Project description DEENESFRITPL Ageing: does cell size matter? Cell size maintenance is crucial for proper cellular function and is tightly regulated in living organisms. Cells have specific mechanisms to control their size, ensuring they stay within certain dimensions optimal for their functions. Funded by the European Research Council, the StemCellSize project proposes the hypothesis that a change in stem cell size may be linked to ageing. To delineate this, researchers will study how cellular enlargement in stem cells during ageing can lead to dysfunction and the development of cancer. The work will focus on haematopoietic stem cells and their size-fitness relationship during ageing, shedding light on a previously unexplored topic. Show the project objective Hide the project objective Objective 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. Fields of science medical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologyleukemia Keywords cell size hematopoietic stem cells metabolism leukemia Programme(s) HORIZON.1.1 - European Research Council (ERC) Main Programme Topic(s) ERC-2023-STG - ERC STARTING GRANTS Call for proposal ERC-2023-STG See other projects for this call Funding Scheme HORIZON-ERC - HORIZON ERC Grants Host institution HELSINGIN YLIOPISTO Net EU contribution € 1 500 000,00 Address YLIOPISTONKATU 3 00014 Helsingin Yliopisto Finland See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all HELSINGIN YLIOPISTO Finland Net EU contribution € 1 500 000,00 Address YLIOPISTONKATU 3 00014 Helsingin Yliopisto See on map Region Manner-Suomi Helsinki-Uusimaa Helsinki-Uusimaa Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 1 500 000,00
