Lipid rafts and membrane curvature: Hubs of intracellular signalling
Name of applicant
Lasse Hyldgaard Klausen
Amount
DKK 350,000
Year
2018
Type of grant
Internationalisation Fellowships
What?
Signalling to and from cells is initiated by membrane receptors concentrated in specific regions of the cellular membrane. These regions possess unique chemical and physical properties such as increased rigidity, strong curvature and concentrated surface charge. In this project I will investigates two such types of nanoscale regions of interest: Lipid rafts and locally curved membranes. Microscopic effects of charge distribution will be investigated using model membranes, while curvature effects will be characterised using both model membranes and live cells.
Why?
The lipid raft hypothesis has had a significant impact on cell biology research, being attributed to explaining drug resistance in cancer cells, escape hatches for viruses such as the ones that cause flu, and the activation of the T cell receptor. Despite this, the existence of lipid rafts has been repeatedly questioned due to technical challenges in studying the sub-microscopic and dynamic rafts in the membranes of living cells. Providing new data to improve the lipid raft model and the link to membrane curvature could ultimately lead to a better understanding of cell signalling.
How?
Model membrane techniques will be used to characterise microscopic effects of charge distribution on the membrane using a recently developed method, the quantitative surface charge microscope (QSCM). A new nanocurvature platform developed at Stanford University will then be used to culture cells transfected to express the curvature sensitive proteins Dynamin2 and FBP17 coupled to fluorescent markers. The proteins will finally be purified and their inherent curvature sensitivity tested in respect to membrane charge and curvature.