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Lipid flippases - Protein-mediated lipid translocation Regulation and physiological significance of transbilayer lipid distribution

Lipid flippases - Protein-mediated lipid translocation Regulation and physiological significance of transbilayer lipid distribution

Objective

The dynamics of biomembrane lipid organisation and its physiological role is a rapidly developing interdisciplinary field. Membrane dynamics is largely controlled by lipid transporters also known as flippases, which play a pivotal role in cell homeostasis. Putative flippases belong to various subfamilies of the P-type ATPases and ATP-binding cassette (ABC) transporters. These proteins are involved in regulating lipid asymmetry, cellular signalling, in the budding of transport vesicles and protein synthesis. Dysfunction of flippases causes severe diseases like cholestasis, atherosclerosis, visual impairment, what emphasises their crucial physiological function. Although these proteins have been connected with the translocation of various classes of membrane lipids across cellular membranes, biochemical and genetic proof of their function and the key features of their activity remain to be elucidated. The network teaming 12 groups is aimed at undertaking an interdisciplinary effort to reveal the molecular identity and cellular localisation of flippases, their three-dimensional structure, substrate specificity, the molecular mechanism, energetics and regulation of their functioning, as well as unraveling the consequences of their action for cell and body physiology. Biophysical approaches will be used to address lipid transport energetics and its role in membrane budding, fission and fusion. The teams have complementary expertise at the highest standard in all required techniques of molecular and cell biology, biochemistry, proteomics, structural biology including X-ray crystal analysis and cryoelectron microscopy, and theoretical and experimental biophysics. In addition to providing novel applicative insights into flippase-related diseases, this project will identify potential targets for designed drug development in pharmaceutics, and will offer new biotechnological tools to use cellular model systems in production of e.g. lipophilic drugs and probiotic food.

Coordinator

HUMBOLDT UNIVERSIT??T ZU BERLIN

Address

Unter Den Linden 6
Berlin

Germany

Administrative Contact

Andreas HERRMANN (Professor)

Participants (11)

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THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

UNIVERSIT??T STUTTGART

Germany

CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

Spain

MEDIZINISCHE UNIVERSIT??T WIEN

Austria

DEN KONGELIGE VETERINAER- OG LANDBOHOEJSKOLE

Denmark

UNIVERSITEIT UTRECHT

Netherlands

INSTITUTE OF ENZYMOLOGY, HUNGARIAN ACADEMY OF SCIENCES

Hungary

TEL AVIV UNIVERSITY

Israel

UNIVERSITY OF COPENHAGEN

Denmark

SWISS FEDERAL INSTITUTE OF TECHNOLOGY ZURICH

Switzerland

Project information

Grant agreement ID: 5330

  • Start date

    1 January 2005

  • End date

    31 December 2008

Funded under:

FP6-MOBILITY

Coordinated by:

HUMBOLDT UNIVERSIT??T ZU BERLIN

Germany