Department of Plant Pathology
208B Foran Hall
School of Environmental & Biological Sciences
59 Dudley Road
New Brunswick, NJ 08901-8520
Ribosome inactivating proteins, trichothecene mycotoxins, ribosome interactions, toxin mechanism of action, global responses to toxins
Our research focuses on the mechanism of action of ribosome inactivating proteins (RIPs) and trichothecene mycotoxins. Ricin and pokeweed antiviral protein (PAP) produced by plants and Shiga toxins produced by bacteria are RIPs, which depurinate the α-sarcin/ricin loop (SRL) of the large rRNA and inhibit protein synthesis. The Shiga toxin-producing Escherichia coli infections are associated with severe gastrointestinal disease in humans and are responsible for significant morbidity and mortality world-wide. There are no vaccines or therapeutics against ricin or Shiga toxin producing bacteria. We examine how toxins traffic to the ribosome, how they interact with ribosomes, inhibit translation and cause cell death. Our work has established the importance of the ribosomal stalk structure in facilitating the depurination activity and ribosome specificity of ricin and Shiga toxins in yeast and in human cells. We have identified the structural features of ricin critical for ribosome binding. We are using global approaches to identify cellular pathways that contribute to the toxicity of RIPs. We showed that RIPs inhibit the unfolded protein response (UPR) and inhibition of the UPR contributes to their toxicity. These results have provided new molecular leads for the development of RIP antidotes. Another project focuses on trichothecene mycotoxins, which function as virulence factors in the infection of cereals with Fusarium graminearum, the leading cause of Fusarium head blight (FHB). FHB significantly impacts yield, grain quality, and food safety due to the accumulation of toxic and heat stable trichothecene mycotoxins in food. In a genome-wide screen in yeast, we identified the mitochondria as an important target of trichothecene mycotoxins and showed that they inhibit mitochondrial translation and alter mitochondrial membrane morphology. Using activation tagging in Arabidopsis, we identified plant genes that confer resistance to trichothecenes. Our current research focuses on the role of these genes in resistance to trichothecene mycotoxins and FHB in wheat and barley.