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Membrane partitioning of homologous proteins

Objective

My goal is to elucidate how structurally closely-related proteins are selectively partitioned in distinct membrane domains that allow localization, clustering and segregation of specific cellular activities. Although many of the mechanisms that govern membrane organization are increasingly well understood, such as lipid ‘rafts’ or protein-anchoring to the cortical cytoskeleton, these mechanisms are not sufficiently specific to account for the partitioning of closely homologous proteins in separate membrane domains. I believe that the observed highly selective membrane partitioning can only be explained by the combined action of protein-protein and protein-lipid interactions and thermodynamic properties of the membrane (length, charge, degree of hydrophobicity). I aim to gain a full understanding of how homologous proteins partition in distinct functional membrane domains by studying SNARE proteins as a model system. Different SNAREs partition in different domains with different degrees of overlap in the plasma membrane where they catalyze the final membrane fusion steps of various exocytotic pathways. I will employ quantitative super-resolution microscopy to study the effects of selective (biochemical and genetic) perturbations on SNARE partitioning in both precisely controllable artificial membranes and in PC12 cells. This will allow me to elucidate the mechanisms, contributions and interplay of individual membrane clustering mechanisms in SNARE domain organization. I then plan to demonstrate that the mechanisms of SNARE partitioning explain the membrane organization of other (homologous) proteins as well. My ultimate ambitious goal is to generate a complete model of how proteins are organized in biological membranes. I anticipate that my findings will uncover new and general mechanisms of membrane organization and, since membranes are involved in almost all cellular processes, my work may have impact on virtually all areas of the health and life sciences.

Principal Investigator

Geert Van Den Bogaart (Dr.)

Host institution

STICHTING KATHOLIEKE UNIVERSITEIT

Address

Geert Grooteplein Noord 9
6525 Ez Nijmegen

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 500 000

Principal Investigator

Geert Van Den Bogaart (Dr.)

Administrative Contact

Wim Van Oijen (Mr.)

Beneficiaries (1)

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STICHTING KATHOLIEKE UNIVERSITEIT

Netherlands

EU Contribution

€ 1 500 000

Project information

Grant agreement ID: 336479

Status

Closed project

  • Start date

    1 December 2013

  • End date

    30 November 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

STICHTING KATHOLIEKE UNIVERSITEIT

Netherlands