Objective During mitosis, cells can undergo asymmetric cell division, where daughter cells are endowed with different fates. Asymmetric division enables developing organisms to generate their particular diversity of cell types through a balanced combination of self-renewal and differentiation. Better understanding the mechanisms of asymmetric cell division will shed light on how cell renewal, differentiation and proliferation are controlled. In the longer term, this knowledge might enable regenerating defective cells in ageing and disease, generating cells of a particular identity for therapeutic purposes and tackling cell proliferation in cancer.The fate asymmetry results from a differential distribution of fate determinants between daughter cells. One way this segregation is implemented is through the directional trafficking of vesicles called endosomes along the microtubules of the mitotic spindle. While our understanding of the trafficking step has improved a lot through recent studies, it remains unclear how asymmetrically distributed endosomes at the spindle are ultimately released into the target daughter cell. This proposal aims at identifying the molecular mechanisms underlying this final, decisive step of asymmetric division: endosome departure from the spindle.We will work through four specific aims: 1 Characterise the dynamics of endosome departure under wild-type conditions, 2 Identify molecular interactions triggering departure, 3 Build a mathematical theory of the physics of departure,4 Test whether our proposed model can be generalised to other models of asymmetric division.Recent progress on directional endosomal trafficking has laid strong conceptual and practical frames to now focus on the next step of asymmetric division. Thus the proposed project is timely both through the question it addresses and the tool availability. This project is also intrinsically intersectorial, integrating physics, chemistry and mathematics to address a biological question. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinshumanitiesartsmodern and contemporary artcinematographymedical and health sciencesclinical medicineoncologynatural sciencesmathematicsapplied mathematicsmathematical model Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITE DE GENEVE Net EU contribution € 187 419,60 Address RUE DU GENERAL DUFOUR 24 1211 Geneve Switzerland See on map Region Schweiz/Suisse/Svizzera Région lémanique Genève 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 € 187 419,60