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The foundations of molecular biology are built from molecular structures. Seeing these structures helps unravel the mysteries of life and makes biochemistry exciting. X-ray crystallography has shown how DNA is copied; proteins are manufactured from basic metabolites and receptors receive signaling molecules and act to program new cell functions. Structural biology integrates chemistry and physiology. The Fletterick lab practices structural biology to learn about functions of systems of macromolecules in human biology and disease.
We study function of critical proteins with X-ray crystallography, mutagenesis, cell, biochemical and biophysical assays, and chemistry. A major molecular focus of our laboratory is structure-function analyses of nuclear receptors including those for thyroid hormone, and androgen, and for the less well characterized receptors called LRH-1, SF-1, SHP and DAX-1. All of these receptors respond to hormonal signals and control processes in metabolism, biosynthesis and development; LRH-1 is critical in stem cell function and the steroid receptors control many aspects of biology from behavior to cancer. We try to develop structure-function relationships that will teach us how to control these receptors and how these molecules control cell functions.
In related studies, we are learning how to form complexes of stem cell transcription factors and their partner proteins with nucleic acids. Protein DNA complexes have been made for about ten stem cell related transcription factor domains or full length proteins.