Viral resistance

Bruken av genomikk i lakseavl har bidratt til en fisk med god vekst, økt robusthet og sykdomsresistens. Identifiseringen av kausale resistensgener og polymorfismer hos atlantisk laks er imidlertid utfordrende på grunn av det delvis tetraploide genomet. Genredigering har nå blitt et viktig verktøy, og mange forskningsmiljøer jobber intensivt for å etablere metoder for å analysere et stort antall gener samtidig, for å forstå genotype - fenotype-interaksjon. I dette prosjektet søker vi å forstå vert-patogen interaksjon mellom ulike virusisolater og om cellekulturmetoder korrelerer med funn fra smitteforsøk. Videre tar prosjektet sikte på å utvikle verktøy for å studere kausalitet på genomnivå og hvordan resultatene kan brukes til avl for sykdomsresistens.

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.