Descrizione del progetto
La metilazione del DNA come orologio epigenetico negli uccelli selvatici
La metilazione del DNA, un effetto epigenetico, è emersa come marcatore superiore dell’età biologica negli studi epidemiologici, e permette di prevedere la durata della vita residua meglio dell’età cronologica. Pertanto, individuare i fattori che contribuiscono alla metilazione legata all’invecchiamento è divenuto importante per comprendere l’invecchiamento sano. Il progetto wildEPIClock, finanziato dall’UE, sfrutterà un ampio set esistente di campioni biologici di taccole selvatiche (Coloeus monedula) con storie di vita note, monitorate per tutta la loro vita, per rivelare cause e conseguenze della variazione della metilazione del DNA. Il progetto integrerà l’ecologia evolutiva, la genetica quantitativa e la biomedicina per sviluppare un orologio epigenetico al fine di comprendere le variazioni della metilazione del DNA e le loro conseguenze in termini di fitness, svelando i meccanismi extragenici dell’ereditarietà e dell’evoluzione fenotipica in una configurazione ecologicamente rilevante.
Obiettivo
DNA methylation (DNAm), an epigenetic effect, changes with age in a site-dependent way. DNAm score, integrating methylation state at many sites, has recently emerged as a superior marker of biological age in epidemiological studies: it predicts remaining lifespan markedly better than chronological age (CA). Identification of factors that contribute to ageing-related methylation has thereby become of importance for understanding healthy ageing. In this project, I will use a large existing set of biological samples of a free-ranging animal (jackdaw, Coloeus monedula) with known life-histories, monitored longitudinally throughout their lives, to reveal causes (experimental approach) and consequences (lifelong monitoring) of DNAm variation. By integrating expertise from evolutionary ecology, quantitative genetics and biomedicine, I will develop an epigenetic clock to build a comprehensive understanding of shifts in DNAm and their ultimate fitness consequences, unravelling extragenic mechanisms of inheritance and phenotypic evolution in an ecologically relevant setup. Specific objectives, implemented through dedicated work packages, are:
O1-Groundwork: Develop an epigenetic clock of CA for wild jackdaws. Method WP1: wet-lab analyses of DNAm and identification of CpG sites where methylation changes with CA to be combined in a DNAm score of age.
O2-Causes: Identify environmental and quantitative (epi)genetic causes of DNAm variation, leveraging a long-term brood size manipulation experiment that affected ageing in parents (mortality) and offspring (telomere dynamics). Method WP2: analysis of longitudinal age-corrected DNAm data and the pedigree.
O3&O4-Consequences: Study the link between the DNAm and its results on life-history traits according to the manipulation (O3,WP3a). Quantify transgenerational epigenetic inheritance (O4, WP3b). Method: longitudinal data analysis of phenotypic traits and transgenerational effects to unravel consequences of variation in DNAm.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-IF-EF-ST - Standard EFCoordinatore
9712CP Groningen
Paesi Bassi