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This application is for partial support of a FASEB Summer Research Conference on Trace Element Metabolism: From Model Organisms to Humans, to be held at Snowmass, Colorado June 15-20, 2008. This meeting will be the 10th in this series. Trace elements are of vital importance in agriculture, medicine and the inter-relationship between agriculture and human health. This proposed FASEB Summer Research Conference will focus on topics covering the most exciting and important breakthroughs in understanding both basic and applied aspects of trace element homeostasis and metabolism. In this meeting we will largely focus on the trace elements iron (Fe), copper (Cu), zinc (Zn), selenium (Se) and boron (B), as they constitute a group of trace elements that serve critical roles in biology. As is evidenced by the dramatic increase in the number of newly discovered biological processes in which trace elements play pivotal roles as catalysts, sensors, regulatory molecules and structural co-factors, this field of investigation is expanding at an extremely rapid pace. Furthermore, the number of independent research groups in this field, spawned from trainees derived from established laboratories in the field, as well as investigators from distinct disciplines who have moved into this field, is also growing at break-neck speed. Given the importance of the field and its potential to continue to make ground-breaking discoveries of broad fundamental importance and the large scientific demand for opportunities to communicate and interact, the topic of this meeting is both exciting and timely. <P>
The specific aims for this proposal are as follows: <OL> <LI> To organize and support a meeting on the latest scientific advances in the research area of trace element homeostasis and metabolism. This conference will be held June 15-20, 2008 in Snowmass, Colorado. The conference will primarily focus on discussions of research related to Fe, Cu, Se, Zn and B, but additional areas for presentation and discussion are welcome. <LI>This meeting aims to promote interactions between scientists and clinician/scientists to share new discoveries in the field of trace element metabolism as it relates to normal growth, development and nutrition and to enhance new collaborations that will move the field forward. <LI>To directly involve newly independent scientists and trainees including graduate students and postdoctoral fellows, women, minorities and the disabled in the conference. Our goal is to provide access to cutting edge science via oral and poster presentations, to allow opportunities for conversations with established investigators and other colleagues and to encourage and support long-term and significant involvement in this important area of biomedical research.
NON-TECHNICAL SUMMARY: Trace metals such as Cu, Fe, Se, Zn and B serve essential roles as catalytic or structural co-factors in biochemistry for virtually all life forms on this planet. Metals such as Cu and Fe serve as redox active co-factors for a wide variety of enzymes involved in biochemical processes such as oxidative phosphorylation, photosynthesis, protection from oxidative stress, DNA synthesis and repair, regulatory responses to hypoxia, pigmentation, neurotransmitter biogenesis and neuropeptides maturation, chromatin modification, oxygen binding, connective tissue maturation and a host of additional processes critical to life. Zn serves both as a catalytic co-factor and as a pivotal structural component of Zn finger proteins, hundreds of which are expressed in the typical eukaryotic cell. Mutations in plants and animals are known to underlie abnormal growth and development and therefore have severe consequences for the overall quality of life on this planet. Through recent advances in basic research, many human diseases of micronutrient-trace element excess or deficiency have been well characterized at the level of their molecular mechanisms and the associated defect. For example, combined genetic, biochemical, cell and molecular biology approaches in the mid-1990s allowed the identification of mutations in the ATP7A P-type Cu-transporting ATPase responsible for Menkes Disease, an early postnatal lethal disease of Cu absorption. Similar studies succeeded in the identification of genes responsible for Wilson's Disease (hepatic Cu hyperaccumulation), hereditary hemachromatosis (Fe overload), Friedrich's Ataxia (mitochondrial Fe maldistribution), aceruloplasminemia (Fe distribution defect associated with neuropathy), acrodermatitis enteropathica (Zn absorption defect) and transient neonatal Zn deficiency (defect in Zn secretion into milk in the mammary gland). Additional basic science studies have shown the essentiality of Zn and Cu importers for embryonic development and intracellular Cu chaperone proteins for neonatal success. More recently, associations between changes in the accumulation of Fe and Cu and neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, in prion disease and the role of Cu, Zn superoxide dismutase maturation in Familial Amyotropic Lateral Sclerosis (Lou Gehrig's Disease) have been reported. Previous advances in this area of medicine would not have been possible without these fundamental advances in understanding the underlying mechanisms of trace element homeostasis. Such understanding of trace element homeostasis is key to ultimately developing a sound scientific basis for dietary recommendations, for developing novel nutritional supplements with enhanced absorbance and distribution profiles, and for developing diagnostic markers and tests for human dietary deficiencies or genetic diseases of trace element balance.
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APPROACH: Trace metals such as Cu, Fe, Se, Zn and B serve essential roles as catalytic or structural co-factors in biochemistry for virtually all life forms on this planet. Metals such as Cu and Fe serve as redox active co-factors for a wide variety of enzymes involved in biochemical processes such as oxidative phosphorylation, photosynthesis, protection from oxidative stress, DNA synthesis and repair, regulatory responses to hypoxia, pigmentation, neurotransmitter biogenesis and neuropeptides maturation, chromatin modification, oxygen binding, connective tissue maturation and a host of additional processes critical to life. Zn serves both as a catalytic co-factor and as a pivotal structural component of Zn finger proteins, hundreds of which are expressed in the typical eukaryotic cell. Mutations in plants and animals are known to underlie abnormal growth and development and therefore have severe consequences for the overall quality of life on this planet. Through recent advances in basic research, many human diseases of micronutrient-trace element excess or deficiency have been well characterized at the level of their molecular mechanisms and the associated defect. For example, combined genetic, biochemical, cell and molecular biology approaches in the mid-1990s allowed the identification of mutations in the ATP7A P-type Cu-transporting ATPase responsible for Menkes Disease, an early postnatal lethal disease of Cu absorption. Similar studies succeeded in the identification of genes responsible for Wilsons Disease (hepatic Cu hyperaccumulation), hereditary hemachromatosis (Fe overload), Friedrichs Ataxia (mitochondrial Fe maldistribution), aceruloplasminemia (Fe distribution defect associated with neuropathy), acrodermatitis enteropathica (Zn absorption defect) and transient neonatal Zn deficiency (defect in Zn secretion into milk in the mammary gland). Additional basic science studies have shown the essentiality of Zn and Cu importers for embryonic development and intracellular Cu chaperone proteins for neonatal success. More recently, associations between changes in the accumulation of Fe and Cu and neurodegenerative diseases such as Parkinsons and Alzheimers diseases, in prion disease and the role of Cu, Zn superoxide dismutase maturation in Familial Amyotropic Lateral Sclerosis (Lou Gehrigs Disease) have been reported. Previous advances in this area of medicine would not have been possible without these fundamental advances in understanding the underlying mechanisms of trace element homeostasis. Such understanding of trace element homeostasis is key to ultimately developing a sound scientific basis for dietary recommendations, for developing novel nutritional supplements with enhanced absorbance and distribution profiles, and for developing diagnostic markers and tests for human dietary deficiencies or genetic diseases of trace element balance.