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2024 Ruth Allen Award: Timothy Friesen​

Timothy L. Friesen was born in Madelia, MN, and received a B.S. degree in biology from Minnesota State University, Mankato (1992) and a Ph.D. degree in plant pathology from North Dakota State University (2001) under Dr. Jack Rasmussen. He worked as a postdoc in the Sugar Beet and Potato Research Unit of USDA-ARS from 2001 to 2002 in the lab of Dr. John Weiland. In 2002, Dr. Friesen joined ARS permanently as a research plant pathologist in the Cereal Crops Research Unit of the Northern Crop Science Laboratory in Fargo, ND, and as an adjunct faculty member in the Department of Plant Pathology at North Dakota State University. 

When Dr. Friesen began his research program in 2002, little was known about the molecular basis of the host-pathogen interaction between the causal organisms of septoria nodorum blotch (SNB; Parastagonospora nodorum) and wheat. Although it was speculated that host-selective toxins (necrotrophic effectors) produced by P. nodorum were important in the disease, the specifics were unknown, and no relevant genes in the pathogen or the host had been characterized. Friesen's research changed this situation dramatically—first by demonstrating necrotrophic effectors as the primary determinants of disease, followed by the identification of the interacting host genes. Unlike the classical gene-for-gene interaction paradigm first proposed by H. H. Flor, where specific dominant avirulence factors produced by the pathogen are recognized by the corresponding dominant resistance gene products in the host, the necrotrophic interactions uncovered by Friesen act in an opposite manner, where proteinaceous necrotrophic effectors produced by the pathogens target dominant susceptibility genes/pathways in the host, leading to disease. Friesen's research team referred to this as an inverse gene-for-gene interaction, which has now been shown to occur in several important necrotrophic pathogen-host interactions. 

Fleshing out the inverse gene-for-gene hypothesis required cloning of the interacting gene pairs from the host and pathogen sides. Friesen and colleagues initially used classical genetics approaches, followed by other approaches as they became available, to identify and functionally characterize both the pathogen and host components. By focusing on a single interaction at a time, the pathogen and host mechanisms were elucidated, providing a more complete understanding of how the pathogen manipulates the host defense machinery to complete its life cycle. 

SnToxA was the first proteinaceous necrotrophic effector gene identified in P. nodorum, a gene/protein previously identified in Pyrenophora tritici-repentis. Friesen and colleagues showed that this gene had been transferred horizontally from P. nodorum to the tan spot fungus Pyrenophora tritici-repentis. In collaboration with colleagues, the wheat susceptibility gene (Tsn1) targeted by both PtrToxA and SnToxA was cloned and shown to be a unique, but classical-looking, resistance gene that confers susceptibility rather than resistance. Tsn1 is now known to be targeted by three wheat pathogens harboring ToxA, validating this inverse gene-for-gene model in multiple systems. This work led to breeding approaches to remove Tsn1 from commercial wheat cultivars to enhance resistance to three different pathogens. 

Another effector named SnTox3 was cloned in 2009, which provided the necessary tools for cloning the host susceptibility gene Snn3-D1. Additional work revealed the mechanisms of the interactions between these genes and showed that SnTox3 targeted multiple host susceptibility genes. This work was followed by cloning and functional characterization of the necrotrophic effector SnTox1 in 2012. SnTox1 was shown to not only target the wheat susceptibility gene Snn1, but also to have a chitin-binding function that protects the pathogen from wheat-produced chitinase degradation during colonization. Snn1, the host susceptibility target, was subsequently cloned in 2016 and was shown to be a wall-associated kinase, a classical contributor to host surveillance of invasion that, like other inverse gene-for-gene interactions, results in susceptibility rather than resistance. The Snn6-SnTox6 and Snn7-SnTox7 interactions were identified in 2015. Subsequent work on the SnTox2-Snn2, SnTox6-Snn6, and SnTox7-Snn7 interactions showed that a single proteinaceous necrotrophic effector, renamed SnTox267, targeted the Snn2, Snn6, and Snn7 pathways, respectively. In total, Friesen and colleagues cloned and characterized five necrotrophic effectors and three host susceptibility genes. Friesen also has demonstrated that an inverse gene-for-gene interaction occurs within net blotch of barley. Friesen's groundbreaking research on the interaction between multiple fungal necrotrophic effectors and susceptibility proteins in their hosts has greatly increased our understanding of necrotrophic pathogen biology and evolution and the mechanism of host resistance. His thorough analyses and cloning of both host and pathogen genes contributing to these interactions greatly improved our understanding of inverse gene-for-gene systems that regulate the development of disease in cereal crops. This work has served as a paradigm shift that fundamentally altered our thinking on how necrotrophic specialist pathogens evolve to target their respective hosts. 

Friesen's work has also had practical implications for plant pathology. One of the most obvious was to identify susceptibility genes and eliminate them from wheat cultivars and breeding materials through marker-assisted selection and screening them using purified necrotrophic effectors. These approaches are now being used globally. While developing the tools to characterize these necrotrophic interactions, Friesen also became a leader in fungal genomics in both P. nodorum and P. teres. Collaborations with wheat geneticists and breeders have led to the corelease of 17 new wheat cultivars or improved germplasm lines. 

Friesen has published more than 150 peer-reviewed papers, collectively cited more than 11,700 times. His discoveries have led to more than 50 speaking invitations and 16 invited book chapters. He has served the scientific community as a mentor to graduate students and postdocs, with several going on to productive faculty, government, and industry careers. Friesen has been an external examiner for Ph.D. projects of six international graduate students and has served as a member of organizing committees for several international meetings. Friesen has served as a member of the APS Office of Public Relations and Outreach Board (2016–2021) and has been associate editor, senior editor, and editor-in-chief for the APS journal Molecular Plant-Microbe Interactions. Friesen's outstanding scientific achievement leading to the elucidation of inverse gene-for-gene interactions involving necrotrophic fungal pathogens has fundamentally changed our understanding of host-pathogen interactions and resulted in practical tools for introgressing resistance into crops.