Gene regulatory switches

The control units of developmental episodes are transcription factors and their cis-regulatory elements capable of integrating developmental signals. They form evolutionary conserved building blocks for animal development and, when misregulated, are often involved in human disease including various forms of cancer.

Particularly interesting are transcription factors capable of switching between transcriptional activation and repression that allows binary cell fate choice upon cell division. Notably, repressive function could add regulative possibilities such as repression checkpoints or developmental pausing for diversification of cell fate.

We have observed novel switching events at the level of three transcription factor families (ETS, GATA and TCF) crucially involved in neuro-ectodermal patterning in ascidians.

The ascidian pluripotent ectoderm is particularly suitable to study transcriptional switching mechanisms in vivo since binary events for building precursors of mesendoderm vs. ectoderm, or epidermal vs. neural and/or neurosensorial cells can be followed at cellular resolution. Furthermore, the precicely spaced and timed activation of direct target genes of above transcription factors and knowledge of corresponding regulatory regions provides an entry point for deciphering the regulatory switching behaviour as activators or repressors.

We use the simplicity of Ciona intestinalis (genomic non-redundancy, fixed lineage and electroporation technique) to learn in depth about the funtions of these evolutionary conserved molecules in vivo, and especially about their less analysed, partially novel role as cell fate switches.

The topic of Wnt/ß-cat/Tcf repression (‘opposite signaling’) was subject of the PhD thesis by Willi Kari (ÖAW, TWF and UIBK funding) and Ets switching of the master thesis by Johannes Will and the PhD of Alessandro Pennati.

Early collaborations involved Patrick Lemaire 's lab at IBDM, Marseille, France (now CRBM, Montpellier), Mike Gilchrist, Crick Institute London, UK and  Daniel Sobral, Portugal (see publications up to 2015). Subsequent interactions include the labs of Vincent Bertrand, IBDM, France, and Yutaka Satou, Kyoto, Japan, on novel aspects of TCF function, the Yasuo/Hudson lab in Villefranche sur Mer, France, on FGF/Ets signaling, Seb Shimeld, UK, on gene regulation of sensory cells and Loriano Ballarin, Padova, Italy, on tunicate blood cells. Interactions within the UIBK Doctoral Schools AgeReg and ARDRE include the Hobmayer, Edenhofer, Jansen-Dürr and Zwerschke labs, and other members of the CMBI. We were involved in the EU-COST action CA16203 MARISTEM and co-organized an online training school and an educational movie. 

Ascidian bioadhesion

Freeswimming ascidian larvae produce adhesives when settling at the beginning of metamorphosis to form sessile adults. Consequently, ascidians form invasive species and are major biofoulers threatening marine shipping and food industries.

To define their adhesive properties we describe the ascidian larval adhesive organs and integrate knowledge about its stepwise building from neurectoderm in molecular terms. We isolate candidate genes by transcriptomics, proteomics and functional genomics and test their role in adhesive organ formation and adhesive production. Our research may contribute to the design of both, industrial anti-fouling reagents and, medically relevant tissue compatible glues.

This topic is subject to the PhD thesis of Fan Zeng (UIBK and ÖAW funding, UIBK Doctoral School AgeReg) and was funded by UIBK, EU-Assemble-Plus (2020) and the ongoing FWF project ‘TuniGlue’.

Collaborations are ongoing locally, within the Zoology at UIBK, with the teams of Peter Ladurner (co-supervision of PhD student Julia Wunderer, funding Südtiroler Stipendium, TWF, UIBK), Willi Salvenmoser and Anna Seybold (Electron Microscopy, EM) and at the Innsbruck Medical University  (MUI) with Michael Hess (HPF-EM), Markus Lindner and Bettina Sarg, MUI (Proteomics). International collaborations are with Daniel Sobral, Portugal (differential transcriptomics), Roberta Pennati, Milan, Italy and Stefano Tiozzo, Villefranche-sur-mer, France (ascidian species) and Alberto Stolfi, Georgia Tech, USA (papillar cell types and scRNAseq). We participated in the EU-COSTActionsTD0906 and CA15216 on Bioadhesion and in the EU Management Committee for Austria since 2017. A COST action Training school was held at UIBK in September 2017.

Members of this workgroup are

• Ute Rothbächer (head)
• Fan ZENG, PhD, postdoc
• Alessandro Pennati, PhD
• Matthias Achrainer, PhD candidate
• Luca Ciampa, master student
• lukas Walser, Master student
• Michell Illiana Chimal Calderón, Bachelor student
• Klára Faschingbauerová, Bachelor student
• Timothy Prohl, Hamburg School of Life Science, Erasmus Taining and Education

  Alumni:

  Willi Kari, PhD
  Johannes Will, MSc
  Barbara Ritter, MSc
  Milos Jakobi, MSc