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
Grogan, Laura F; Robert, Jacques; Berger, Lee et al. (2018) Review of the Amphibian Immune Response to Chytridiomycosis, and Future Directions. Front Immunol 9:2536
Robert, Jacques (2018) Frog's DCs have it all in one. Eur J Immunol 48:415-418
Neely, Harold R; Guo, Jacqueline; Flowers, Emily M et al. (2018) ""Double-duty"" conventional dendritic cells in the amphibian Xenopus as the prototype for antigen presentation to B cells. Eur J Immunol 48:430-440
Edholm, Eva-Stina; Banach, Maureen; Hyoe Rhoo, Kun et al. (2018) Distinct MHC class I-like interacting invariant T cell lineage at the forefront of mycobacterial immunity uncovered in Xenopus. Proc Natl Acad Sci U S A 115:E4023-E4031
Banach, Maureen; Edholm, Eva-Stina; Robert, Jacques (2017) Exploring the functions of nonclassical MHC class Ib genes in Xenopus laevis by the CRISPR/Cas9 system. Dev Biol 426:261-269
De Jesús Andino, Francisco; Lawrence, B Paige; Robert, Jacques (2017) Long term effects of carbaryl exposure on antiviral immune responses in Xenopus laevis. Chemosphere 170:169-175
Banach, Maureen; Robert, Jacques (2017) Tumor immunology viewed from alternative animal models-the Xenopus story. Curr Pathobiol Rep 5:49-56
Jacques, Robert; Edholm, Eva-Stina; Jazz, Sanchez et al. (2017) Xenopus-FV3 host-pathogen interactions and immune evasion. Virology 511:309-319
Edholm, Eva-Stina; Rhoo, Kun Hyoe; Robert, Jacques (2017) Evolutionary Aspects of Macrophages Polarization. Results Probl Cell Differ 62:3-22
Nakai, Yuya; Nakajima, Keisuke; Robert, Jacques et al. (2016) Ouro proteins are not essential to tail regression during Xenopus tropicalis metamorphosis. Genes Cells 21:275-86

Showing the most recent 10 out of 67 publications