Infection of the human intestine by enteroviruses: A CRISPR-based screening approach

Información del proyecto

EvISC

Identificador del acuerdo de subvención: 795904

DOI

10.3030/795904

Proyecto finalizado el 31 Agosto 2019

Fecha de la firma de la CE 7 Marzo 2018

Fecha de inicio 1 Enero 2019

Fecha de finalización 31 Diciembre 2020

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 200 194,80

Aportación de la UE

€ 200 194,80

Coordinado por

KOBENHAVNS UNIVERSITET
Denmark

Objetivo

Enterovirus infections are of public health concern as globally millions of people become infected each year. Enteroviruses (HEV) are an assemblage of highly diverse positive-stranded RNA viruses that belong to the Picornaviridae family. Four out of the 13 known enterovirus species are human pathogens, with poliovirus being the most prominent member. The entry point for these viruses is the gastrointestinal or the respiratory tract from where they can spread to other organs and cause severe pathologies. Vaccines exist only against polio and no therapies are currently available against any HEV. Thus, there is a great need for new antivirals.
I aim to identify host factors crucial for the HEV life cycle by performing a whole genome CRISPR loss-of-function screen in primary cultures of human intestinal epithelial cells. Importantly, the lytic nature of HEVs will allow a straightforward selection of cells that survive virus infection upon small guide RNA-mediated deletion of host genes that support HEV infection. This interdisciplinary project demands expertise both in stem cell, enterovirus biology and host-pathogen interaction, which is provided by the Jensen lab (host), the Tapparel lab (partner) and myself, respectively.
Through access to intestinal stem cells and organoids from various donors and multiple HEVs I have the unique possibility to dissect host-enterovirus interactions by taking host and virus variations into account. By integrating this data, I will be able to dissect tropism both from a host and a pathogen perspective, and identify host factors that are necessary for HEV infection. This knowledge will contribute to the discovery of novel drug targets for broad-spectrum therapies against HEV infections and moreover provide me with the unique opportunity to move forward in academia and establish my own research group.

Ámbito científico (EuroSciVoc)

• ciencias médicas y de la salud › ciencias de la salud › enfermedad infecciosa › virus de ARN
• ciencias médicas y de la salud › ciencias de la salud › salud pública y medio ambiental
• ciencias médicas y de la salud › biotecnología médica › tecnologías celulares › células madre
• ciencias médicas y de la salud › medicina básica › farmacología y farmacia › medicamento › vacuna
• ciencias médicas y de la salud › medicina básica › farmacología y farmacia › medicamento › antivírico

Palabras clave

• Human intestinal organoids
• human intestinal stem cells
• CRISPR
• Cas9
• Host-Pathogen interactions
• enterovirus

Programa(s)

• H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions PROGRAMA PRINCIPAL
  
• H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
  

Tema(s)

• MSCA-IF-2017 - Individual Fellowships
  

Régimen de financiación

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

Convocatoria de propuestas

H2020-MSCA-IF-2017

Coordinador

KOBENHAVNS UNIVERSITET

• Aportación neta de la UEn: € 200 194,80
• Dirección: NORREGADE 10 ; 1165 KOBENHAVN ; Dinamarca
• Región: Danmark › Hovedstaden › Byen København
• Tipo de actividad: Higher or Secondary Education Establishments
• Coste total: € 200 194,80