The Developmental Genomics Section has been using a combination of zebrafish genetics and molecular embryology to study ear development and hearing regeneration. We do this through studying mutations that affect ear development or regeneration. One mutation that we are studying affects the regenerative ability in several tissues of the zebrafish embryo including the hair cells of the inner ear. We are cloning the transcript and establishing the subcellular localization of the protein and determining the function for the protein. We have initiated research on hair cell regeneration in adult zebrafish. We are exposing zebrafish to sound at high enough decibles to cause damage. We have measured the changes in gene expression that occur over a recovery period of several days and are in the process of defining the genetic network needed for hair cell regeneration. We are also using transgenic lines where specific cell types are marked with GFP. These GFP positive cells are isolated and the transcriptome determined. Another focus of the lab is to develop tools for studying gene expression on a genome wide scale. We have developed a technique for rapidly mapping the integration sites for retroviruses and transposable elements and we are now in the second phase of a process to map thousands of proviral integrations in the zebrafish germline to create an archived zebrafish mutant resource. We have completed the first phase to map 1600 retroviral integrations and test the efficacy of mutagenesis. This phase established the framework for generating the resource, and determine the number of total fish necessary to map 100,000 retroviral integrations (which will disrupt an estimated 12,000 genes). We are now in the process of generating the fish containing the 100,000 retroviral integrations. We have recently frozen the first 1500 F1 fish for our archive. Mapping of the retroviral integrations in the first 16% of the resource is underway.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2009
Total Cost
$1,581,005
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
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Giannelou, Angeliki; Wang, Hongying; Zhou, Qing et al. (2018) Aberrant tRNA processing causes an autoinflammatory syndrome responsive to TNF inhibitors. Ann Rheum Dis 77:612-619
Tseng, Wei-Chia; Loeb, Hannah E; Pei, Wuhong et al. (2018) Modeling Niemann-Pick disease type C1 in zebrafish: a robust platform for in vivo screening of candidate therapeutic compounds. Dis Model Mech 11:
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