Heme is a key and essential compound for the vast majority of living organisms. Heme, as a cofactor in a variety of proteins, is widely acknowledged to be essential for gas transport, respiration, xenobiotic detoxification, peroxide production and destruction, fatty acid desaturation, and a variety of one electron transfer reactions. Over the past decade the number of roles identified for heme has grown substantially. It has become clear that heme is also an important intracellular regulatory ligand. Among the list of biological processes for which higher eucaryotic heme-binding proteins have now been implicated is regulation of circadian rhythm, adipogenesis, glucose homeostasis, microRNA processing, gas sensing, control of ion channels, and intra- and intercellular signal transduction. The list of bacterial heme-binding sensors seems to grow with each new journal publication, and the role of the heme-containing DevS-DevR proteins of Mycobacterium tuberculosis as regulators of passage into the dormant stage has attracted considerable attention for obvious biomedical reasons. Dietary heme also serves as a significant source of iron for many organisms including pathogenic bacteria. A search of PubMed for “heme” yields over 2500 listed publications in the past year.
The Dailey lab’s research focuses on the enzymes responsible for heme biosynthesis. Current studies involve structure/function investigations of the terminal enzymes of heme biosynthesis and their relationship to the human genetic diseases known as porphyrias, biochemical characterization of the enzymes from both eukaryotic and prokaryotic organisms, identification and characterization of novel and previously unidentified genes involved in heme synthesis and transport, protein-protein interactions among heme synthesis enzymes, and regulation of expression and translocation of heme synthetic enzymes.