• Nilgun Tumer
  • Nilgun Tumer
  • Distinguished Professor
  • Department: Department of Plant Pathology
  • Program(s): Microbiology and Molecular Genetics Graduate Program
  • Phone: 1.8489326359
  • Rutgers University
  • School of Environmental & Biological Sciences
  • 208B Foran Hall
  • 59 Dudley Road
  • New Brunswick, NJ 08901-8520
  • Key Words: 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). Ricin 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. Ricin is used in targeted killing of cancer cells and is a concern for bioterrorism. The related Shiga toxins (Stxs) produced by Shigella and E. coli O157:H7 (STEC) cause food-borne outbreaks and are major concerns for public health. Currently, there are no vaccines or therapeutics to protect against ricin or Stx producing E. coli. Our lab pioneered yeast as a powerful model to study the mode of action of RIPs. We developed surface plasmon resonance (SPR) methods with a Biacore to investigate the direct interactions of ricin and Shiga toxins with ribosomes and using these methods we established that ricin and Shiga toxins bind to the ribosomal P stalk to depurinate the SRL. Our work showed for the first time that ribosome binding site of ricin A chain (RTA) is on the opposite face of the active site and provided evidence that binding to P stalk stimulates the catalytic activity of RTA by reorienting its active site towards the SRL. We identified the key residues in RTA and the A1 subunits of Stxs critical for binding ribosomes and showed that toxicity can be reduced by inhibiting toxin interactions with the ribosome.

We showed that peptides mimicking the P protein binding site inhibit the depurination activity of RTA by binding to the ribosome binding site and disrupting the interaction of RTA with the P stalk without targeting the active site. These studies established toxin-ribosome interactions as a new target for inhibitor discovery. We have set up fragment screening using Biacore T200 and identified fragments that bind to RTA and to the A1 subunits of Stxs and inhibit their activity. These innovative approaches have culminated in peptides and fragments that bind to the toxins and show dose-dependent inhibition of their activity.

We study the mode of action of trichothecene mycotoxins produced by Fusarium graminearum, which causes Fusarium head blight (FHB), a devastating disease affecting cereal crops. There is no effective resistance to FHB in wheat or barley. Using chemical genomics approaches we identified mitochondria as a target of trichothecene mycotoxins and showed that trichothecene-induced mitochondrial oxidative stress plays a major role in trichothecene toxicity. We screened activation tagged Arabidopsis lines for resistance to trichothecenes and identified a novel lipid transfer protein (LTP) that confers resistance to FHB and trichothecene mycotoxins in transgenic plants.

Dr. Tumer directs the Core Facility at the School of Environmental and Biological Sciences (SEBS), which provides a wide array of services to Rutgers community.