Deliverables
Analysis of Axin1, Axin2, and APC roles in liver and intestinal cell division involves a) cell-biological analysis of Axin1, Axin2, and APC null phenotypes in liver and intestinal cell division, and b) Mechanistic analysis of links between altered G2/M mitotic programme and increased cell division following Axin loss.
Quantitative analyses of local polarity perturbations on polarized growth will involve a) generation of strains which can generate locally increased concentrations of PS, PIP2, activated Cdc42 and activated Rho1, b) Quantitative analyses of local perturbation of PS, PIP2, activated Cdc42 and activated Rho1 levels on external mediated polarized growth and force generation.
Analysis of cell contact dependent transmission of Wnt-signal in seam cell PCP involves a) C. elegans clonal analysis of lineage-specific knock out mutants, b) analysis of cell-cell contact dependent transmission of the Wnt-signal in seam cell PCP, and c) identification of components critical for mitotic spindle and cleavage plane positioning.
Biochemical characterization of the Scrib polarity complex will involve a) identification of new partners of the mammalian polarity protein Scrib, b) biochemical characterization of the Scrib polarity complex in migrating cells and polarized epithelial cells, and c) characterization of the polarity function of Scrib partners in migrating cells and polarized epithelial cells.
Semi-automated culturing of organoids in a bioreactor involves a) determining the correlation between processing conditions and organoid morphology and function, and b) bespoke hollow fibre bioreactor design for processing of organoids.
Elucidating the mechanistic role of microtubules in polarization of 3D-cultured epithelial cells involves a) quantitative description of the role of microtubule-attachment complexes in cortical polarization in 3D breast epithelia acini and their modification during EMT and invasive growth in 3D, b) characterization of the biochemical connection between microtubule attachment complexes and the Scrib complex, c) quantitative characterization of the role of microtubule dynamics in polarity maintenance in 3D-cultured epithelial cells and the effects of microtubule-targeting agents on this process.
Characterizing the role of phosphoinositides in control of cell polarity during collective migration will involve a) characterization of phosphoinositide distribution during collective migration, b) characterisation of the role of phosphoinositides and more precisely of the lipid phosphatase PTEN in the control of cell polarity during collective migration, c) identification of signalling cascades controlled downstream of phosphoinositide signalling, and d) elucidation of the consequences of PTEN loss of functions in tumor spreading.
1. Development of a mechanochemical model of PAR polarity patterning will involve a) simultaneous and complete midplane concentration and flowfields of markers of polarity and the actomyosin cortex under wild type and RNAi conditions, b) Identication of which markers of polarity control what activities of the cellular cytoskeleton, c) Development of a quantitative and predictive description of PAR polarity as a process of mechanochemical patterning formation in a regulated thin film active fluid.
Developing a comprehensive, quantitative mathematical description of PAR polarity will involve a) Defining mobility parameters for PAR network components, including diffusion coefficients and membrane association/dissociation rates, b) Defining binding parameters governing pairwise interactions between PAR com-ponents. c) Construction and analysis of a model of PAR polarity based on parameters in (a) and (b) to identify core design principles of PAR network.
Developing a computational model of epithelial regeneration after wounding involves a) live imaging of Drosophila wing disc regeneration and polarity re-establishment, b) quantification of changes in tissue mechanics after the wound and during the regeneration process, and c) building of a computational model of epithelial regeneration.
Elucidation of GTPase-regulator circuits essential for yeast and C. elegans polarity will involve a) identification of GTPase-regulator circuits essential for polarized growth in yeast and polarity establishment and maintenance in C. elegans early embryos, b) characterization of the role of Arf/Rab GTPases in epithelial polarity and tissue organization, and c) generation of a number of C. elegans strains expressing GFP or mCherry tagged Arf and Rab GTPases and their effectors, and generation of specific point mutations therein using the CRISPR-Cas9 system.
Characterization of PAR, Crumbs and Scribble in C. elegans larval epithelia will involve a) generation of genetic null alleles of members of the Par, Crumbs, and Scribble complexes for which such alleles do not exist yet, and b) analysis of inactivation of members of these complexes on polarity in the intestine and seam cells.
Review article by the ESRs incorporating data obtained by PolarNet
Analysis of the mechanisms that maintain tissue integrity in seam epithelium involves a) generation of strains in which apical-basal polarity, cell adhesion, tissue polarity, and various tumour suppressors can be disrupted specifically in the seam epithelium, and b) analysis of genetic interactions between these regulators, with the goal of causing seam cells to leave the epithelium.
compulsory deliverable
compulsory deliverable
Elucidating the mechanisms of mechanotransduction during division in epithelial tissue involves a) integrated understanding of cytokinesis in epithelial tissue, b) uncovering the mechanisms of mechanotrandsuction during division in epithelial tissue, and c) force measurements in whole animal.
Super-resolution localization of polarity regulators at the plasma membrane will involve a) immunization of llama's with MDCK cells to generate a MDCK-immune library, b) production and purification of the membrane anchoring component for selection of specific nanobodies, c) selection and characterization of nanobodies binding to anchoring proteins, d) imaging of membrane anchoring of the spindle in 3D by super-resolution microscopy of 2D MDCK cell cultures, and e) quantitative characterization of the organization of the spindle orientation by anchoring complexes and the effect of EGF thereon.
Video highlighting importance of polarity for website & youtube
Summaries of ESRs results placed on website by the ESRs
Bi-weekly ‘Polarizing Cells’ blog entry on website
Web presence established.
Closing symposium
compulsory deliverable
Network Summer School
Network Symposium
Network symposium
All ESR are evaluated by the Supervisory Board for eligibility to apply for a Doctorate degree.
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Publications
Author(s): Benjamin P Bouchet, Rosemarie E Gough, York-Christoph Ammon, Dieudonnée van de Willige, Harm Post, Guillaume Jacquemet, AF Maarten Altelaar, Albert JR Heck, Benjamin T Goult, Anna Akhmanova
Published in: eLife, Issue 5, 2016, ISSN 2050-084X
DOI: 10.7554/eLife.18124
Author(s): Benjamin P. Bouchet, Ivar Noordstra, Miranda van Amersfoort, Eugene A. Katrukha, York-Christoph Ammon, Natalie D. ter Hoeve, Louis Hodgson, Marileen Dogterom, Patrick W.B. Derksen, Anna Akhmanova
Published in: Developmental Cell, Issue 39/6, 2016, Page(s) 708-723, ISSN 1534-5807
DOI: 10.1016/j.devcel.2016.11.009
Author(s): Jacob D. Reich, Lars Hubatsch, Rukshala Illukkumbura, Florent Peglion, Tom Bland, Nisha Hirani, Nathan W. Goehring
Published in: Current Biology, Issue 29/12, 2019, Page(s) 1911-1923.e5, ISSN 0960-9822
DOI: 10.1016/j.cub.2019.04.058
Author(s): Nisha Hirani, Rukshala Illukkumbura, Tom Bland, Grégoire Mathonnet, Delphine Suhner, Anne-Cecile Reymann, Nathan W. Goehring
Published in: Journal of Cell Science, Issue 132/14, 2019, Page(s) jcs230714, ISSN 0021-9533
DOI: 10.1242/jcs.230714
Author(s): Rukshala Illukkumbura, Tom Bland, Nathan W. Goehring
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 123-134, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.10.005
Author(s): Eider Valle-Encinas, Trevor C. Dale
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 17-25, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.07.014
Author(s): Chiara De Pascalis, Carlos Pérez-González, Shailaja Seetharaman, Batiste Boëda, Benoit Vianay, Mithila Burute, Cécile Leduc, Nicolas Borghi, Xavier Trepat, Sandrine Etienne-Manneville
Published in: The Journal of Cell Biology, Issue 217/9, 2018, Page(s) 3031-3044, ISSN 0021-9525
DOI: 10.1083/jcb.201801162
Author(s): Lars Hubatsch, Florent Peglion, Jacob D. Reich, Nelio T. L. Rodrigues, Nisha Hirani, Rukshala Illukkumbura, Nathan W. Goehring
Published in: Nature Physics, Issue 15/10, 2019, Page(s) 1078-1085, ISSN 1745-2473
DOI: 10.1038/s41567-019-0601-x
Author(s): Bertille Bance, Shailaja Seetharaman, Cécile Leduc, Batiste Boëda, Sandrine Etienne-Manneville
Published in: Journal of Cell Science, Issue 132/7, 2019, Page(s) jcs225805, ISSN 0021-9533
DOI: 10.1242/jcs.225805
Author(s): Shailaja Seetharaman, Sandrine Etienne-Manneville
Published in: Journal of Cell Science, Issue 132/19, 2019, Page(s) jcs232843, ISSN 0021-9533
DOI: 10.1242/jcs.232843
Author(s): Eric Victor van Leen, Florencia di Pietro, Yohanns Bellaïche
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 9-16, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.07.013
Author(s): Patrícia M. Silva, Charles Puerner, Agnese Seminara, Martine Bassilana, Robert A. Arkowitz
Published in: Cell Reports, Issue 28/8, 2019, Page(s) 2231-2245.e5, ISSN 2211-1247
DOI: 10.1016/j.celrep.2019.07.062
Author(s): Nathan Jespersen, Aidan Estelle, Nathan Waugh, Norman E Davey, Cecilia Blikstad, York-Christoph Ammon, Anna Akhmanova, Ylva Ivarsson, David A Hendrix, Elisar Barbar
Published in: Life Science Alliance, Issue 2/4, 2019, Page(s) e201900366, ISSN 2575-1077
DOI: 10.26508/lsa.201900366
Author(s): Miao Yu, Shimin Le, York-Christoph Ammon, Benjamin T. Goult, Anna Akhmanova, Jie Yan
Published in: Nano Letters, Issue 19/9, 2019, Page(s) 5982-5990, ISSN 1530-6984
DOI: 10.1021/acs.nanolett.9b01732
Author(s): Eric C. Arakel, Martina Huranova, Alejandro F. Estrada, E-Ming Rau, Anne Spang, Blanche Schwappach
Published in: Journal of Cell Science, Issue 132/16, 2019, Page(s) jcs232124, ISSN 0021-9533
DOI: 10.1242/jcs.232124
Author(s): Amalia Riga, Victoria G Castiglioni, Mike Boxem
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 1-8, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.07.017
Author(s): Yamini Ravichandran, Bruno Goud, Jean-Baptiste Manneville
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 104-113, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.10.003
Author(s): Lavinia Capuana, Astrid Boström, Sandrine Etienne-Manneville
Published in: Current Opinion in Cell Biology, Issue 62, 2020, Page(s) 114-122, ISSN 0955-0674
DOI: 10.1016/j.ceb.2019.10.001
Author(s): Suzanne E. M. van der Horst, Janine Cravo, Alison Woollard, Juliane Teapal, Sander van den Heuvel
Published in: Development, Issue 146/22, 2019, Page(s) dev180034, ISSN 0950-1991
DOI: 10.1242/dev.180034
