The present Core C (Cryopreservation and Stem Cell Biology Core), evolved from a predecessor devoted strictly to cryopreservation. Core C is far more sophisticated than its predecessor, and is already in full operation. The recent development of inducible pluripotent stem cell technology permits the regeneration of whole mice from individual cells with specific phenotypes, including cells identified through mutagenesis and phenotypic screening. The potential to screen the mammalian genome in depth for cell-autonomous phenotypes will be exploited in Project 1. Toward this end, the Core has already developed reprogrammable mice to facilitate the induction of iPS cells from a small population of MEFs selected for resistance to infection by Rift Valley Fever Virus (RVFV). Dedifferentiation is now routinely accomplished in our lab using doxycycline, once phenotypes of interest have been identified in mouse embryonic fibroblasts (MEFs). We will likely apply the same methodology to other cell types as well, including macrophages. Core C has already shown that mutagenized MEFs can be used to produce IPS cells, and in turn to produce viable mice that yield germline transmission of ENU-induced mutations. Other techniques have also been perfected to support the efforts of Project 1, and the exchange of mice between Osaka and Dallas. These include the use of intracytoplasmic sperm injection (ICSl) to force mapping crosses in low fertility strains, and the cryostorage of sperm, embryos, and IPS clones as needed for our collective work. A specialized facility for all of these techniques is essential for the success of Project 1, and the Program Project as a whole. This Core will facilitate the exchange of mice between Dallas and Osaka.

Public Health Relevance

Core C has a dual function, permitting ultra-high efficiency mutagenesis of the mouse genome to find key proteins in the viral response and permitting rapid exchange of mice between Osaka and La Jolla. Both of these functions will contribute to public health by allowing the discovery of genes that impede viral proliferation and genes that are essential for it. This will allow deeper understanding of how viral infections progress and how they can be thwarted.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI070167-08
Application #
8678823
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
City
Dallas
State
TX
Country
United States
Zip Code
75390
Goto, Akira; Okado, Kiyoshi; Martins, Nelson et al. (2018) The Kinase IKK? Regulates a STING- and NF-?B-Dependent Antiviral Response Pathway in Drosophila. Immunity 49:225-234.e4
Maeda, Kazuhiko; Akira, Shizuo (2017) Regulation of mRNA stability by CCCH-type zinc-finger proteins in immune cells. Int Immunol 29:149-155
Satoh, Takashi; Nakagawa, Katsuhiro; Sugihara, Fuminori et al. (2017) Identification of an atypical monocyte and committed progenitor involved in fibrosis. Nature 541:96-101
Kozaki, Tatsuya; Komano, Jun; Kanbayashi, Daiki et al. (2017) Mitochondrial damage elicits a TCDD-inducible poly(ADP-ribose) polymerase-mediated antiviral response. Proc Natl Acad Sci U S A 114:2681-2686
Mager, Lukas Franz; Koelzer, Viktor Hendrik; Stuber, Regula et al. (2017) The ESRP1-GPR137 axis contributes to intestinal pathogenesis. Elife 6:
Mussabekova, Assel; Daeffler, Laurent; Imler, Jean-Luc (2017) Innate and intrinsic antiviral immunity in Drosophila. Cell Mol Life Sci 74:2039-2054
Kuhn, Lauriane; Majzoub, Karim; Einhorn, Evelyne et al. (2017) Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS. G3 (Bethesda) 7:2249-2258
Takahama, Michihiro; Fukuda, Mitsunori; Ohbayashi, Norihiko et al. (2017) The RAB2B-GARIL5 Complex Promotes Cytosolic DNA-Induced Innate Immune Responses. Cell Rep 20:2944-2954
Lamiable, Olivier; Arnold, Johan; de Faria, Isaque Joao da Silva et al. (2016) Analysis of the Contribution of Hemocytes and Autophagy to Drosophila Antiviral Immunity. J Virol 90:5415-5426
Marques, JoĆ£o T; Imler, Jean-Luc (2016) The diversity of insect antiviral immunity: insights from viruses. Curr Opin Microbiol 32:71-76

Showing the most recent 10 out of 87 publications