The Giedroc group is currently working in three separate areas united by their common use of the tools of biophysical chemistry, bioinorganic chemistry and structural biology to solve "nucleic acid-centric" problems in biological regulation. We have three major research efforts, all centered around understanding nucleic acid (DNA, RNA) structure and dynamics and interactions with regulatory proteins and ribonucleoprotein machines in the cell. A fourth project, the development of a heavy metal biosensing device, is a natural extension of one of these research interests.
We are a collaborative group and these projects provide both graduate and postdoctoral students with an opportunity to work at multidisciplinary interfaces in chemistry, biology and virology.
In this project, our goal is to understand the molecular mechanisms of how cells regulate the intracellular bioavailability of essential metals ions, notably Cu, Fe and Zn among others. This process, termed metal homeostasis and resistance, represents an important battleground in human host-bacterial pathogen interactions since these ions may be limiting or in excess, both detrimental to the survival of the invading microbe. Metal sensor proteins bind specific DNA sequences and regulate the expression of homeostasis genes in response to specific metal ions (more...).
In this project, we seek to understand the molecular mechanism of how elongating ribosomes are programmed to shift translational reading frames upon encountering a "frameshift" signal embedded in a messenger RNA. Many infectious RNA virus families, including retroviruses (HIV-1) and coronaviruses (the causative agent of SARS), employ this strategy to properly express their genomes. The frameshift signal is often an RNA folding motif called an RNA pseudoknot, and has become a important antiviral target (more...).
In this new collaborative project with JL Leibowitz's group at Texas A&M, we are employing biophysical chemistry and NMR spectroscopy to understand the structure and biological function of the very "tips" of the coronavirus genome, the 5' and 3' untranslated regions (UTRs) that direct the replication and propagation of SARS-CoV and closely related group 2 CoVs. We anticipate using mass spectrometry-based fingerprinting methods to identity cellular or virally encoded proteins that interact with specific RNA targets and NMR spectroscopy to solve their structures (more...).
