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- Iron is an essential mineral in our food. Therefore children are encouraged to eat iron-rich green vegetables such as spinach advertised in Popeye cartoons. Plant foods are the primary source of our dietary iron which they obtain directly from the soil. Plants are extremely efficient at mining the soil for iron, but they will take up no more than they require for their own needs. This is because iron, in its free form, is extremely toxic. As soon as iron enters the cell, it is bound by chaperone proteins to carry iron safely around the cell and then immediately incorporate it in enzymes to function as catalysts. Some iron can also be stored in specific proteins or cell compartments. Balancing the uptake, use and storage of iron is called homeostasis. Central to maintaining homeostasis is an iron sensor, which signals to regulators of gene expression to alter the levels of transporters (and other iron homeostasis proteins). Iron sensors have been described in bacteria, in yeast and in mammals. However, we still do not know how iron is sensed in plants, or which proteins function as iron sensors. However, we do know that the expression of iron homeostasis genes is very tightly regulated in plants, so there must be a very sensitive Fe sensor. Extensive analyses of gene expression networks in plants grown under iron-deficient conditions has turned up three candidate proteins for the iron sensor. The proteins are related in sequence but are present in different tissues. What makes them good candidates is their pattern of regulation within the iron regulatory network, their similarity to an iron-sensing protein in mammals, and several iron binding protein domains. In the proposed project we would like to confirm the role of these proteins, named IRS1, IRS2 and BTS, in iron homeostasis. First, we will measure iron binding to the separate protein domains, what form the iron is in and how strong the binding is. A relatively weak binding constant is expected in sensor proteins. We will also try and elucidate how the proteins orchestrate downstream signalling events. They are likely to interact with other proteins, and we will use established methods to identify these interaction partners. To feed the growing world population, it has been suggested that we should all eat less meat. However, if we cut down on this rich source of iron, this could lead to iron deficiency anaemia, which is already common among girls and women in the UK and widespread in the developing world. Plants can provide enough iron if our diet is rich in green vegetables and pulses. This is not always the case, therefore it would be beneficial to increase the amount of iron in staple foods such as wheat (for bread) and potatoes. The only way to do this, is to trick the plant in taking up more iron than it needs, and enable a large iron storage capacity. For this, we need first find the iron sensor, so we can alter its sensitivity and signalling capacities.