Source: Wageninen University, Newsletter Plant Sciences Group June 2009

As part of his doctoral research at the University of Amsterdam, PSG scientist Wladimir Tameling discovered a ‘main switch’ in the immune system of plants and animals. With a prestigious publication in Science (8 May, 2009) Tameling and his UvA supervisor Frank Takken are seeing that this research is having international impact. “The molecular switch we discovered is probably billions of years old,” says Tameling, scientist at the Plant Sciences Group of Wageningen UR. “It is present in both plants and animals and thus in humans too. The genetic genealogy tells us that it must have been present in a common ancestor of both plants and animals. There are even clues that at some point the DNA that codes for this protein domain jumped over (horizontally as it were) from bacteria to this common ancestor.” 

Despite its great age, the piece of protein’s function appears to be essential. “The switch plays a central role in the battle between an organism and its attackers,” Tameling explains. “When a bacteria, virus or fungus attacks, the organism’s immune system first has to deploy immune receptors to identify the attacker as a stranger. These receptors have so-called domains and ‘our’ switch is one of these domains. In addition to this domain, the receptors have another one that identifies the attacker. Our switch enters the stage as soon as the attacker is detected. After the pathogen is identified the switch is turned ‘on’, activating a whole cascade of signals that stimulate the immune reaction and neutralise the attacker.”

According to Tameling a plant attaches considerable importance to the on-and-off immune switch. “The switch that decides whether it lives or dies is activated by means of an ATP molecule, the cell’s energy carrier. This indicates that switching the immune system on and keeping it activated costs energy. If plants would do that continuously, even in moments when there are no attackers, massive amounts of energy would be lost that were needed for growth. The result would be a puny plant wasting its energy fighting non-existent enemies.” 
 
Auto-immune diseases

The genes that code for immune receptors were discovered in plants in the 1990s. Although it immediately became clear that they form an important defence against pathogens, it was not yet understood how the central domain – the switch – worked. “Now that we know how the domain switches we also have an increased understanding of the fundamental operation of the immune system in plants and animals,” Tameling continues. “It is fair to say that many scientists around the world have dived into these immune receptors. In plants these receptors are located in nearly all cells. In animals, and thus humans, they are especially present in the specific cells of the immune system and in the epithelium of the bowel.  Medicine is also extremely interested in their exact functioning as it has been discovered that a badly functioning immune receptor in humans and animals causes auto-immune diseases. People with Crohn’s disease, for instance, also suffer from an immune system that is ‘turned on’ when it shouldn’t be.”

After his doctoral research in Amsterdam and a postdoc in the UK, Tameling is continuing his research into the cascade of signals that starts in a cell once the switch is turned on. This work is being carried out in Wageningen within Matthieu Joosten’s group in the Laboratory of Phytopathology. “Supported by a veni grant from the Netherlands Organisation for Scientific Research (NWO), I am studying which proteins play a part in the cascade and how. With microscopic research I hope to discover exactly where they carry out their work too. For instance, the Rx protein is an immune receptor involved in the defence against potato virus X. The receptor appears to do ‘something’ in the nucleus of the plant cell. What, why and how it gets to the nucleus is something I hope to uncover.” 

Although Tameling is mainly interested in a fundamental understanding of the immune system, he recognises that his work may result in practical applications in due course. “Plant breeders have been using immune receptors for many years without knowing exactly how they work and which proteins they are. They just select those varieties that show a better defence against certain diseases. Now that we have come closer to understanding which proteins hide behind the immune reactions, breeding can become more specific. For example, we recently discovered another protein that strongly resembles an immune receptor, NRC1, and that appears to play a central role in the plant’s defence. Together with the company KeyGene we are currently researching whether that specific protein could be a useful target for breeders.”