Intermediate filaments are major components of the cytoskeleton acting as mechanical stabilizers and as modulators of cellular differentiation and proliferation. The molecular mechanisms, which regulate intermediate filament dynamics and their 3D architecture in a true tissue context, have not been elucidated. To do this, we use the model organism Caenorhabditis elegans. With the help of transgenic strains we have performed a chemical mutagenesis screen and isolated mutants with altered intermediate filament organization. The goal of the current project is to characterize these mutants and to isolate further mutants in order to work out the molecular pathways that determine intermediate filament network dynamics. We also want to find out how the specific intermediate filament network architecture contributes to intestinal cell polarity and function. The expected results will be of fundamental importance for the understanding of the cytoplasmic intermediate filament cytoskeleton and its alterations in the context of epithelial differentiation and its manifold disturbances.
- Working with the model organism Caenorhabditis elegans including its genetical manipulation (either targeted via Crispr or using chemical mutagenesis)
- Mechanical, microbial, osmotic and oxidative stress assays
- Experience with Lightsheet and Apotome microscopy
The intestinal intermediate filament network responds to and protects against microbial insults and toxins.
Geisler F, Coch RA, Richardson C, Goldberg M, Denecke B, Bossinger O, Leube RE.
Development. 2019 Jan 23;146(2). pii: dev169482. doi: 10.1242/dev.169482.
A novel function for the MAP kinase SMA-5 in intestinal tube stability.
Geisler F, Gerhardus H, Carberry K, Davis W, Jorgensen E, Richardson C, Bossinger O, Leube RE.
Mol Biol Cell. 2016 Dec 1;27(24):3855-3868. Epub 2016 Oct 12.
Epithelial Intermediate Filaments: Guardians against Microbial Infection?
Geisler F, Leube RE.
Cells. 2016 Jun 27;5(3). pii: E29. doi: 10.3390/cells5030029. Review.
The novel intestinal filament organizer IFO-1 contributes to epithelial integrity in concert with ERM-1 and DLG-1.
Carberry K, Wiesenfahrt T, Geisler F, Stöcker S, Gerhardus H, Überbach D, Davis W, Jorgensen E, Leube RE, Bossinger O.
Development. 2012 May;139(10):1851-62. doi: 10.1242/dev.075788.