Xenopus laevis is one of the best ectothermic vertebrate models for studying the phylogeny and ontogeny of the immune system. The evolutionary distance of X. laevis from mammals permits distinguishing species-specific adaptations from more conserved features of the immune system. X. laevis, provides a unique, versatile, non-mammalian model with which to study humoral and cell-mediated immunity in the context of MHC restricted and unrestricted recognition, ontogeny, and phylogeny, and against tumors, viruses, and bacteria. In particular, the developmentally regulated acquisition of MHC class I molecules during metamorphosis and the ease with which one can experimentally manipulate embryos and larvae prior to expression of class I and other adult-specific antigens allows one to address questions about MHC restriction, autoimmunity, and the development of self-tolerance that can not be easily studied in other animal models. Studies with X. laevis over several decades have resulted in the generation of many invaluable research tools including MHC-defined isogenetic clones and inbred strains of animals, transgenic lines, cell lines, monoclonal antibodies, and cDNA probes that need to be preserved, enriched and made available to the scientific community. The broad objective of this renewal proposal, therefore, is to safeguard, promote and further develop X. laevis as an important model for biomedical research in general, and immunology, in particular. As in the original proposal, two major aims are proposed: (1) Maintenance, improvement and advertisement of our X. laevis facility by continuing to maintain and improve the performance and quality of our resource;by providing animals, not commercially available, and reagents upon request;by assisting, training, and informing scientists and students about X. laevis;and by disseminating information, advertising and interacting with the scientific community through a web site. (2) Development of new experimental animals, methodologies, and reagents by producing a new collection of isogenetic clones MHC and minor-H-antigen defined;by adapting transgenesis techniques and generating transgenic, which are isogenetic clones, expressing fluorescent reporter genes in lymphoid tissues (e.g., thymus, spleen) or leukocytes;by developing in vivo knockdown by RNA interference using transgenesis to reveal the function of immunologically-relevant genes;and by generating new X. laevis-specific antibodies (Abs) recognizing immunologically-relevant molecules.

Public Health Relevance

The overall objective of this renewal application is to safeguard and promote the frog Xenopus laevis, as an important non-mammalian comparative model for biomedical research in general, and immunology, in particular. We are proposing to continue the maintenance and the development of this unique non-mammalian resource facility for biomedical research for the benefit of the whole scientific community.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Resource-Related Research Projects (R24)
Project #
5R24AI059830-10
Application #
8511537
Study Section
Allergy & Clinical Immunology-1 (AITC)
Program Officer
Leitner, Wolfgang W
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$249,096
Indirect Cost
$87,869
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Cheng, Kwang; Escalon, B Lynn; Robert, Jacques et al. (2014) Differential transcription of fathead minnow immune-related genes following infection with frog virus 3, an emerging pathogen of ectothermic vertebrates. Virology 456-457:77-86
Robert, Jacques; Edholm, Eva-Stina (2014) A prominent role for invariant T cells in the amphibian Xenopus laevis tadpoles. Immunogenetics 66:513-23
Grayfer, Leon; De Jesús Andino, Francisco; Robert, Jacques (2014) The amphibian (Xenopus laevis) type I interferon response to frog virus 3: new insight into ranavirus pathogenicity. J Virol 88:5766-77
Edholm, Eva-Stina; Goyos, Ana; Taran, Joseph et al. (2014) Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae. Immunogenetics 66:411-26
Haynes-Gilmore, Nikesha; Banach, Maureen; Edholm, Eva-Stina et al. (2014) A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model. Carcinogenesis 35:1807-13
Sifkarovski, Jason; Grayfer, Leon; De Jesús Andino, Francisco et al. (2014) Negative effects of low dose atrazine exposure on the development of effective immunity to FV3 in Xenopus laevis. Dev Comp Immunol 47:52-8
Edholm, Eva-Stina; Grayfer, Leon; Robert, Jacques (2014) Evolution of nonclassical MHC-dependent invariant T cells. Cell Mol Life Sci 71:4763-80
Robert, Jacques; Grayfer, Leon; Edholm, Eva-Stina et al. (2014) Inflammation-induced reactivation of the ranavirus Frog Virus 3 in asymptomatic Xenopus laevis. PLoS One 9:e112904
Suurvali, Jaanus; Robert, Jacques; Boudinot, Pierre et al. (2013) R4 regulators of G protein signaling (RGS) identify an ancient MHC-linked synteny group. Immunogenetics 65:145-56
Nedelkovska, Hristina; Robert, Jacques (2013) Hsp72 mediates stronger antigen-dependent non-classical MHC class Ib anti-tumor responses than hsc73 in Xenopus laevis. Cancer Immun 13:4

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