Reading Questions: Article 1

  1. When did plants and animals diverge from one another in terms of evolutionary history?
  2. Why is understanding cell receptors important to understanding immune responses?
  3. What were the first receptor genes discovered involved in immunity? What organisms were these genes identified in?
  4. What organisms are being compared in the Science review? Why is using such a large cross-sectionof organisms significant?
  5. What is the FLS2 receptor? Why was its discovery noteworthy?

In Fending Off Diseases, Plants and Animals Are Much the Same, Research Show

Despite having gone their separate ways at least a billion years ago, plants and animals have developed remarkably similar mechanisms for detecting the molecular signatures of infectious organisms. (Credit: Image courtesy of Tree of Life Web Project)

Nov. 20, 2010 — Contrary to long-held beliefs, plants and animals have developed remarkably similar mechanisms for detecting microbial invasions. This holds promise for the future treatment of infectious diseases in humans.It may have been 1 billion years since plants and animals branched apart on the evolutionary tree but down through the ages they have developed strikingly similar mechanisms for detecting microbial invasions and resisting diseases.

This revelation was arrived at over a period of 15 years by teams of researchers from seemingly disparate fields who have used classical genetic studies to unravel the mysteries of disease resistance in plants and animals, according to a historical overview that will appear in the Nov. 19, 2010, issue of the journal Science.

The report, written by Pamela Ronald, a UC Davis plant pathologist, and Bruce Beutler, an immunologist and mammalian geneticist at The Scripps Research Institute, describes how researchers have used common approaches to tease apart the secrets of immunity in species ranging from fruit flies to rice. It also forecasts where future research will lead.

"Increasingly, researchers will be intent on harnessing knowledge of host sensors to advance plant and animal health," said Ronald, who was a co-recipient of the 2008 U.S. Department of Agriculture's National Research Initiative Discovery Award for work on the genetic basis of flood tolerance in rice.

"Some of the resistance mechanisms that researchers will discover will likely serve as new drug targets to control deadly bacteria for which there are currently no effective treatments," she said.

At the heart of this research saga are receptors -- protein molecules usually found on cell membranes -- that recognize and bind to specific molecules on invading organisms, signaling the plant or animal in which the receptor resides to mount an immune response and fend off microbial infection and disease.

Beutler and Ronald have played key roles in this chapter of scientific discovery. In 1995, Ronald identified the first such receptor -- a rice gene known as known as Xa21 – and in 1998, Beutler identified the gene for the first immune receptor in mammals – a mouse gene known as TLR4.

Their overview in Science includes illustrated descriptions of the disease-resistance or immunity pathways in the mouse, Drosophila fruit fly, rice and a common research plant known as Arabidopsis. These represent the immune defense systems of vertebrates, insects, monocotyledons (grass-like plants) and dicotyledons (plants like beans that have two seed leaves.)

The researchers note that plant biologists led the way in discovering receptors that sense and respond to infection. The 1980s brought about an intense hunt for the genes that control production of the receptor proteins, followed by an "avalanche" of newly discovered receptor genes and mechanisms in the 1990s.

Another milestone included discovery in 2000 of the immune receptor in Arabidopsis known as FLS2 -- which demonstrated that a plant receptor could bind to a molecule that is present in many different microbial invaders.

The review also discuses how plant and animal immune responses have evolved through the years and which mechanisms have remained the same.

While the past 15 years have been rich in significant discoveries related to plant and animal immunity, Beutler and Ronald are quick to point out that researchers have just scratched the surface.

"If you think of evolution as a tree and existing plant and animal species as the leaves on the tips of the tree's branches, it is clear that we have examined only a few of those leaves and have only a fragmentary impression of what immune mechanisms exist now and were present in the distant past," said Beutler, an elected member of the U.S. National Academy of Sciences.

He and Ronald predict that, as results from new gene sequencing projects become available, scientists will likely find that some plant and animal species emphasize specific resistance mechanisms while having little use for others.

For example, the researchers point out that the Drosophila's immune system depends on only one immunologically active receptor, known as the Toll receptor, to sense invasion by fungi and gram-positive bacteria. In contrast, Arabidopsis has dozens of sensors to protect against microbial infections and rice has hundreds.

Ronald and Beutler project that many surprises will be uncovered by future research as it probes the disease-resistance mechanisms of other species.The review study was supported with funding from the National Institutes of Health.

Reading Questions: Article 2

  1. Why is programmed cell death important to both plants and animals? What diseases can result from too few cells dying? From too many?
  2. What is TUDOR-SN? What does TUDOR-SN do during programmed cell death? What is meant by TUDOR-SN being evolutionarily conserved?
  3. What are proteases? Caspases? Meta-caspases? How do these relate to TUDOR-SN?
  4. What happens to cells that lack TUDOR-SN? How does the presence of TUDOR-SN contribute to development?
  5. When did TUDOR-SN evolve? Why is programmed cell death important for all multicellular organisms? How does it relate to immune system function?

Cell Death Occurs In Same Way In Plants And Animals

In both plant and animal cells that undergo programmed cell death, the protein TUDOR-SN is broken down. In pollen, from the model plant mouse-ear cress, a reduction in TUDOR-SN leads to fragmentation of DNA (red signal) and premature cell death. (Credit: Photo by Andrei P. Smertenko)

Oct. 21, 2009 — Research has previously assumed that animals and plants developed different genetic programs for cell death. Now an international collaboration of research teams, including one at the Swedish University of Agricultural Sciences, has shown that parts of the genetic programs that determine programmed cell death in plants and animals are actually evolutionarily related and moreover function in a similar way.

The findings were published in Nature Cell Biology October 11.

For plants and animals, and for humans as well, it is important that cells both can develop and die under controlled forms. The process where cells die under such forms is called programmed cell death. Disruptions of this process can lead to various diseases such as cancer, when too few cells die, or neurological disorders such as Parkinson's, when too many cell die.

The findings are published jointly by research teams at SLU (Swedish University of Agricultural Sciences) and the Karolinska Institute, the universities of Durham (UK), Tampere (Finland), and Malaga (Spain) under the direction of Peter Bozhkov, who works at SLU in Uppsala, Sweden. The scientists have performed comparative studies of an evolutionarily conserved protein called TUDOR-SN in cell lines from mice and humans and in the plants norway spruce and mouse-ear cress. In both plant and animal cells that undergo programmed cell death, TUDOR-SN is degraded by specific proteins, so-called proteases.

The proteases in animal cells belong to a family of proteins called caspases, which are enzymes. Plants do not have caspases – instead TUDOR-SN is broken down by so-called meta-caspases, which are assumed to be ancestral to the caspases found in animal cells. For the first time, these scientists have been able to demonstrate that a protein, TUDOR-SN, is degraded by similar proteases in both plant and animal cells and that the cleavage of TUDOR-SN cancel its pro-survival function. The scientists have thereby discovered a further connection between the plant and animal kingdoms. The results now in print will therefore play a major role in future studies of this important protein family.

Cells that lack TUDOR-SN often experience premature programmed cell death. Furthermore, functional studies at the organism level in the model plant mouse-ear cress show that TUDOR-SN is necessary for the development of embryos and pollen. The researchers interpret the results to mean that TUDOR-SN is important in preventing programmed cell death from being activated in cells that are to remain alive.

The research teams maintain that the findings indicate that programmed cell death was established early on in evolution, even before the line that led to the earth's multicellular organisms divided into plants and animals. The work also shows the importance of comparative studies across different species to enhance our understanding of how fundamental mechanisms function at the cellular level in both the plant and animal kingdoms, and by extension in humans.

Reading Questions: Article 3

  1. Why is immune response from plants necessarily different from that of animals?
  2. Describe the ‘regulatory circuit’ that researchers characterized for BAK1.
  3. What is FLS2? What does FLS2 sense?
  4. How do plants ‘switch off’ their immune response? What do the plant’s enzymes add to the FLS2 receptors in order to deactivate and degrade them?
  5. What broader application does understanding the pathway have?

Plants Teach Humans a Thing or Two About Fighting Diseases

June 17, 2011 — Avoiding germs to prevent sickness is commonplace for people. Wash hands often. Sneeze into your elbow. Those are among the tips humans learn.But plants, which are also vulnerable to pathogens, have to fend it alone. They grow where planted, in an environment teeming with microbes and other substances ready to attack, scientists note.

Now, researchers are learning from plants' immune response new information that could help them understand more about humans' ability to ward off sickness and avoid autoimmune diseases.

In the latest issue of the journal Science, Texas AgriLife Research scientists report their findings of a "unique regulatory circuit" that controls how a plant turns on and off its immune sensor.

"Plants and animals live out their lives mostly in good health, though they may have been subjected to a lot of pathogenic microbes," said Dr. Libo Shan, AgriLife Research plant molecular biologist and lead author for the journal article. "Scientists all around the world have been interested in how a healthy host can fend off invasions of pathogens and turn off the defense responses promptly once the intruder risk factors are decreasing."

The research team found a "unique regulatory circuit" in which BAK1, a protein involved with cell death control and growth hormone regulation, recruits two enzymes -- PUB12 and PUB13 -- to the immune sensory complex and fine-tunes immune responses.Basically, the surface of plant cells has sensors that sense microbial invasion.

One of the best-understood plant receptors is FLS2, found in the common laboratory plant Arabidopsis.FLS2 could sense the bacterial flagellin, which is a part of the flagellum, or tail-like projection on cells that help them to move. When FLS2 perceives flagellin, a series of "evolutionary conserved immune responses" is activated to fend off bacterial attack, Shan said.

But the immune response cannot stay activated or the plant will stop growing and producing."To avoid detrimental effects of long-lasting immune activation, plant and animal hosts need a way to switch the activation off," she noted. "How that can be has been a mystery to scientists."

The team discovered that the flagellin perception recruited PUB12 and PUB13 to the receptor FLS2 complex.Those two enzymes could add a biochemical signature tag, ubiquitin, to the FLS2 receptors that inform cells to degrade the immune sensors, she added.As a result of these actions, immune signaling decreased.

Knowing how immune signaling works may help researchers devise ways to help plants and animals -- including humans -- regulate their immune systems.

Shan said the mechanism her lab discovered is very broad in that it can be found in both plants and animals."We needed to understand the mechanism so that we can regulate it better," she said. "The host needs to know when the signal is triggered (to fight off a pathogen). Then the immune response needs to go quickly up and then back down when it is no longer needed."Shan believes that this ability could lead to cures, rather than medical relief, from an assortment of ailments including allergies and autoimmune diseases.

"Plants have figured out how to survive in terms of disease and pest resistance," she added. "And what we learn from them at the molecular level might help us understand animal pathogens better."

Reading Questions: Article 4

  1. What is the difference in response between the tomato and Arabidopsis plants to bacteria?
  2. What are N-glycans? What is their normal role in the cell?
  3. What did researchers find when they mutated various N-glycans? Why is pathogen recognition important in an organism’s response to infection?
  4. How can knowledge of how an organism is resistant to a disease be applied in preventing disease in susceptible organisms?

Plant's Ability to Identify, Block Invading Bacteria Examined

This is a flower of the Arabidopsis thaliana plant. (Credit: (USDA-Agriculture Research Service photo by Peggy Greb).)

Mar. 21, 2010 — Understanding how plants defend themselves from bacterial infections may help researchers understand how people and other animals could be better protected from such pathogens.

That's the idea behind a study to observe a specific bacteria that infects tomatoes but normally does not bother the common laboratory plant arabidopsis. Researchers hoped to understand how infection is selective in various organisms, according to a Texas AgriLife Research scientist.

Dr. HisashiKoiwa collaborated with colleagues in Germany and Switzerland to examine the immune capabilities of different mutations of the arabidopsis plant. Their findings appeared in the Journal of Biological Chemistry.In this study, the team was trying to figure out how a plant defends itself rather than how it gets sick, said Koiwa, who provided about 10 different lines of mutant arabidopsis plants grown in his lab at Texas A&M University."By learning what is wrong with a sick plant," he said, "we can study how a plant can defend itself, what mechanisms it uses for protection."

The team had to examine the plants at the cellular level where molecules are busy performing different jobs.To understand the process, one has to examine components such as "N-glycans, receptors and ligands," Koiwa said.The N-glycan is a polysaccharide that is critical in protein folding, a natural process which if it becomes unstable leads to various diseases, Koiwa explained. A receptor is a protein decorated with N-glycans, which awaits signals from the ligands that bind and activate receptor molecules.

In viewing this mechanism across various arabidopsis plants that had been mutated to achieve different N-glycan structures, the researchers found one particular N-glycan that was critical in making sure that the receptor molecules can recognize the targeted bacteria molecule, he said.If that polysaccharide can recognize a pathogen, it can prevent infection thus making the plant immune to that disease, the scientists noted.

"The question is fundamental. Why are we healthy in an environment of so many different bacteria?" Koiwa asked. "Why can one pathogen infect one kind of organism and not others? In this case, the same bacteria normally infects tomato plants but not arabidopsis."

Koiwa said many researchers are studying the pathway, or molecular road, that a pathogen takes on its journey to infect another organism. They want to find what "gates" exist in an organism that prevent infection with the notion that the same blocks could be adapted in a susceptible organism to prevent disease.

He said eventually using this pathway to develop new plant varieties that do not allow pathogens inside the cells would be better than breeding lines that are merely "resistant" to diseases.

"In the case of resistance, a plant has to try to fend off an infection that has been let in," Koiwa explained. "But a properly working immunity system does not let the pathogen in, so the plant does not get sick in the first place."