Project description
Physiological significance of cell membrane asymmetry
The living cell membrane inter-leaflet lipid bilayer asymmetry requires energy for establishing and maintaining, but the physiological role of bilayer lipids during dynamic cellular processes remains poorly understood. The EU-funded nano-Asymmetry project aims to overcome previous technological limitations and develop a method to directly visualise and quantify membrane asymmetry, applicable to analyse any cell membranes, including the intracellular. The study will combine super-resolution microscopy with state of-the-art isotropic expansion methods to visualise lipids in the individual leaflets. The analysis of the lipid asymmetry perturbations induced by infection with viral particles will provide information about the physiological significance of bilayer asymmetry. The novel methodology will help to understand membrane asymmetry’s impact on cellular physiology and disease mechanisms.
Objective
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.
Fields of science
Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
17177 Stockholm
Sweden