Descrizione del progetto
Creare modelli di risposta delle cellule T nella popolazione
Il progetto CELLULO-EPI, finanziato dall’UE, si propone di condurre una ricerca approfondita sul processo evolutivo cui sono sottoposte le cellule immunitarie sotto l’influenza di parametri quali età, sesso e tempo trascorso dall’infezione. L’approccio interdisciplinare proposto, definito «celluloepidemiologia», combina lo studio di specifiche risposte immunitarie delle cellule contro gli agenti patogeni a livello di popolazione, utilizzando modelli matematici. I modelli saranno ottimizzati e testati utilizzando i dati di cellule T per agenti patogeni provenienti da 500 persone con prime infezioni accertate da chikungunya o morbillo e dati longitudinali derivanti da persone riesposte a varicella e parvovirus B19. Il presente studio porterà a una miglior comprensione dello sviluppo del sistema immunitario e del funzionamento delle malattie infettive.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
2000 Antwerpen
Belgio