Molecular and biophysical drivers of epithelial cell density and cell competition.

Jody Rosenblatt (primary)
King’s College London
King's College London
Guillaume Charras (secondary)
London Centre for Nanotechnology
University College London

Abstract

Epithelial cells perform most functions of each organ while protecting them from the outside environment. Intrinsic to these functions is maintaining a proper density, yet this varies between organs and becomes misregulated in diseases like cancer. Here, we examine what controls cell number density and if this same mechanism controls cell competition, or removal of unfit cells within an epithelium. This project will take a combined approach using live imaging of cell culture lines that grow to different densities, alone, or in co-culture, and in silico simulations to confine models.


References

1 Eisenhoffer GT, Loftus PD, Yoshigi M, Otsuna H, Chien CB, Morcos PA, Rosenblatt J (2012). Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature, 484(7395), 546-9.
2 Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K, Davey CF, Krishnegowda V, Rosenblatt J. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature. 2017 Mar 2;543(7643):118-121. PubMed PMID: 28199303; PubMed Central PMCID: PMC5334365.
3 Eisenhoffer GT, Rosenblatt J (2013). Bringing balance by force: live cell extrusion controls epithelial cell numbers. [Review]. Trends Cell Biol, 23(4), 185-92.
4 Bove A, Gradeci D, Fujita Y, Banerjee S*, Charras G*, Lowe A*. “Local cellular neighbourhood controls proliferation in cell competition”. Mol Biol Cell, 28(23):3215-3228, (2017).*
5 Kuipers D, Mehonic A, Kajita M, Peter L, Fujita Y, Duke T, Charras G*, Gale J*. “Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours”, J Cell Sci, 127(Pt 6):1229-41, (2014).


BBSRC Area
Animal disease, health and welfare
Area of Biology
Cell BiologyPhysiology
Techniques & Approaches
BiochemistryBiophysicsGeneticsImage ProcessingMathematics / StatisticsMolecular Biology