Donald L. Nuss was born in Murfreesboro, TN. He received his B.S. degree in biology from Edinboro University of Pennsylvania in 1969 and his Ph.D. degree in biochemistry from the University of New Hampshire in 1973. He then joined the newly formed Roche Institute for Molecular Biology in Nutley, NJ, as a post-doctoral fellow and post-doctoral research associate before joining the Center for Laboratories and Research at the New York State Department of Health in Albany. In 1985, he returned to the Roche Institute as an associate and then full member (equivalent of professor), and he remained there until the closing of the institute in 1995. Upon leaving the Roche Institute, Nuss became director of the Center for Agricultural Biotechnology (currently the Center for Biosystems Research) and professor at the University of Maryland Biotechnology Institute, where he remains today.
The initial contributions made by Nuss to the field of plant pathology as a younger scientist included his revival and extension of Lindsay Black’s ground-breaking research on the dicot plant-infecting reovirus, Wound tumor virus. His truly transformative research in plant pathology, however, has been his work on the chestnut blight fungus, Cryphonectria parasitica, and associated virulence-attenuating hypoviruses. The work from Nuss and his laboratory colleagues has been the primary reason the fungus associated with this classic American pandemic has also become one of the most thoroughly understood of filamentous ascomycetes at the molecular level, one that informs our thinking of all other plant-pathogenic fungi and certainly the model system for studying fungus-virus interactions. More than 80 research papers on various aspects of C. parasitica/hypovirus biology have come from the Nuss lab, including two seminal papers in Science, seven in EMBO Journal, and 10 in PNAS, along with many, many others in the highest quality plant pathology, microbiology, and molecular biology journals.
During the early 1990s, the Nuss lab carried out and published studies that changed the way plant pathologists think about fungal viruses as biological control agents and as research tools. The first cloning, complete-sequence determination and elucidation of the basic genome expression strategy for a 12.7-kb dsRNA associated with hypovirulence of C. parasitica was reported by the Nuss laboratory in 1991. The viruslike genome organization and expression strategy of a hypovirulence-associated dsRNA was established, leading to the erection of the virus family Hypoviridae by the International Committee on Virus Taxonomy, the first virus family accepted by that organization whose members were devoid of a protein capsid. The cloning and sequencing of the first hypovirus-associated dsRNA was followed by the construction of a full-length infectious cDNA clone, the first reverse genetics system for any mycovirus. Hypovirus infection was initiated first by installing the hypovirus cDNA, under the control of a fungal gene promoter and terminator flanking elements, into the fungal host chromosome (transformation) and later by introduction of synthetic transcripts corresponding to the full-length hypovirus RNA into fungal spheroplasts (transfection). These major milestones demonstrated conclusively that a mycovirus was the causative agent of hypovirulence and provided the means for the genetic manipulation of mycoviruses for fundamental and applied applications. The hypovirus-bearing, transgenic C. parasitica isolates were used in trials conducted under the first USDA-APHIS permit for release of a genetically modified fungus. The results gained from release of transgenic hypovirulent C. parasitica have significantly informed decisions for release of other genetically modified fungi.
The transfection protocol was also used to establish hypovirus infections in a number of fungi related to C. parasitica that were not previously reported to harbor viruses, demonstrating that hypovirus host range and hypovirulence can be expanded to other pathogenic fungi. The transfection protocol has been used as a workhorse for subsequent molecular analysis of hypoviruses, including a number of ground-breaking studies on G protein-mediated signal transduction. A key role for G protein signaling has now been generally established for both phytopathogenic and medically important fungi. Chimeric hypoviruses constructed from infectious cDNA clones of mild and severe hypovirus strains allowed the mapping of specific regions of the hypovirus genome as contributing to differences in virus-mediated alterations in host phenotype, including colony growth morphology and canker morphology and spore production on chestnut stems. The ability to uncouple canker size from virus-mediated suppression of asexual sporulation is being investigated for the possibility of engineering more ecologically fit hypovirulent fungal strains.
The Nuss laboratory recently examined the role of RNA silencing in fungal antiviral defense and used the hypovirus/C. parasitica experimental system to 1) report the first experimental evidence that RNA silencing serves as an antiviral defense mechanism in fungi, 2) identify the first mycovirus-encoded suppressor of RNA silencing, 3) describe the first cloning and sequencing of mycovirus-derived small RNAs generated by RNA silencing, and 4) uncover the inducible nature of the RNA silencing pathway in response to virus infection. These finding were followed by the discovery of an unexpected role for RNA silencing in viral RNA recombination. The discovery that hypovirus DI RNA production and recombinant hypovirus vector instability requires an intact RNA silencing pathway has broad ramifications for understanding how new viruses emerge and for the development of better virus-based gene delivery systems.
Recently, Nuss has led the C. parasitica genome sequencing by the DOE Joint Genome Institute’s Community Sequencing Program. The Cryphonectria research community is in the process of manually annotating the assembled genome sequence, which will further enhance the utility of one of the few experimental systems with the capacity for efficiently manipulating the genomes of both eukaryotic viruses and their host. In summary, Nuss has taken chestnut blight research from the level of an interesting and well-studied American epidemic and developed a powerful experimental system capable of providing answers to some of the most fundamental questions in plant pathology and biology.
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