Description du projet
Importance physiologique de l’asymétrie de la membrane cellulaire
L’asymétrie de la bicouche lipidique intercalaire de la membrane des cellules vivantes requiert de l’énergie pour s’établir et se maintenir, mais le rôle physiologique des lipides de la bicouche au cours des processus cellulaires dynamiques demeure mal compris. Le projet nano-Asymmetry, financé par l’UE, entend surmonter les limitations technologiques antérieures et développer une méthode permettant de visualiser et de quantifier directement l’asymétrie des membranes, applicable à l’analyse de toutes les membranes cellulaires, y compris intracellulaires. L’étude combinera la microscopie à super-résolution avec des méthodes d’expansion isotrope de pointe pour visualiser les lipides dans les feuillets individuels. L’analyse des perturbations de l’asymétrie des lipides induites par l’infection par des particules virales fournira des informations sur l’importance physiologique de l’asymétrie des bicouches. Cette nouvelle méthodologie aidera à comprendre l’impact de l’asymétrie membranaire sur la physiologie cellulaire et les mécanismes des maladies.
Objectif
The compositional and structural asymmetry of cell membranes remains one of the greatest knowledge gaps in cell biology. Cells invest significant amount of energy to establish and maintain inter-leaflet asymmetry; however, the physiological roles of bilayer lipids during dynamic cellular processes in eukaryote membranes remain poorly understood, mostly due to the limits of previously available methodologies and the complexity of lipid membranes. Current knowledge originates from indirect and perturbing techniques (i.e. enzymatic digestion and mass spectrometry) which significantly limits the applicability to certain cell types with no internal membranes. Moreover, these bulk methods do not provide spatial information on lipid asymmetry which prevents detailed observation of subcellular changes during dynamics processes such as host-pathogen interactions.
In this project, I will develop a method to directly visualize and quantify membrane asymmetry, which will be applicable to study any cell type as well as intracellular membranes. Recent advances in super-resolution microscopy, including my latest publications, paved the way for direct observation and quantification of lipid asymmetry. I will combine state-of-the-art isotropic expansion methods with super-resolution microscopy to visualize membrane lipids in individual leaflets of bilayers. To obtain further insights on the physiological role of membrane asymmetry, I will investigate changes in lipid asymmetry induced by infection with viral particles. The novel methods I will develop will significantly contribute to a better understanding of lipid asymmetry in biological membranes and its impact in cellular physiology and diseases mechanisms.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinateur
17177 Stockholm
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