n the in-cites interview below, Dr. Gregory Martin of Cornell University comments on his paper "Map-based cloning of a protein kinase gene conferring disease resistance in tomato," (Science 262: 1432-6, 26 November 1993). This paper is currently the third most-cited paper in the field of Plant & Animal Sciences in the ISI Essential Science Indicators Web product, with 586 total cites to date. Dr. Martin’s record in this field includes 57 papers cited a total of 1,602 times to date. Dr. Martin is a Scientist at the Boyce Thompson Institute for Plant Research and Professor of Plant Pathology at Cornell.

...a lot of progress has been made by many labs over the past 10 years we are still lacking answers to some of the key questions...

Plant disease resistance genes are of great economic importance but they are also the linchpin for some very interesting biology involving the communication that occurs between two organisms (i.e., the plant and the pathogen). The genetic mechanism specifying resistance to bacterial speck disease in tomato is typical of the "gene-for-gene" type of disease resistance that likely occurs in all plant species. In gene-for-gene interactions, a plant R protein (e.g., Pto) is able to specifically recognize the expression of a pathogen protein (e.g., AvrPto). This specific recognition activates signaling pathways in the plant that result in a variety of defense responses which ultimately inhibit growth of the pathogen. The cloning of Pto provided some first insights into the molecular basis of a recognition event underlying a gene-for-gene interaction and also provided a tool (the gene) that could be exploited to learn more about recognition and signal transduction underlying plant immunity.

Pto encodes a protein kinase, and that immediately suggested it played a role in phosphorylating other proteins as part of a signaling pathway activating defense responses. It was unexpected that Pto was an intracellular protein, and that observation raised the question of how Pto could recognize the presence of the pathogen effector protein (AvrPto) that was expressed within the bacterial cell. Later work from many labs revealed that many bacterial pathogens inject their effector proteins directly into the plant cell via a type III secretion system. Thus it turns out that recognition of pathogen proteins often occurs inside of the plant cell. Another interesting finding was that Pto is a member of a gene family consisting of five related genes all clustered within about 40 kilobases on chromosome 5. This observation was consistent with much previous plant breeding research that indicated many R genes occur within small genetic intervals. The clustering of R genes suggested that recombination events might occur among them giving rise to new resistance specificities. Although this doesn’t appear to have happened in the Pto region there is evidence in other R gene clusters that intergenic recombination has occurred.

   Where has this research gone since the publication of your paper? Where do you see it going 10 years from now?

I’ve just written a review chapter about this topic and it’s hard to summarize in a few words! Since the cloning of the Pto gene I have focused all my research efforts on understanding how the kinase it encodes plays a role in recognition of the AvrPto effector protein and how it activates signaling pathways to induce defense response. Although there is a long way to go before we really understand the full complexity of this system we have learned several important things in the past 10 years. First, we and others found that Pto and AvrPto physically interact in the plant cell. The interaction is very specific and mutations in either protein that disrupt the interaction also lead to loss of disease resistance. Second, several proteins have been identified that appear to play a role in signal transduction after the recognition event. These proteins include Prf which contains a region of leucine-rich repeats and a putative nucleotide binding site. Many other R genes encode proteins with similarities to Prf and so this discovery has raised the possibility that Pto-like kinases might participate in other R gene pathways.

Other proteins that act downstream of Pto include another serine/threonine protein kinase, and a family of transcription factors (ERFs). Finally, we have recently performed a comprehensive expression profiling of the Pto-mediated defense response and identified over 400 genes whose expression changes in the tomato leaf in the first four hours after bacterial infection. I encourage anyone who would like to learn more about this system to look at a recent review chapter on the Pto pathway that I’ve written with my postdoc Kerry Pedley (Pedley and Martin, "Molecular basis of Pto-mediated resistance to bacterial speck disease in tomato," Annual Review of Phytopathology, 2003 [available as a Review Online]).

   What lessons would you draw from your work to share with the next generation of researchers?

The molecular basis of disease resistance (and susceptibility) is complex, and although a lot of progress has been made by many labs over the past 10 years we are still lacking answers to some of the key questions (for example, we don’t know the complete set of proteins that are involved in the recognition event and we don’t understand how this recognition complex activates defense signaling). The study of plant-pathogen interactions continues to be an exciting field for basic research and it also offers the opportunity of developing some solutions for serious disease problems in the field. In fact, for me, one of the challenges for the future is to figure out how we can exploit our understanding of the molecular mechanisms underlying resistance in order to develop plants that are less disease-prone and which require fewer pesticides.

Gregory B. Martin, Ph.D.
Cornell University and the Boyce Thompson Institute for Plant Research
Ithaca, NY, USA