Our research focuses in two main areas: 1.) The study of the biology of selenium as a biological catalyst especially in the model organism Clostridioides difficile. 2.) The study of the properties and application of cerium oxide-based nanomaterials

The role of selenoenzymes in pathogenic microbes. We are elucidating the role of Stickland reactions in the energy metabolism and toxin regulation of the nosocomial pathogen Clostridioides difficile. Our underlying hypothesis: Growth of this and related anaerobes (C. botulinum, C. sporogenes, C. sticklandii, Treponema denticola) is dependent on the presence of the selenium-dependent oxidoreductases glycine reductase and/or D-proline reductase for optimal growth in the host. We are currently elucidating phenotypes from C. difficile mutants that lack one or more of these selenoenzymes. We also are studying the use of selenium as a catalyst in a group of enzymes known as selenium-dependent molybdenum hydroxylases (SDMH), also in C. difficile.

Developing applications for cerium oxide- based nanomaterials. Cerium oxide nanoparticles (nanoceria) have been shown to reduce oxidative and nitrosative stress in large number of studies using both cell culture and animal models. We have discovered that these nanoparticles can effectively act as superoxide dismutase and catalase mimetics. We have also observed nitric oxide radical scavenging and recently shown that these nanoparticles can accelerate the decay of the harmful oxidant peroxynitrite. In collaboration with Dr. Sudipta Seal, we are continuing to study the anti-inflammatory properties of this material and beginning to development various biomaterials using these interesting rare earth oxides.

Representative and Recent Publications

  1. Michael Johnstone, Anshupriya Si, Alexander Landgraf, Steven Sucheck and William Self (2022) Evaluation of Derivatives of (+)-Puupehenone against Clostridioides difficile and Other Gram-Positive Bacteria ACS Omega Sep 9;7(37):33511-33517.
  1. Michael Johnstone and William Self (2022) D-Proline reductase underlies proline-dependent growth of Clostridioides difficile J. Bacteriol. Aug 16;204(8):e0022922.
  1. Michael A. Johnstone, Samantha J. Nelson, Christine O’Leary, and William T. Self (2021) Exploring the selenium-over-sulfur substrate specificity and kinetics of a bacterial selenocysteine lyase.  Biochimie, Volume 182, March 2021, Pages 166-176.
  1. Zhongxin Ma, Kyle T. Strickland, Michelle D. Cherne, Esha Sehanobish, Kyle H. Rohde, William T. Self and Victor L. Davidson (2018) The Rv2633c protein of Mycobacterium tuberculosis is a non-heme di-iron catalase with a possible role in defenses against oxidative stress. Biol. Chem. 293: 1590-1595. 
  1. Kathleen McAllister, Laurent Bouillaut, Jennifer Kahn, William Self, and Joseph Sorg (2017) Using CRISPR-Cas9-mediated genome editing to generate difficile mutants defective in selenoproteins synthesis Scientific Reports 7, Article number: 14672 

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