Welcome to the homepage of the Institute for Developmental Immunology (IDI) at the Biocenter of the Medical University of Innsbruck. The IDI is currently headed by Prof. Andreas Villunger, PhD, who was appointed as a head of this unit in 2007 as junior professor and is now full professor for Developmental Immunology at MUI.
The Institute is organized in four research groups, run by head Andreas Villunger and associate professors Jan Wiegers, Verena Labi and Sebastian Herzog. Please click the logo to learn more about the respective group!
With their coworkers, DDI investigators explore basic mechanisms of immune cell development and differentiation with a focus on microRNAs and steroid hormones. In addition, we are interested in studying general principles of cellular transformation, focusing on the role of BCL2-regulated cell death and the p53 signalling network as barrier against malignant disease.
All group leaders are involved in training undergraduate as well as graduate students of different life-science disciplines, including biochemistry, biology as well as molecular and human medicine. If you are interested in research training opportunities at different levels (summer students, BSc, MSc, or MD/PhD), or have any teaching related questions, please contact Claudia in administration to organize an appointment with your group leader of interest (Claudia.Ram@i-med.ac.at).
Lab retreat 2020, tyrolean style
MiRNAs are generated from long primary transcripts in which local stem-loop structures are recognized and
cut by the Microprocessor. However, it is still unclear how exactly the enzymatic machinery distinguishes an authentic miRNA hairpin from the thousands of similar folds found in RNA. Here,
Sebastian and his team describe a SAFB2- and ERH-dependent mechanism they refer to as "cluster assistance", in which a suboptimal primary miRNA fold is properly processed only when expressed
together with a standard miRNA on the same transcript. The features that define a primary miRNA are thus not only encoded in the stem-loop itself, but also by the larger sequence
Microtubule targeting agents are used to treat a variety of cancers. These drugs can cause mitotic arrest during which the pro-survival protein MCL1 is targeted for degradation by the pro-apoptotic protein NOXA. This slow degradation of MCL1 is usually assumed to act as a timer defining cell survival. We now identified the E3 Ubiquitin ligase MARCH5 as a factor that controls the stability of the MCL1/NOXA complexes during mitotic arrest with dramatic effects on the survival of the cells during and after mitotic arrest.
The PIDDosome multiprotein complex activates p53 in response to extra centrosomes as seen in polyploid cells. Polyploidization often occurs in cancer but is also part of normal organ development in the liver. This process of failed cytokinesis is induced by E2F transcription factors. Here, we identified the PIDDosome as essential player under transcriptional control by E2Fs to restrict proliferation of proliferation of polyploid hepatocytes during liver development and regeneration. As such, the PIDDosome is a potential therapeutic target to accelerate the regeneration process.
The Labi Lab is hiring
Recently we could secure an FWF stand alone and a TWF grant. If you are excited about the non-coding genome, how small non-coding RNAs (microRNAs) fuel cancer development and how this knowledge can be exploited for disease prevention or treatment JOIN OUR TEAM. We are currently recruiting PhD and MSc students.
In collaboration with Klaus Rajewsky from the MDC Berlin, Verena and her team have identified a mechanism that controls the cellular levels of the BIM protein. The function of BIM in our cells is induction of apoptosis (programmed cell death). Small non-coding RNAs encoded by the miR-17-92 cluster gene can directly bind to the BIM mRNA and dampen the production of the BIM protein. Although both, BIM and the miR-17-92 miRNAs are co-expressed in most cells of our body, this mechanism of cell death inhibition is restricted to specific tissues. In B lymphocytes of the immune system it prevents stress-induced cellular suicide. During embryonic development it promotes normal lung maturation. Hence, this mechanism of apoptosis control is critical for life after birth.
Checkpoint kinase 1 (CHK1) has developed into a promising drug target since tumor cells often depend on CHK1 function for survival. Here, Fabian and his colleagues
describe a previously unrecognized role for CHK1 in establishing and maintaining hematopoiesis.
Ten‐eleven‐translocation (TET) enzymes promote gene expression by catalyzing the oxidation of 5‐methylcytosine in DNA. In this publication that has recently been selected as Editor's Choice we show that TET function is vital for humoral immunity. TET activity guides the transition of germinal center B cells to antibody‐secreting plasma cells, and promotes antibody isotype switching. Loss of TET function favors C‐to‐T and G‐to‐A mutagenesis during somatic hypermutation, a finding of potential significance for the etiology of B‐cell lymphomas and other tumor entities.
How GC B cells exert control over the DNA damage response while introducing mutations in their antibody genes is poorly understood. Here, Verena and here team show that the DNA damage response regulator Checkpoint kinase 1 (CHK1) is essential for GC B cell survival. In particular, they demonstrate that CHK1 inhibition or loss of one Chk1 allele impairs the survival of class-switched cells and curbs the amplitude of antibody production.
Poster Prize for Gerlinde
On the recent 33rd Genes & Cancer Annual Meeting 2019 in Cambridge (UK), Gerlinde went all out and won the Poster Price sponsored by the FEBSJournal. Congratulations! This is pushing her even further to study the BCL-2 protein family in mitotic cell death & the maintenance of genomic stability.