The goal of this renewal application is to support and develop the world's most comprehensive research resource specializing in the use of the amphibian Xenopus laevis as a multi-faceted experimental platform for biomedical and immunological research and for the benefit of the whole scientific community. Interests and medical relevance of X. laevis are due to the remarkable similarity of its immune system with that of human, the accessibility to experimentation at all developmental stages, as well as the availability of large genetic and genomic resources, invaluable MHC-defined inbred strains and clones of frogs and tools such as lymphoid tumor cell lines, monoclonal antibodies, MHC tetramers and batteries of validated PCR primers for immune-relevant genes. These animals and reagents that are not commercially available need to be preserved, enriched, and made available to the scientific community. As in previous proposals, two major main aims are proposed: (1) Preserving and promoting the X. laevis research resource for immunobiology by keeping on managing and distributing animal stocks and reagents to laboratories in the US and abroad. We will maintain and further optimize the diversity, quality, productivity and welfare of our animals. We will continue to assist, train and inform scientists, students and educators interested in using X. laevis as a research model. We will continue to foster the accessibility and public awareness of the resource by frequently updating our web site by which we disseminate information to the scientific community. We will cultivate communication, networking and interactions with other Xenopus resources in US and in the world. (2) Developing new methodologies and generating new experimental animals and reagents, with the major goal of integrating and exploiting the recent remarkable advance and success of the CRISPR/Cas9- based genome editing technology to generate transgenic (Tg) Xenopus. This has been identified as a priority by the Xenopus community. The specific objectives will be: (i) To adapt the CRISPR/Cas9 system for immune gene loss-of-function by transgenesis; (ii) To develop reagents of high specificity for key immune receptors and factors; (iii)To generate and characterize fluorescent Tg reporter MHC-defined inbred lines and clones; and (iv) To continue developing X. laevis tadpoles for real time intravital microscopy. In addition to maintaining a research platform that is crucial for the Xenopus scientific community, this project promotes the development of new approaches and technologies that can be rapidly and broadly applied for innovative insights into tissue and organ physiology, immunology and developmental biology. The development and application of these tools and technologies will contribute to the efforts of the Xenopus community assisted by the NIH to establish Xenopus as a relevant model for biomedical research.

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 that includes animals, reagents, information and training opportunity 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 #
5R24AI059830-17
Application #
9982055
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Singleton, Kentner L
Project Start
2004-06-01
Project End
2023-07-31
Budget Start
2020-08-01
Budget End
2021-07-31
Support Year
17
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
School of Medicine & Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
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
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
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

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