A Plant's Brainy Balancing Act

Plants don't have a brain. True, they have other winning traits - like the ability to withstand searing summer skies or biting frost (they can't pack up and leave when times get rough). Nevertheless, they lack the neuron-based information processing found in animals, from the single-neuron system found in sea anemones and hydras to the remarkably complex human brain.

Surprisingly, however, what started out for Prof. Gad Galili as a quest to create more nutritious, hardier crops has detoured into research findings that offer a better understanding of the molecules underlying brain function and of a severe human genetic disorder resulting in mental retardation.

A geneticist in the Weizmann Institute's Department of Plant Sciences, Galili focuses on the biochemical machinery that churns out lysine - an amino acid charged with overseeing plant growth and development that is also an essential amino acid in humans, where it serves as a building block of proteins and is vital for proper growth and bone development. Since humans are unable to synthesize lysine they must receive it through their diet, yet cereals and other important crops produce this nutrient in only very small amounts, a fact that is largely responsible for the malnutrition plaguing developing countries and the need to supplement livestock feed with costly additives.

Hoping to boost plant lysine levels, Galili's team began by piecing together the players along this biochemical pathway, asking which compounds are involved and how they interact. They succeeded in pinpointing a key enzyme, known as DHPS, which regulates lysine production. 'The plant doesn't waste any energy,' says Galili. 'Once lysine is present in sufficient amounts, it 'switches off' the DHPS enzyme - a process known as feedback inhibition - preventing further lysine production.' When looking around to see how other organisms tackle this challenge, the team uncovered a counterpart enzyme in bacteria that is less sensitive to feedback inhibition. They decided to genetically insert the gene encoding this bacterial enzyme into a model plant. The result - a significant increase in lysine levels - is currently being used to improve soybean, maize, and canola.

The tightrope walk

But then some of these plants threw a curveball; they started breaking down the extra lysine. It turned out that lysine accumulation consists of both an anabolic, lysine-producing track and a catabolic track, where lysine is broken down into glutamate. The engineered plants were breaking lysine down because excess levels are toxic to the plant. 'It soon became clear that the lysine-glutamate pathway is a master of self-regulation, constituting one of the most highly regulated plant biochemical pathways known,' says Galili. He and others discovered that plants normally maintain the lysine levels needed for protein-based growth and 'housekeeping chores,' while also breaking it down to produce moderate amounts of glutamate. But when under stress, the plant's catabolic machinery switches into overdrive, breaking down far more lysine into glutamate, which is then further modified to produce stress-resistance compounds.

Zeroing in on this catabolic track, Galili has isolated a key gene, known as LKR-SDH, which is equipped with unique regulatory features that may enable lysine catabolism to flow at a slow or rapid pace according to environmental conditions. His findings led to the identification of a counterpart gene in humans that also mediates the production of glutamate (in this context a neurotransmitter playing an essential role in learning, memory, and a host of other tasks - see box). The human gene also keeps lysine levels in check to enable normal brain function. In fact, in April 2000 a team led by Michael Geraghty at the Johns Hopkins University School of Medicine discovered that this gene is mutated in patients with hyperlisinemia, a genetic disorder resulting in mental retardation and other symptoms. 'The discovery of similar catabolic genes in plants and in humans places us in a unique position,' says Galili. 'Studies of this pathway in plants may help reveal how lysine contributes to glutamate production in the brain.'

Nerve Talk

Nerves talk to one another through neurotransmitters - chemical compounds that cross a bridge to neighboring neurons, where they bind to matching receptors. This explains why a recent discovery by a New York University team that plants have receptors for the glutamate neurotransmitter sent ripples of excitement through the scientific community. Researchers had initially thought that plants produce glutamate to protect themselves from herbivores. Indeed, in what may have evolved as a defense strategy, glutamate and many other plant compounds affect human and other mammalian nervous systems, producing a range of hallucinogenic, anesthetic, and other reactions.

However, the discovery of plant receptors for glutamate has triggered an enticing new idea - that similar to its role in humans, glutamate may act as a signaling molecule in plants, conveying information about the environment or regulating developmental processes. In other words, it may underlie an ancient signaling mechanism that has made its way up the evolutionary ladder.

Potential Fields

Personable and brimming with energy, Prof. Gad Galili clearly loves his job. 'When I look at an agricultural field, I see potential,' he confesses. 'My passion is basic science, to understand the mechanisms behind plant function and survival; but I'm also fascinated by implementation, to see how plants can be designed for better nutrition.' Galili believes that future research should include the development of crops with boosted medicinal properties such as antioxidant-rich tomatoes for heart disease patients or for slowing down aging and fighting cancer. Currently collaborating with diverse research teams, including those of Csaba Koncz and Rainer Hoefgen at Germany's Max-Planck Institutes, one of Galili's primary goals is to fine-tune the plant lysine-glutamate pathway, turning off its catabolic machinery at a critical window in time during seed development.

Prof. Galili holds the Bronfman Chair of Plant Science. His research is supported by the Minna James Heineman Stiftung, the Raymund Burton Fund for Plant Genome Research, the Harry and Jeanette Weinberg Center for Plant Molecular Genetics Research, and the Avron-Willstaetter Center for Photosynthesis Research.