Ron

Like cellular proteins, viral proteins generated during the course of an infection are likely to require chaperones to attain the native, functional state. I am examining the chaperone requirements of two members of the Picornavirus family, Poliovirus and Rhinovirus. The interaction of proteins from these two viruses with the chaperone machinery is likely to be interesting because quickly after infection host protein synthesis is turned off and only viral proteins are produced. Therefore, the repertoire of client proteins for chaperones will consist of a very limited, high abundance pool of viral proteins. In addition, the assembly of higher order complexes, such as the viral capsid, may require chaperones for formation.

2) Cross presentation:

Direct presentation refers to a mechanism by which peptides generated from degradation of endogenous cellular proteins are displayed on the cell surface in complex with MHC class I. This mechanism enables the immune system to "see" what is occurring inside the cell so that infected or transformed cells can be rapidly identified and eliminated. Cross presentation, on the other hand, is a mechanism by which cells display peptides from an exogenous source (i.e. an infected neighboring cell) on their MHC class I. While direct presentation is found in nearly all cell types, Cross presentation mainly occurs in cells of the immune system which specialize in antigen presentation. I am using an in vitro system to try and understand the mechanism of Cross Presentation

Publications:

[1] Geller R, Vignuzzi M, Andino R, Frydman J. Evolutionary constraints on chaperone-mediated folding provide an antiviral approach refractory to development of drug resistance. Genes Dev 2007;21 (2):195-205.
[2] Tam S, Geller R, Spiess C, Frydman J. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit- specific interactions. Nat Cell Biol 2006;8 (10):1155-62.
[3] Khakoo SI, Geller R, Shin S, Jenkins JA, Parham P. The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer. J Exp Med 2002;196 (7):911-21.
[4] Geller R, Adams EJ, Guethlein LA, Little AM, Madrigal JA, Parham P. Linkage of Patr-AL to Patr-A and- B in the major histocompatibility complex of the common chimpanzee (Pan troglodytes). Immunogenetics 2002;54 (3):212-5.