This application requests partial support for a meeting on Iron Sulfur Enzymes as part of a the Gordon Research Conference series to be held in Mount Holyoke College (South Hadley, MA) on June 10-15, 2012 with a broad and long-term goal of bringing together the world's leading experts in iron-sulfur clusters, focusing on enzymatic mechanisms, biogenesis, roles in regulation and in human disease in a uniquely cross-disciplinary manner. First organized in 1994 to focus on nitrogenase and its unique iron sulfur chemistry, knowledge about iron sulfur clusters has grown exponentially in the last two decades and, in 2006, the name of the conference was changed accordingly to Gordon Conference on Iron Sulfur Enzymes. The conference has tremendous breadth, featuring sessions on numerous iron sulfur enzymes of unicellular organisms, animals and plants, which provide important insights into how these versatile proteins are synthesized and utilized. Proteins containing iron-sulfur cofactors perform a variety of biological functions, ranging across electron transfer, acid- base catalysis, and sensing where they are agents for cell regulation through transcription (DNA) or translation (RNA). They are redox catalysts for radical-based reactions and the activation of H2, N2 and CO2, processes that offer scientific and economic challenges for industry. Iron-sulfur centers provide the focus for fundamental investigations of chemical bonding, spectroscopy, structure and molecular mechanism, and their functions have numerous implications for health, medicine and applications for technology, including renewable energy. The specific aim of this conference is to include distinguished speakers and discussion leaders from many fields, and topics will range from mechanistic discussions of bacterial enzymes to discussions of an emerging class of human diseases characterized by abnormalities in their iron-sulfur cluster biogenesis pathway. The health relatedness of the meeting is clear and will be discussed extensively. Three new diseases that result from mutations of genes in the iron-sulfur biogenesis pathway have been discovered since 2010, and there are no effective therapies for any of the diseases, including Friedreich ataxia, a disease characterized by progressive neurodegeneration and progressive heart failure. Novel therapeutic strategies are needed, and mixing the chemists and medical doctors together for the first time has the potential to catalyze progress in the field. PUBLIC HEALTH RELEVANCE: Iron sulfur cofactors are essential for virtually all forms of life, and much progress has been made on understanding their special chemical attributes and their unique contributions to metabolism. In the last ten years, it has become clear that failure to correctly synthesize iron sulfur clusters and proteins causes a range of rare and serious diseases, ranging from infantile lactic acidosis and seizures to Friedreich ataxia, a disease in which patients survive until early adulthood, and ISCU myopathy, in which patients have a normal lifespan, but have marked impairment of skeletal muscle function. The discussion of current research at this Gordon Research Conference will define important questions and problems that are associated with a growing list of unique diseases, and this is a crucial opportunity to bring researchers together to work on development of mechanistic insight into how iron-sulfur clusters are assembled and transferred, which may lead to new treatment strategies for diseases of iron sulfur cluster deficiency.