After many years of working on protein folding and related issues, the Creamer lab is now applying its expertise to the characterization of the function and conformational properties of intrinsically disordered regions (IDRs) within proteins. IDRs are regions of protein sequence that do not appear to adopt a well-defined structure. We have chosen calmodulin (CaM) and its targets as model systems to study the function of IDRs. Our current studies are focused on calcineurin (CaN), a Ser/Thr phosphatase that is activated by CaM binding. CaN plays essential roles in memory development and retention, cardiac growth, and immune system activation. It has been implicated in numerous disorders including Down syndrome, cardiac hypertrophy, and autoimmune disorders. The regulatory domain of CaN, which is a CaM substrate, is an IDR. We are investigating the CaM-CaN interaction and how this regulates CaN function. We are extending this work to include other regulators of CaN including Rcan1, a protein that plays a role in Down syndrome.