H2020Индивидуална стипендия2021–2023

DENGUE · An imaging-based systems approach to understand the neuroimmunological manifestations of Dengue infection in humans

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

Период: 2021-09-01 → 2023-08-31
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Вирусът на денге и влиянието му върху взаимодействието между имунните и нервните клетки в човешкия мозък се анализират чрез специални лабораторни модели. Това помага за разбирането на тежките неврологични симптоми и подпомага разработването на по-ефективни лекарства.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

An imaging-based systems approach to understand the neuroimmunological manifestations of Dengue infection in humans

Dengue viral infection (DENV) poses a significant global health challenge, infecting approximately 400 million people annually, with around 96 million exhibiting clinical symptoms. It represents the world's fastest spreading tropical disease, with severe forms like Dengue Haemorrhagic Fever (DHF) causing the majority of the 250,000 annual fatalities. While the disease primarily targets immune cells, its severest forms manifest neurological symptoms such as encephalopathy and encephalitis. Despite this significant burden, treatments are limited to supportive care, and vaccines are only partially effective. The project aims to address critical knowledge gaps concerning DENV's neuro-immunological effects, and the lack of suitable human neuro-immune models and platforms for large-scale functional drug studies that hinder the development of effective treatments. To tackle these challenges, the project proposed to create an autologous human model mimicking the neuro-immune interface disrupted in severe dengue cases. The overall objectives were to establish donor-specific immune and neural cell culture systems, assess the neuro-immunomodulatory effects of various drug classes in these cell cultures, and develop multi-omic sequencing and machine learning methods that allow integration of imaging and molecular data. The project's outcomes are expected to enable future studies that investigate neuro-immune crosstalk and aid the development of personalized in vitro models for neuro-immune disorders, pathogenic infections, and cancer.

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

Цел на проекта

Dengue is a mosquito-borne illness for which approximately half of the world’s population is at risk, with close to 100 million symptomatic cases per year. Classified as a Neglected Tropical Disease (NTD) that disproportionately affects the world’s most vulnerable populations, basic and translational research regarding the cellular consequences of Dengue virus (DENV) infection is vastly under-represented. Even fewer studies examine the neuro-immunological manifestations of severe dengue which embodies the most fatal and dangerous form of disease. However, as the central nervous system (CNS) is inaccessible in humans with the rare exceptions of post-mortem brain tissue, the lack of appropriate human models and platforms to test large-scale functional perturbations have hindered efforts to conduct human studies in the context of DENV infection. Here, we propose to develop an autologous human model that represents the DENV neuro-immune interface by employing a two-step reprogramming method that differentiates donor blood to derive donor-matched induced neuronal cells (iNs) via induced pluripotent stem cells (iPSCs).We will then establish a DENV infection paradigm of both neural and immune lineage cells, and systematically screen for potential neuro- and immune-modulators of DENV pathogenicity and cell-cell interactions. High-content image-based profiling and convolutional neural networks (CNNs) will be implemented to untangle the contributions of different cell types and learn heterogeneous cell-type-specific or donor-specific phenotypes. Finally, for promising candidate modulators that either affect cellular DENV pathogenicity, those that alter the baseline neuro-immune interactions, or those in which the drug response differs among donors - we will conduct matched transcriptomic profiling to uncover functional gene networks that regulate features of DENV-mediated perturbation of neuro-immune homeostasis.

Оригинален текст от CORDIS (на английски).

Участници

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichКоординаторШвейцария