Forward genetics has been enormously empowered by the ability to rapidly identify mutations responsible for phenotype when they occur on a defined, homozygous genetic background. This situation applies in model organisms such as inbred mice and drosophila, for which reference sequences also exist. Core B is dedicated to the identification of ENU- and EMS-induced mutations in these species. The Resequencing Core was developed to support the first cycle of funding was the precursor upon which Core B is based. As originally constructed, the resequencing core did not have access to powerful mutation finding methods. Within the framework of this earlier core, robotic systems for validation sequencing were developed, so that mutations within coding sequences or splice junctions could be found in circumscribed critical regions. Later, the same methods were adapted to the validation of putative mutations identified through SOLiD sequencing. At present, the Sequencing Core is in full operation, and SOLiD calls are automatically amplified and then confirmed or excluded as candidates. Core B will continuously update, expand, and perfect software for mutation identification, a crucial element of Projects 1 and 2. Within Core B we will also operate a pipeline for the public release of mutations found in the course of our work. These incidental mutations will form the core of an allelic series in the mouse and drosophila genomes, and several thousand such mutations have already been catalogued within Mutagenetix, contributed by our group and by the Goodnow group at Australian National University. As technology improves with the advent of SOLiD 5500XL technology and its successors, validation sequencing may become less central to Core B, and greater emphasis will accordingly be placed upon whole genome sequencing alone as a means of finding mutations. [Indeed, capillary validation sequencing may be replaced entirely by methods such as Ion Torrent sequencing]. Core B will also be responsible for bulk segregation analysis, selected as the mapping technique of choice for its speed and low cost.
Core B is an essential pillar of the Program Project, offering cutting-edge sequencing technology to all of the participating groups. These technologies give a new way of finding mutations rapidly, speeding the achievement of project objectives many fold. This will lead to more rapid implementation of concrete measures in the treatment of viral disease.
| 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, João T; Imler, Jean-Luc (2016) The diversity of insect antiviral immunity: insights from viruses. Curr Opin Microbiol 32:71-76 |
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