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minimal-phagocyte SIGNED

Reconstitution of the basic molecular mechanism of phagocytosis – a bottom-up synthetic biology approach

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 minimal-phagocyte project word cloud

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cutting    ultimately    polymerisation    cellular    cortex    2020    deforms    objects    gap    engulfment    receptors    creation    little    microorganisms    molecular    vesicles    always    innovation    protocells    innate    horizon    edge    line    giant    mobility    functions    artificial    drivers    nevertheless    answer    closure    thereby    cells    reconstitute    tissue    guvs    biotechnologies    sufficient    cues    affinity    engulf    reorganisation    wrap    biology    signalling    players    requiring    immunity    individual    era    biophysics    particle    internalised    reshapes    dynamic    synthetic    questions    wrapping    phagocyte    invading    cell    ant    biophysical    unilamellar    supporting    ing    basis    minimal    abscission    basic    cup    net    spatial    render    cytoskeleton    drug    phagocytic    initiation    components    binding    process    phagocytosis    directed    actin    biotechnological    apoptotic    membrane    model    fill    remodelling    erasynbio   

Project "minimal-phagocyte" data sheet

The following table provides information about the project.

Coordinator
MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV 

Organization address
address: HOFGARTENSTRASSE 8
city: Munich
postcode: 80539
website: www.mpg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 159˙460 €
 EC max contribution 159˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2018-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (Munich) coordinator 159˙460.00

Map

 Project objective

The ability of cells to engulf large objects, such as invading microorganisms or apoptotic cells, is crucial to innate immunity and tissue remodelling. The molecular basis of this process - phagocytosis - is complex, involving numerous receptors and signalling pathways. Nevertheless, the biophysical process is always the same: the cell membrane deforms and reshapes to wrap around the particle, and upon closure and abscission of the resultant cup, the particle is internalised. Although the key molecular players in individual phagocytic pathways have been identified, we still know very little about the basic biophysics common to all phagocytic pathways. I propose to fill this gap in our knowledge by creating a “minimal phagocyte”: I aim to reconstitute a minimal, dynamic actin cytoskeleton and artificial phagocytic receptors in giant unilamellar vesicles (GUVs), thereby identifying the molecular components that are not only necessary but also sufficient for phagocytosis. Using synthetic biology to build a bottom-up model of phagocytosis should answer many open questions, including: are spatial cues resulting from particle binding required for membrane wrapping around the particle? Is directed initiation of actin polymerisation sufficient to render GUVs capable of phagocytosis? What is the role of the membrane-supporting actin cortex and how does the affinity of the receptors affect the engulfment process? Beyond phagocytosis, the minimal-model approach I propose will also be useful to study other cellular functions requiring actin-driven membrane reorganisation, such as cell mobility. In line with the objectives set by ERA-NET ERASynBio and the Horizon 2020 work programme (which identified synthetic biology as one of the “cutting-edge biotechnologies as future innovation drivers”), the creation of “protocells” will not only enhance our understanding of biology, but ultimately also result in novel biotechnological applications, such as improved drug delivery systems.

 Publications

year authors and title journal last update
List of publications.
2018 Thomas Litschel, Kristina A Ganzinger, Torgeir Movinkel, Michael Heymann, Tom Robinson, Hannes Mutschler, Petra Schwille
Freeze-thaw cycles induce content exchange between cell-sized lipid vesicles
published pages: 55008, ISSN: 1367-2630, DOI: 10.1088/1367-2630/aabb96
New Journal of Physics 20/5 2019-06-13

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