzan foundation of the importance of our field of plant molecular genetics.
We share the 2006 Balzan Prize for stimulating the development of an experimental framework that has greatly facilitated the acquisition of human knowledge about most aspects of plant growth and development. That framework is organized around the concept of focusing a high level of scientific investment on a single, carefully chosen, model organism that is representative of a large number of other organisms. The expectation is that understanding one model organism deeply will greatly facilitate subsequent or parallel investigations of all other organisms of the same type. Because flowering plants evolved from a common ancestor only about 150 million years ago, all of the roughly 250,000 species of flowering plants are closely related and share a common set of genes. We were among the first of a small group of scientists to champion the use of a small mustard species called Arabidopsis thaliana that has become the most widely used experimental plant today.
When we began working with Arabidopsis about twenty-five years ago, relatively little was known about eukaryotic genes and proteins. Most plant biologists performed experiments on plants that were of interest because of their value as food crops or because of some peculiarity that was useful for a specific kind of experiment. No higher plant had been chosen for use based only on its utility as a model organism. We had both received training in other aspects of biology (E. coli and Drosophila genetics), where the value of model organisms was well-known. Thus, when we became interested in plant biology in the late 1970s, we were drawn to the idea of developing a model plant. We independently settled on Arabidopsis because preliminary experiments by George Redei and others indicated that it had the kinds of properties that were desirable in a model plant. In particular, it was small, easy to grow, self-fertile, diploid, and rapid cycling. It was also closely related to many of the most important food plants in the world. We initially began communicating about technical issues such as how to carry out basic genetic studies with Arabidopsis but, upon the discovery that we had common values and goals, soon began working together to encourage development of the field.
Our contributions to the development of the Arabidopsis community have several dimensions. First, we have used Arabidopsis to make a series of discoveries in plant development and biochemistry. Our approximately 400 research papers provide worked examples for the scientific community; colleagues were encouraged to adopt Arabidopsis because, as we and others showed, it allowed more rapid progress than was available with other experimental systems. Secondly, we collectively trained nearly 150 graduate students, postdocs and visiting scientists who carried their expertise to institutions around the world where they continued their work with Arabidopsis. We encouraged our students and postdocs to take projects with them when they left our labs, thereby facilitating their subsequent success, and the list of our former students and postdocs includes many of the most successful young plant scientists. Thirdly, we invested large amounts of time and effort creating scientific infrastructure. We participated in the organization of scientific meetings, the founding of new journals, the development of internet communication mechanisms, the establishment of stock centers, the writing of reports to funding agencies around the world, the establishment of databases, and the allocation of government funds for support of research. We initiated the development of genetic maps, mutagenized populations, clone libraries, large surveys of DNA sequences, and ultimately, we convened the international committee that managed the sequencing of the complete genome or Arabidopsis.
As a result of our work and that of many other like-minded scientists and administrators, the community of Arabidopsis researchers entered a „golden age“ of discovery in plant biology. Problems that were intractable for decades began yielding to the application of modern methods in molecular and cellular biology. The formula for much of this success was conceptually simple: isolate a mutation that affects the process or structure of interest, clone the gene, find out where and when it is expressed, where the gene product is located, what it does and what it interacts with, directly or indirectly. This approach, started in earnest in the 1990s, has led to detailed molecular models of flower, root, and embryo development, to a molecular-level understanding of the synthesis and perception of plant hormones, to understanding the mechanisms of biotic and abiotic stress tolerance, and to a detailed understanding of circadian rhythms, chromosome behavior, chromatin, and many aspects of metabolism and cell biology. Many of the classical problems of plant biology have thus been solved.
Furthermore, in 2000 the sequence of the genome of Arabidopsis was completed to a very high standard of accuracy and annotation, making it the first known plant genome, and one of the first known genome sequences of a eukaryote. This resource, as with all of the others, was made immediately and freely available to all researchers and led directly to yet another series of advances in the understanding of chromosome structure and evolution, as well as to an enormous change in the rate at which genetic discoveries were made. These resources democratized basic research in plant biology because they reduced the technical difficulties associated with performing complex genetic manipulations of Arabidopsis and made knowledge freely accessible. Thus, small laboratories are now able to undertake experiments that previously were only possible in a small number of laboratories with sizeable resources. Of course we cannot take credit for all of this progress alone, not by any means. A number of colleagues have also contributed in many important ways. In particular, in the early days when Arabidopsis was being established as a model system, there were critical contributions by Fred Ausubel, Michel Caboche, Joanne Chory, Ron Davis, Caroline Dean, Liz Dennis, Joe Ecker, Ken Feldman, Gerry Fink, Dick Flavell, Howard Goodman, Maarten Koornneef, Dave Meinke, Marc van Montagu, Jim Peacock, Shauna Somerville, and many others.
It was also fortunate for plant biology that a number of grant administrators around the world realized the potential of Arabidopsis at an early stage, and provided both financial and administrative support not only for individual research projects but also for workshops and community-wide resources such as the stock centers, databases and the EST projects. Some of the U.S. administrators who deserve special mention in this respect are Machi Dilworth, Delill Nasser and Mary Clutter of the National Science Foundation and Bob Rabson and Greg Dilworth of the Department of Energy. Étienne Magnien of the Commission of the European Communities, Directorate of Biology, played a similarly influential role in Europe.
Overall, the result of the introduction of Arabidopsis thaliana as a model system for plant biology, and the adoption of this model by hundreds of research laboratories world-wide, has been an enormous growth of our knowledge of plants, including the understanding of molecular mechanisms of plant cell division, and of cell-cell communication in plant development and in response to pathogens. Much has been learned also about the interactions of plants with their environments. And, the dream that study of a small and humble weed in university laboratories would teach us what we need to know for the future of agriculture has been fulfilled, as Arabidopsis work now serves as the basis for many of the modern advances in crop improvement. Furthermore, the path taken in establishing Arabidopsis as a model system for all plants has been used as blueprint to develop the necessary knowledge and resources for many other plants, such as rice, maize, poplar, tomato, soybean, and Medicago, all of which now have active and successful genome projects.
There is more to be done, however. At the level of fundamental science we are at a new crossroads, where the amount of information we have gained is so large that no one person can internalize it. The structure and protein coding capacity of each of the nearly 30,000 Arabidopsis genes is known, but the genes are only a list of parts, with no assembly instructions. They function only in the context of astoundingly complex cells, with membranes, organelles, dynamic protein structures, and metabolic pathways that must all be in place before genomic information can be read out and used. And in an Arabidopsis plant, as in any complex multicellular organism, there are hundreds of thousands of cells, each communicating with its neighbors via short-range signals such as the direct communication through plasmodesmata, and local communication with small peptide ligands and transmembrane receptor kinases. Each is also connected to more distant cells, with signals of the standard plant hormones, and of metabolites such as sugars that carry information through the plant. We need a fundamental change in the way we treat this information. Our contribution, and that of our colleagues in the Arabidopsis world, has been to speed and organize the gathering of data about the molecular mechanisms of plants. The time has now come to speed and organize the use of this information by developing a mathematical and computational infrastructure that will allow vast amounts of specific information about plants at the atomic, molecular, organelle, cell, and whole plant levels to be integrated into working models that can make specific experimental predictions. We envision that a future generation of biologists will have access to a “virtual plant” in which a computer model will integrate detailed molecular information to create a dynamic simulation of a plant throughout its lifecycle. We recognize that such a vision seems impractical at present. However, one of the things that we have learned during the past twenty-five years is the importance of setting seemingly impossible goals as a stimulus to scientific creativity and ambition.
The widespread adoption of Arabidopsis as a model organism also has important and timely consequences in agriculture, forestry and energy. The continuing expansion of the human population will continue to create pressures on the world’s natural resources. The advances in breeding and agronomy of the green revolution, which have spared hundreds of millions of lives and have saved billions of acres from conversion to agriculture, will need to be extended by the rational application of knowledge to plant improvement. The tools of discovery that have been enabled by the adoption of Arabidopsis are the core resource for the second green revolution, which is now underway. Discoveries concerning the basis of plant mineral acquisition and storage are being used to develop plants that will address the largest health problem for almost a billion people. Similarly, advances in understanding plant vitamin metabolism, plant pest and pathogen tolerance, drought and salt stress, fruit development, and basic growth processes will enable the rational improvement of both the amount and nutritional quality of the staples that feed the world. As natural solar energy storage devices, plants can also be a major carbon-neutral source of the energy needed for industry and agriculture in the future. We are using vast amounts of fossil fuels to provide the energy necessary to grow and transport our food, and these fuels are not only a limited resource, but also the major source of carbon dioxide that is accumulating in the atmosphere and leading to global warming. We are thus in a feedback loop in which fossil fuel is needed to grow our crops, but its use is changing the atmosphere and climate upon which our agricultural systems are based. Advances in understanding basic plant growth and development offer one of the few options for breaking our dependency on fossil fuels and developing sustainable and renewable sources of carbon-neutral energy. We believe that these challenges can be met by the continued application of science and technology.
Our experience in helping to create and mobilize the Arabidopsis community is tangible evidence that large numbers of scientists can be organized to pursue a collective vision across national boundaries and a broad variety of motivations and interests. It is our hope that other scientists will be encouraged by our experience to go beyond managing a single laboratory and will endeavor to encourage and facilitate the work of larger groups of colleagues to undertake collective action on the many basic and applied problems that require community-level eng.