The Project
Systems analysis of caveolae- and lipid raft-mediated endocytosis in multicellular physiology.
Winner
Lucas Pelkmans
ETH Zurich
Institute for Molecular Systems Biology
Zürich, Switzerland
http://www.biotech.biol.ethz.ch/
Dutchman Lucas Pelkmans, 30 years old, graduated from the University of Utrecht, The Netherlands, in 1999 as a Master of Science in Medical Biology with two majors (cum laude). He then joined the Swiss Federal Institute of Technology in Zürich, Switzerland. Institute of Biochemistry, to complete his Ph.D. thesis for which he won the ETH silver medal. He was a postdoctoral fellow at the Institute, and joined the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, Germany, in 2003.
Award
€1,199,196
Project Description
Internalization of caveolae(*) and lipid rafts, and trafficking through a new type of endocytic organelle, the caveosome, comprises a new endocytic pathway that was recently discovered in my previous work. It is clear that caveolae and their coat protein Caveolin-1 are involved in growth factor receptor signalling, integrin signalling and cell adhesion, it has been suggested that Caveolin-1 has tumour suppressor activity and Caveolin-1 null mice show severe fibrosis in several tissues. In all cases however, it is not understood how the caveolae-mediated endocytosis is involved.
This project will address these questions by first obtaining a comprehensive, systems view on caveolae- and lipid raft mediated endocytosis, using a combination of functional genomics, multidimensional time-lapse microscopy with high temporal and structural resolution for the analysis of the systems characteristics, and mathematical modelling.
Next, the technology, models and concepts developed will be used to address, in molecular detail, how these endocytic pathways regulate cell adhesion, anchorage-dependent cell growth and remodelling of the extracellular matrix in tissue culture cells and in endothelial cells and fibroblasts during angiogenesis and connective tissue formation in situ in D. rerio.
Finally, a model for tumour metastasis in D. rerio will be developed and used to study the molecular dynamics of caveolae- and lipid raft mediated-endocytosis during tumour metastasis, to understand how these pathways are altered, and how this leads to abberant cell adhesion and anchorage-dependent cell growth, and to remodelling of the extra-cellular matrix.
(*) Definition - Caveolae:
In biology, caveolae (Latin for little caves) are small invaginations of the plasma membrane in many cell types, especially in endothelial cells. Some cell types, like neurons, completely lack caveolae. These flask-shaped structures are rich in proteins and lipids and are used for several functions in signal transduction. They are also believed to play a role in endocytosis, oncogenesis, and the uptake of pathogenic bacteria. The formation and maintenance of caveolae is primarily due to the protein caveolin. (Source: Wikipedia)
