Final Activity Report Summary - NICRYPTO (Nickel homeostasis in the human pathogenic fungus Cryptococcus neoformans) Cryptococcus neoformans is a fungus that usually grows in the soil but can cause disease in humans that have an impaired immune system. There is interest in understanding how an organism that usually lives in the soil is able to survive in the human body. Such knowledge will help in the development of new therapeutic treatments. Important for the ability of C. neoformans to cause disease is the enzyme urease, which provides the cell with a source of nitrogen. Urease activity depends on the metal ion nickel, which forms its active centre. Therefore, it is likely that nickel will also be important for the ability of C. neoformans to infect humans.We are interested in understanding how C. neoformans acquires nickel and how it becomes incorporated into the urease enzyme. The objective of this work has been to identify proteins that are involved in nickel metabolism in C. neoformans and determine if and how they are regulated. We have identified a transporter that is involved in the uptake of nickel and a protein that is potentially involved in the insertion of nickel into urease. Mutants that lack either of these proteins do not exhibit urease activity suggesting that the disruption of nickel acquisition and distribution in C. neoformans will inhibit its ability to cause disease.