Forschungsbereich Evolutions- und Entwicklungsbiologie
Der Forschungsbereich Evolutions- und Entwicklungsbiologie setzt sich aus folgenden Forschungsgruppen zusammen:
Bioadhesion meets functional genomics in flatworms
Bio-inspired adhesives have the potential establishing the basis for innovative industrial adhesives to be used in biomedicine or for high-tech applications. A broad range of organisms use adhesives to attach to substrates but the nature of these glues is not well understood. Current efforts are aiming to unravel the molecular basis of biological adhesion of diverse organisms. We are investigating free-living flatworms (Platyhelminthes) which are able to adhere and release from the substrate using duo-gland adhesive organs. Our model organism - the free-living flatworm Macrostomum lignano possesses about 130 adhesive organs, which enable the worm to adhere to and release rapidly from the substrate. The adhesive organs consist of three cell types, an adhesive gland cell, a releasing gland cell, and a modified epidermal cell. Based on our knowledge of the morphology and the available molecular biology tools we aim to characterize molecules involved in the adhesion and releasing process. Using comparative transcriptomics in combination with a large-scale in situ hybridization screen, we could so far identify 29 possible adhesion or releasing related transcripts. Further investigations may lead to the finding of a de novo bio-mimicked glue and a corresponding solvent.
Supported by FWF P25404-B25 and COST action TD090
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 switching behaviour for the three transcription factor families (ETS, GATA and TCF) crucially involved in early ectoderm patterning in ascidians.
The ascidian pluripotent ectoderm is particularly suitable to study transcriptional switching mechanisms in vivo as binary events for building precursor of mesendoderm vs. ectoderm, or epidermal vs. neural and/or neurosensorial cells is known with 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.
This topic is subject to a PhD thesis for Willi Kari (ÖAW, TWF and UIBK funding) and a master thesis for Johannes Will. The projects were partially begun in Patrick Lemaire 's lab at IBDM, Marseille, France (now CRBM, Montpellier), collaboration also with Mike Gilchrist, Crick Institute London, UK.
We collaborate with Vincent Bertrand , IBDM, France, and Yutaka Satou , Kyoto, Japan, on novel aspects of TCF function. Interactions within the UIBK Doctoral School AgeReg are planned on this topic with the Hobmayer, Edenhofer, Jansen-Dürr and Zwerschke labs.
Freeswimming ascidian larvae produce adhesives when settling at the beginning of metamorphosis to form sessile adults. Consequently, ascidians 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. We are members of the EU-COSTActionsTD0906 and CA15216 on Bioadhesion and in the EU Management Committee for Austria since 2017.
This topic is subject to a PhD thesis for Fan Zeng (UIBK and ÖAW funding, UIBK Doctoral School AgeReg).
Collaboration with Peter Ladurner, UIBK : co-supervision of PhD student Julia Wunderer (funding Südtiroler Stipendium, TWF, UIBK), MASS-Spec and NGS (Markus Lindner, MUI and ETH Zürich) and Willi Salvenmoser , UIBK. Further collaborations with Daniel Sobral , Gulbenkian Institute, Portugal (differential transcriptomics) and Roberta Pennati , University Milan, Italy. Additional funding: EU-COST ActionsTD0906 and CA15216 Biological adhesives. A COST action Training school was held by us at UIBK in September 2017.
Members of this workgroup are
- Ute Rothbächer (head)
- Fan Zeng (postdoc)
Alessandro Pennati (doctoral candidate)
Hydra’s simple body is composed of three independent cell lineages, all of which contain large pools of either epithelial or small, set aside adult stem cells. They represent ancestral stem cell types present when animal multicellularity evolved. Of particular interest are interstitial stem cells. These stem cells give rise to somatic cell types such as neurons, stinging cells and gland cells and thereby control most of the polyp’s behavior, as well as to both types of gametes. They exhibit a stochastic mode of decision making, whose molecular control mechanisms are unknown. We are interested in characterizing regulatory factors in order to gain a molecular understanding of the homeostatic balance of cell types during growth, regeneration, and sex-induced ageing. Our recent work has focused on Myc proteins, their structural and functional conservation, and their biochemical properties in comparison to mammalian c-Myc. Myc1 and Myc2 act in self renewal in interstitial stem cell, Myc3 seems to be involved in neurogenesis. In addition, we study the role of Wnt/beta-Catenin signaling in stem cell decision making. The accompanying scheme illustrates our current working hypothesis, which we have started to test in detail by functional interference.
Hydra is one of the classic models for regeneration research exhibiting an unparalleled capacity to rebuild lost body parts. Hydra regeneration is a result of exceptional phenotypic and molecular plasticity of the remaining tissue. An extreme case of regeneration is re-aggregation of suspensions of dissociated cells and the following self-organization into intact polyps within days. We were able to show that activation of the Wnt/beta-Catenin pathway is a hallmark of regeneration in Hydra, and this pathway seems to be required in regeneration responses throughout the animal kingdom. The action of Wnt/beta-Catenin signaling is complex, starts minutes after tissue loss, and is poorly understood. There are proposed functions during initial wound healing phase, during the following molecular patterning phase, as well as in the final differentiation of the newly forming structures. We investigate the role of canonical and non-canonical Wnt signaling pathways during Hydra regeneration and re-aggregation at cellular and molecular levels.
Under conditions of regular asexual growth, adult Hydra polyps exhibit astonishing features usually found in animal embryos. All tissues are in a state of continuous replacement and movement. Small new polyps constantly develop by lateral budding. Polyps can also form de novo by re-aggregation of cell suspensions. We are interested to understand the cellular mechanisms involved in creating the 3-dimensional shape of polyp bodies and the underlying molecular patterning systems. Positional information is under control of an oral head organizer and a second signaling center located aborally in the foot. The head organizer is the major inductive signaling center and the equivalent of blastoporal organizers of higher animal gastrula stages, Wnt/beta-Catenin signaling has been demonstrated to represent the key element in the head organizer with axis inducing capacity upon transplantation to ectopic positions. Wnt/beta-Catenin signaling also activates non-canonical Wnt signaling at specific positions in the head and the lower body column, which then causes evagination of tentacles and buds, respectively. In addition, Wnt-interacting, secreted proteins of the sFRP family are activated in the aboral signaling center. Currently, we try to understand in more detail the interactions between oral and aboral signaling and their combined action in setting up axial positional values in newly forming buds, aggregates and regenerating polyps.
Members of the Hydra work group are:
Bert Hobmayer (head)
Birgit Lengerer (PostDoc)
Marion Lechable (PhD student)
Moses Kitilit Kibet (PhD student)
Matthias Achrainer (master student)
Sabina Schönberger (master student)
Kevin Grüner (master student)
Natalie Kolb (animal culture)
Wir interessieren uns für das Regenerationsvermögen von freilebenden Plattwürmern und studieren Regenerationsprozesse in einem Plattwurm-Modellorganismus namens Macrostomum lignano. M. lignano und andere Plattwürmer, u.a. Polycladen, sind für unsere Arbeit besonders gut geeignet aufgrund ihrer beachtlichen Regenerationsleistung und ihrem wahrscheinlich totipotenten, also allmächtigen, Stammzellsystem.
Das Sichtbarmachen von Stammzellen mit BrdU (Bromodeoxyuridin) in ganzen Tieren von Macrostomum lignano und in histologischen Schnitten gibt Hinweise auf Antworten zu folgenden Fragen:
Welche Eigenschaften hat ein Regenerationsblastem?
Wie reagiert das Stammzellsystem auf die Amputation eines Körperteils?
Wieviele Stammzellen sind für eine erfolgreiche Regeneration nötig?
Wir versuchen zudem, das Verhältnis und die Ähnlichkeiten zwischen Regenerationsprozessen und der embryonalen und postembryonalen Entwicklung zu verstehen.Von großer Tragweite ist die Frage, ob wiederholte Amputation und Regeneration eines einzelnen Plattwurms Alterungsprozesse verlangsamen oder sogar umkehren kann.
Mitarbeiter dieser Arbeitsgruppe
- Bernhard Egger (head)
- Isabel Dittmann (PhD student)
- Moses Kibet (PhD student)
- Simon Köll (master student)
- Clemens Gotsis (master student)
- Davina Düngler (master student)