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Fedor Lab Personnel

Martha J Fedor

Martha J. Fedor, Ph.D.
Principal Investigator

mfedor@scripps.edu      

Fedor CV

Research in our laboratory focuses on RNA folding and catalysis with special interest in regulatory RNAs known as riboswitches. These RNA elements regulate bacterial gene expression in response to binding small ligands. We recently uncovered the first evidence of a new paradigm for RNA-mediated gene regulation when we found that the glmS riboswitch binds to an array of stimulatory and inhibitory glucose metabolites and integrates information about the overall metabolic state of the cell to control expression of the glmS gene. The glmS riboswitch response to multiple metabolites likely represents an early indication of a vast RNA-metabolite interactome that remains to be explored. The glmS riboswitch is also a ribozyme that mediates a self-cleavage reaction in which glucosamine-6-phosphate, its cognate metabolite, serves as a catalytic cofactor. We developed a novel method for determining nucleobase purine ionization states in the context of the fully functional riboswitch active site that helped us gain insight into role of the glucosamine-6-phosphate cofactor. Application of this method has allowed us to achieve a deeper understanding of the strategies used by all RNA enzymes to accomplish catalysis of biological reactions.
Dana Ruminski
Dana Ruminski, PhD
Postdoctoral Researcher
DRuminsk@scripps.edu
I am currently investigating the influence of RNA chaperone proteins on RNA folding pathways in vivo. We have previously demonstrated that in a cellular environment, the fate of unfolded, newly transcribed RNAs capable of forming competing structures is defined by a narrow threshold of thermodynamic stability. Above this threshold, thermodynamics govern folding, structures can be exchanged, and the most stable structures prevails. Below the threshold, the RNA is kinetically trapped in the structure that folds first. Even in physiological in vitro experiments, stable structures that form first dominate the folding outcome. Evidence suggests that RNA chaperones may be responsible for the structure exchange we observe in vivo by lowering free energy barriers for RNA unfolding and refolding. Using hairpin ribozyme cleavage activity as a direct indicator of changes in RNA folding, we are examining the affects of overexpression of RNA chaperone proteins on the threshold that determines the partitioning of competing structures.In the future, I hope to identify and characterize novel nucleotide-binding riboswitches. We recently demonstrated the ability of the glmS riboswitch to integrate signals from multiple hexose metabolites, leading to the new model that small-molecule-binding RNAs do not exclusively interact with a single, cognate ligand, but can sense and respond to several molecules. Our discovery of the ATP-sensing ydaO motif leads us to believe that nucleotide-sensing riboswitches may be abundant and responsive to a variety nucleotides and other ligands that allow the RNA to sense available energy in cells. Identification of these riboswitches could impact drug development for the many human diseases that arise from disruption of nucleotide signaling pathways.
Marisela Guaderrama
Marisela Guaderrama
Research Assistant
marisela@scripps.edu
I conduct experiments related to the lab's research, and also take care of general lab management and safety.
Courtney Curtis
Courtney Curtis
Administrative Assistant
CCurtis@scripps.edu
I provide administrative support for Dr. Fedor and laboratory personnel.