A Fogarty fellowship is sought to support a visit by Dr. Argon, from the Univ. of Chicago, to the lab of Dr. Ciechanover at the Techion, Israel, as a first phase of a collaborative effort between the two. The purpose of the collaboration is to employ the complementary tools, reagents and expertise of the two labs in the study of light chain amyloidosis at the cellular and biochemical level. We will define the requirements and parameters of intracellular degradation of misfolded light chain via the proteasome pathway, as this is one way for the cell to cope with the aggregating protein. We will also test the hypothesis that intracellular inclusion body formation is an alternative quality control mechanism, when degradation fails to dispose of the protein. Third, we will assay the roles of the molecular chaperones HSP70 and HSP90 in targeting the amyloid light chains to either the degradation or the aggregation pathway. The significance of these studies is in illuminating the basic biology underlying amyloidosis and other protein aggregation diseases, for which there is currently only symptomatic treatment. Three visits are planned for a total of 12 months over a three-year period.
|Elkabetz, Yechiel; Ofir, Ayala; Argon, Yair et al. (2008) Alternative pathways of disulfide bond formation yield secretion-competent, stable and functional immunoglobulins. Mol Immunol 46:97-105|