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Viral resistance

Alternative title: VirusResistens

Awarded: NOK 1.8 mill.

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Project Period:

2022 - 2025

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The use of genomics in Atlantic salmon breeding has vastly improved production performance and disease resistance during the last decade. However, the identification of causative genes and polymorphisms underlying specific phenotypes has been difficult because the Atlantic salmon genome is partially tetraploid and complex. Further, compared to model fish species such as zebrafish and madaka, available methods for investigating gene function have been lagging behind. Consequently, there is now a large push to establish more advanced technology to facilitate functional studies which can help out establishing a deeper understanding on genotype - phenotype correlation. Most recently, a new version of the A. salmon genome was released and new protocols, transferred from model fish species and human science, have been established for Atlantic salmon. In this project we seek to make use of and optimize state of the art methods for improving knowledge on host pathogen interaction and resistance mechanisms.

The use of genomics in salmon breeding has resulted in the identification of QTLs for a number of important viral and bacterial pathogens. But still it is a challenge to fine map the chromsomal regions and identify the causative mutations and underlying genes explaining the QTL phenotype. This inability is mostly caused by the lack of high throughput methods for functional analysis of gene and polymorphisms. However, a better genome assembly and new methods for genetic manipulation of gene expression, function and molecular tagging, may now facilitate novel studies on important Atlantic salmon diseases. The latter can be achieved by genome wide CRISPR analysis (GeCKO screening), which relies on simultaneous delivery of thousands of targeting guides that typically requires lentiviral transduction of the CRISPR components, followed by a challenge test with the pathogen of choice. Post screening, only cells with a beneficial mutation survive and the corresponding gene can be identified by deep sequencing. One major problem remains, lentivirus are not able to enter Atlantic salmon cells. Thus, the virus vector must be adapted for a new species. In brief, this project aims at describing the molecular mechanisms host-pathogen interactions in Atlantic salmon and develop and optimize tools for conducting genome wide high throughput methods for studies on causality.

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