Structure-Function of RNAs and Proteins
Professor Pardi's primary research interests are in the area of biophysical chemistry and NMR spectroscopy. High-resolution multi-dimensional NMR experiments are used to probe the structure and dynamics of biomolecules in solution. The Pardi group also continues to develop improved methods for determining the solution structures of proteins and RNAs. A long-range goal is to understand the relationship between the structures (and dynamics) of these molecules and their biological functions.
Systems currently being studied in the lab include the hammerhead self-cleaving catalytic and a therapeutic RNA aptamer, Macugen, that binds with extremely high affinity to the angiogenic regulatory protein VEGF.Ìý This aptamer is currently used in the treatment of age-related macular degeneration. Structural and biochemical studies are being performed on other RNA and DNA aptamers that bind with high affinity and specificity to the angiogenic regulatory protein VEGF. ÌýThe goal here is to better understand the molecular mechanism by which these aptamers recognized their target protein with such high affinity and specificity. ÌýA variety of biophysical methods are used to probe the structure and dynamics of RNAs and proteins.Ìý For example ensemble and single molecule fluorescence resonance energy transfer techniques are being used to follow global folding of the hammerhead ribozyme, to better understand the catalytic mechanism of this ribozyme.
We also have collaborations with several other groups in the Department.Ìý For example, NMR is being used to study the structures of proteins involved in assembly of the outer membranes in gram-negative bacteria with Professor Sousas's group. Studies of protein dynamics are being used to help design brighter and more photostable red fluorescent proteins in collaboration with Professors Palmer and R. Jimenez and in collaboration with Professor Ahn, NMR spectroscopy is being used to understand how protein dynamics affect the catalytic activity of the MAP kinase, ERK2.