Description du projet
Modéliser les réponses des lymphocytes T de la population
Le projet CELLULO‑EPI, financé par l’UE, entend mener une recherche approfondie sur le processus évolutif que subissent les cellules immunitaires sous l’influence de paramètres tels que l’âge, le genre et la période d’infection. L’approche interdisciplinaire proposée appelée «celluloépidémiologie» combine l’étude d’immunoréactions cellulaires spécifiques face aux agents pathogènes à l’échelle de la population avec une modélisation mathématique. Les modèles seront optimisés et testés en utilisant des données sur les lymphocytes T pour les agents pathogènes issus de 500 personnes avec des premières infections connues comme le chikungunya et la rougeole, et des données longitudinales sur des personnes à nouveau exposées à la varicelle et au parovirus B‑19. Cette étude permettra de bien mieux comprendre le développement d’un système immunitaire et le fonctionnement des maladies infectieuses.
Objectif
As a paediatrician who specialized in immunology and as a physicist who specialized in mathematical modeling of infectious diseases, I want to introduce with this project a paradigm shift in infectious disease epidemiology through the concept of celluloepidemiology.
Celluloepidemiology is a term I invented to describe my proposed interdisciplinary approach combining unique cellular immune responses against pathogens on a population level with mathematical modeling, thereby generating unique and otherwise not obtainable multidimensional T-cell profiles.
CELLULO-EPI will develop and use such a highly innovative model to simulate how T-cells against pathogens evolve in a synthetic population as a function of age, gender, time since infection and other relevant variables. This model will be parameterized and fitted by cross sectional T-cell data against a wide set of pathogens from 500 individuals (sampled again after 1 year), unique data from individuals with known first infections with dengue and measles and longitudinal data from individuals re-exposed to chickenpox and parvovirus B19.
The insights of CELLULO-EPI will be pivotal for public health. One important example: Varicella-zoster virus (VZV) causes chickenpox but also shingles after VZV reactivation. Vaccination can prevent chickenpox, but the predicted increase in shingles incidence has blocked chickenpox vaccination in many EU-countries. Indeed, re-exposure to chickenpox is hypothesized to protect against shingles through boosting of T-cells. Unfortunately, none of the available epidemiological or immunological tools allow for adequate validation of the boosting hypothesis. However, CELLULO-EPI will be able to solve this persisting VZV vaccination dilemma. Furthermore, CELLULO-EPI will also redefine infectious disease epidemiology, for example by allowing us to back-calculate the time since last exposure.
I am convinced CELLULO-EPI can revolutionize infectious disease epidemiology and public health.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
2000 Antwerpen
Belgique