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PBIO 25th AnniversarySecuring the world's food supply in a changing climate may be one of the biggest challenges we face in this century. In six of the past eight years, the human race consumed more corn, wheat, and rice than it grew.

Every day, 18,000 children under age five die of hunger and malnutrition. Almost all of them live in developing countries, the very countries most vulnerable to climate change.

Understanding the molecular underpinnings of how plants adapt to challenging environments and defend themselves against insects and fungal infections will be crucial to ensuring the world’s food supply into the future, making basic plant research more important than ever.

Founded 25 years ago, the Salk’s Plant Biology Laboratory is home to some of the world’s leading plant biologists. Their groundbreaking research profoundly impacts many areas of science, from agriculture to stem cell research, from tumor biology to drug development.

Joanne Chory Lab"Our lab is interested in identifying the mechanisms that plants use to respond to changes in their environment, particularly light. Our hope is that by discovering the molecular triggers that determine whether a plant matures into a spindly or robust specimen, we can contribute to efforts to increase crop yield and alleviate hunger."

Plants by nature may be rooted to one spot, but they are remarkably adept at making the most of their digs. Activating a complex series of molecular switches that regulate their growth patterns, they literally seek their place in the sun by reacting to changes in their surroundings in ways that maximize their chances for survival.

Chory and her team have recently identified two pathways that govern different aspects of plant growth. For light-loving plants, competing with larger flora for a share of the sun can lead to so-called shade avoidance syndrome—a set of responses in which they expend their growth resources toward stem elongation rather than bulking up harvestable portions such as leaves and seeds. Using the reference plant Arabidopsis thaliana, Chory's group identified a series of genes that plays roles in the shade response and identified one that encoded a new enzyme. She and her colleagues determined that the enzyme uses the amino acid tryptophan to synthesize auxin, a hormone that regulates plant growth. This pathway is rapidly deployed to synthesize auxin at the high levels required to initiate the multiple changes in body plan associated with shade avoidance. Despite auxin's importance for plant growth and development, the details of how it is synthesized have puzzled plant biologists. Multiple biochemical pathways for the production of auxin have been proposed, but the specific function of each pathway and how they all intersect is not known. Now the role of at least one pathway has become clearer.

Starlight, not daylight, lies at the heart of another recent discovery by Chory and her colleagues. At least since Charles Darwin, scientists have known that many plants grow in regular nightly spurts, with plant stems elongating fastest in the hours just before dawn. Chory's lab has identified the genes controlling those bursts of rhythmic growth. They found that expression of a large number of genes scattered around the Arabidopsis genome dealing with hormone biosynthesis, hormone signaling, and hormone metabolism are all tightly correlated with rhythmic plant growth.

These discoveries could eventually allow scientists to design crops that can grow substantially faster and produce more food than the most productive varieties today.

Ecker Lab"Nature vs. nurture, genes vs. environment—what is more important? My group is interested in understanding the roles of genetic and 'epigenetic' processes in cell growth and development. By understanding how the genome and epigenome talk to one another, we hope to be able to untangle the complexity of gene regulatory processes that underlie development and disease in plants and humans."

Our view of heredity has largely been written in the language of DNA, but recent discoveries in a field known as epigenetics—the study of heritable changes in gene function that occur without changing the letters of the DNA alphabet—show that how a cell "reads" those letters is critical. Adding molecules such as methyl groups to the backbone of DNA can change how genes interact with the cell's transcribing machinery and hand cells an additional tool to fine-tune gene expression. The genomes of higher eukaryotes are peppered with modifications, but until scientists were able to take a detailed look at the whole genome, there was no way of knowing whether a particular chemical tag was critical or not.

Ecker and his team pioneered new technologies that allowed them to capture the genomewide DNA methylation pattern of the plant Arabidopsis thaliana and chart its effect on the activity of any of Arabidopsis's roughly 30,000 genes. Cells employ a whole army of enzymes that add methyl groups at specific sites, maintain established patterns, or remove undesirable methyl groups. When Ecker and his colleagues compared normal cells with cells lacking different combinations of these enzymes, they discovered that cells put a lot of effort into keeping certain areas of the genome methylation-free. On the flipside, they found that when they inactivated a whole class of methylases, a different type of methylase would step into the breach for the missing ones. This finding is relevant for a new class of cancer drugs that work by changing the methylation pattern in tumor cells.

Being able to study the epigenome in great detail and in its entirety will provide researchers with a better understanding of plant productivity and stress resistance, the dynamics of the human genome, stem cells' capacity to self-renew, and how epigenetic factors contribute to the development of tumors and disease. Ecker and his team are already looking into how methylation affects the development of human stem cells as they differentiate into other types of cells.

"The expression of genetic information within each cell must be precisely regulated for normal development, as is evident by the numerous diseases and developmental defects associated with aberrant gene expression. One layer of gene regulation involves the addition of chemical groups, or 'epigenetic modifications,' to chromatin, a combination of DNA and proteins in a cell's nucleus. I am interested in understanding how these chemical instructions are recognized and translated into stable gene expression patterns."

In plants, mammals and other eukaryotic organisms, the addition of epigenetic modifications to both DNA and histones (proteins that package and order DNA) are known to influence the expression of the underlying genes and to play critical roles in diverse biological processes, including cellular differentiation, development and the maintenance of genome integrity. However, compared to the amount of data generated over the last few decades regarding the proteins and pathways responsible for establishing, maintaining and removing epigenetic modifications, relatively little is known about how epigenetic modifications actually lead to changes in gene expression and chromatin structure.

The plant Arabidopsis thaliana provides an ideal system to study epigenetic processes. It is genetically malleable, highly amenable to whole genome analyses and, unlike mammals, is highly tolerant of dramatic changes to its epigenetic code. In addition, plants and mammals share many of the key proteins and pathways involved in establishing and maintaining epigenetic modifications, so findings in plants may be applicable to animals and humans. To gain a better understanding of the cascade of events that lead from the addition or removal of a particular epigenetic modification into a change in gene expression, Law focuses on the characterization of several newly identified families of chromatin binding proteins. By employing genetic, biochemical and genomic approaches, she aims to determine the epigenetic modifications recognized by these protein families, identify their interacting partners and determine their effects on gene expression and higher order chromatin structure. This will provide a holistic view of how epigenetic modifications control gene expression.

Such studies will begin filling a gap in our current understanding of epigenetic gene regulation and will greatly enhance our ability to understand and control the expression of existing and newly introduced genes, which has broad implications in both agriculture and gene therapy.