H2020Индивидуална стипендия2019–2020

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

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2019-01-01 → 2020-12-31
Финансиране от ЕС: 200 195 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Чревните клетки и техните фактори се анализират чрез CRISPR технология, за да се разбере как ентеровирусите навлизат и се размножават в тях. Това е важно, защото в момента няма терапии срещу тези инфекции, които застрашават милиони хора.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

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

Managing infection diseases rely on the availability of medical treatment. While medication, including vaccines, have been developed and are successfully used for treating and protecting individuals, to date there are still many infections for which treatment options are limited or not available. Human Enterovirus (HEV) infections are of public health concern as globally millions of people become infected each year. Most HEV infections cause only mild symptoms, however severe pathologies can occur, especially in immunocompromised individuals as well as in infants, children and the elderly. To date, no enteroviral therapies exist and new strategies are urgently needed to counter HEV outbreaks and severe pathologies in populations at risk, in particular given the fact that many countries have stopped vaccinating against the most prominent member of the HEV family, polio. This project aims at identifying host factors crucial for the HEV life cycle by combining for the first time, state-of-the-art high-throughput CRISPR technology with physiologically relevant primary cultures of human intestinal epithelial cells (organoids). The ultimate goal is to identify novel host factors that are key regulators of the viral life cycle and might pave the way to the discovery of novel drug targets for a broad-spectrum treatment against HEV infections. Two overall objectives have been defined for this project, which are (1) identifying novel host factors essential for the life cycle of human enteroviruses (HEVs) upon infection of human intestinal organoids, and (2) deciphering the roles of these identified host factors in promoting HEV infection in humans.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

KOBENHAVNS UNIVERSITET · KOBENHAVNКоординаторДания