Description du projet
La taille des cellules influence-t-elle le vieillissement?
Le maintien de la taille des cellules est essentiel au bon fonctionnement cellulaire et est étroitement régulé chez les organismes vivants. Les cellules disposent de mécanismes spécifiques permettant de contrôler leur taille et de veiller à ce qu’elles conservent certaines dimensions optimales pour leurs fonctions. Financé par le Conseil européen de la recherche, le projet StemCellSize soumet l’hypothèse qu’une modification de la taille des cellules souches peut être liée au vieillissement. Dans ce contexte, les chercheurs étudieront comment l’hypertrophie cellulaire des cellules souches au cours du vieillissement peut mener à un dysfonctionnement et au développement d’un cancer. Les travaux porteront sur les cellules souches hématopoïétiques et leur relation taille-fonctionnement durant le vieillissement, et feront la lumière sur un sujet jusqu’à présent ignoré.
Objectif
The failure to regenerate tissue underlies a challenging health issue in elderly. A main contributor to this decline is the loss of stem cell function during aging. Despite the essential role of stem cells, it is unclear how they fail to maintain their functions during aging and disease. I discovered a new aspect of stem cell aging in vivo: cellular enlargement. With age, stem cells increase in size leading to their functional decline. However, it is unclear how size impacts stem cell fitness. Moreover, the physiological importance of this process remains unsolved.
My team at the University of Helsinki will address these questions by: (1) identifying pathways that promote stem cell dysfunction during enlargement, (2) assessing the effects of size reduction on stem cell rejuvenation, and (3) illuminating the effects of stem cell size on cancer.
Supported by preliminary data, I hypothesize that cell size is a driver of stem cell aging and cancer. Using hematopoietic stem cells (HSCs) of mouse models, I will identify the molecular mechanisms impairing fitness of large HSCs. I will also perform a screen to identify pathways that modulate the size of HSCs to test for rejuvenation. These will allow me to establish how HSC size affects other cellular aging pathways, organismal health and whether this relationship is causal or correlative. I hypothesize that cellular size impacts HSCs to transform into cancerous cells. To test this, I will use differently sized, oncogenic HSCs from mice and humans to test their potential to facilitate leukemia in vivo and to investigate the underlying mechanisms of this process.
The novel concepts outlined here have exceptional potential for scientific impact as they add a new paradigm to stem cell aging, provide transformative treatment perspectives and examine cancer from a new dimension.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
00014 Helsingin Yliopisto
Finlande