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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

CRISPR-Cas9 base editing approaches to discover ubiquitination events promoting flavivirus infection

Completed
Institution
Icahn School of Medicine at Mount Sinai, NY
Principal investigator
Jeffrey R Johnson
Funding
$246K
Duration
2024–2026
Open portfolio

Moonbase score

Still being scored

Abstract

PROJECT SUMMARY Viruses extensively remodel the cells that they infect. Ubiquitination networks are frequent targets of viral manipulation, but compared to other modifications such as phosphorylation, our general understanding of functional ubiquitination events is limited. In this project, we will apply CRISPR-Cas9 base-editing approaches to assess ubiquitination site function in a systematic, unbiased manner in the context of flavivirus infection. We have previously quantified ubiquitination responses to West Nile virus (WNV) infection, identifying hundreds of modulated ubiquitination targets with unknown functions. In Specific Aim 1, we will systematically introduce mutations at these ubiquitinated residues and assess the impact on WNV infection in a pooled base-editing screening format. In Specific Aim 2, we will apply base editing to perturb ubiquitination enzyme active sites for enzymes that physically interact with flavivirus NS5 proteins. Successful completion of these aims will discover novel pathways that promote flavivirus infection and will provide CRISPR-Cas9 base-editing resources tailored towards research questions in virology and ubiqutination functions.

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NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR21Molecular and Cellular Biology of Virus Infection Study Section[MCV]infectionubiquitinationeditingbase editingflavivirusspecific aimcrispr-wnv

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