Iron is an essential nutrient and the ability to accumulate iron from the diet is crucial for human health. Currently, more people suffer from malnutrition due to micronutrient deficiencies than from deficiencies of protein or energy and it is estimated that over 2 billion people worldwide suffer from iron deficiency. In agriculture, the availability of iron in soil plays a major part in determining crop yields. In addition, plants are the main dietary source of iron for much of the world's population. However, iron can also be toxic to both plants and animals when present at high levels. Thus, all cells must carefully regulate iron uptake. The long-range goal of these studies is to understand how plants take up iron from the soil and how plants maintain proper iron levels in the various cells/tissues of the plant. A combined genetic, molecular and biochemical approach will be used to address two major open questions regarding iron metabolism in plants. First, experiments will be conducted to elucidate the molecular mechanisms underlying iron transfer to mitochondria. Second, experiments will be conducted to decipher the mechanisms involved in plant iron deficiency signaling response pathways. The proposed studies will ultimately lead to a better understanding of iron uptake in plants and to the design of plants that are capable of growth on iron deficient soils and that accumulate iron and thus have a higher nutritional value. This collaborative project will provide unique mentoring opportunities. Because the Biology Dept at USC has a large number of minority students, the proposed research project has the potential for increasing representation in the sciences by these underrepresented groups. An exchange program between USC and Dartmouth will be established that will allow promising young USC undergraduates to experience research in both the Guerinot and Connolly labs. First-generation, low-income undergraduate students from groups under-represented in the sciences will be recruited and trained in the latest genomic, molecular and biochemical methods.