Seminare und andere Veranstaltung am Max-Planck-Institut für Stoffwechselforschung oder an kooperierenden Instituten

Gastgeber: Dr. Thomas Wunderlich

Talk by Dr. Sybille Krauß, DZNE Bonn

Abberrant RNA-protein interactions in late-onset diseases
Late onset diseases such as cancer and neurodegenerative diseases represent an enormous burden in our ageing population. An in depth understanding of molecular pathomechanisms is a prerequisite for the development of novel treatment strategies. Our major research interest is in regulatory RNA-protein interactions, an important and often overlooked cellular phenomenon that plays an essential role in disease-development. RNA-function depends on the 3-dimensional structure of the RNA as well as on interaction with RNA-binding proteins. The main goal of our research is to identify and characterize regulatory RNA-protein interactions in healthy and disease tissue, especially in late onset diseases such as cancer and neurodegenerative diseases.In my group, we have identified an RNA-protein complex containing the ubiquitin ligase MID1 that plays an important role in regulating protein synthesis and that is significantly upregulated in late onset diseases including Huntington’s disease, Alzheimer’s disease or certain types of cancer. This aberrant MID1-activity leads to an increased protein production of proteins that are causal for disease-development.Thus, our data suggest that MID1 is a key regulator in disease development. Furthermore, our preliminary results indicate that MID1 localizes to cytosolic RNA granules and interacts with proteins involved in RNA granule assembly, RNA transport and local protein synthesis. In our ongoing experiments we further investigate the exact molecular function of MID1 and its interactome, especially focusing on the molecular pathways that are triggered by MID1 over-expression in disease tissue. Interestingly, these pathways include mTOR-signaling and insulin / insulin-like growth factor-1 (IGF-1) signaling pathways. [mehr]

Talk by Prof. Dr. Dominik Schenten, University of Arizona

Functions of Cytosolic Pattern Recognition Receptors in the Regulation of Adaptive Immunity

Talk by Dr. Martin Pal

Engineering the mouse genome using CRISPR/Cas9 technology

Talk by Dr. Charo Robles

Quantitative proteomics to study circadian control of metabolism

Talk by Prof. Markus Schwaninger, Uni Lübeck

Brain barriers in metabolic regulation

Talk by Dr. Ralf Kühn, Max Delbrück Center, Berlin

Editing of mouse and human genomes using CRISPR/Cas
  • Datum: 11.01.2016
  • Uhrzeit: 14:00 - 15:30
  • Vortragende(r): Dr. Ralf Kühn
  • Dr. Kühn is a tenured scientist at the Max-Delbrück-Center for Molecular Medicine & the Berlin Institute for Health, head of the Transgenic core facility and a lecturer for genetics at the Technical University of Munich in Germany. He has a long track record in mouse genetic engineering technology, including gene targeting in one-cell embryos using zinc-finger nucleases and TALEN. His current research is focused on utilizing and improving the efficiency of CRISPR/Cas9 based mutagenesis in mouse zygotes and human iPS cells, in particular the interference with non-homologous end joining to promote homology-directed repair.
  • Ort: MPI for Metabolism Resarch
  • Raum: Seminar 1
  • Gastgeber: Dr. Thomas Wunderlich
  • Kontakt: thomas.wunderlich@sf.mpg.de
Engineering of the mouse germline to create targeted mutants is a key technology for biomedical research. We use an expedite approach for the generation of mouse mutants by microinjection of engineered, sequence-specific nucleases into one-cell embryos. Such nucleases create targeted double-strand breaks (DSBs) and stimulate DNA repair by non-homologous end joining (NHEJ) or homology directed repair (HDR). NHEJ religates the open ends, frequently leading to frameshift (knockout) mutations by the loss of nucleotides, whereas HDR enables the insertion of targeted (knockin) mutations from gene targeting vectors or oligonucleotides as repair templates. By this means mutant knockout and knockin founders are identified 7 weeks after embryo injections, enabling the fast establishment of mutant lines. Three nuclease generations, ZFNs, TALENs and the CRISPR/Cas9 system were validated in recent years for direct mutagenesis in embryos. In particular, CRISPR/Cas9 enables the generation of knockout and knockin alleles at frequencies of up to 40% and 10%, respectively, among pups derived from embryo injections. Nevertheless, the dominance of NHEJ versus HDR requires further improvement. To tackle this problem we established `traffic light´ reporter lines indicating DSB repair by NHEJ or HDR through the expression of red or green fluorescent proteins. To enhance HDR, we suppressed NHEJ key molecules by gene silencing, by the inhibitor SCR7 or by the adenoviral proteins E1B55K and E4orf6. In cell lines, SCR7 or the knockdown of KU70 and DNA Ligase IV promotes the efficiency of HDR up to 5-fold. Coexpression of the DNA Ligase IV degrading E1B55K and E4orf6 proteins improves the efficiency of HDR up to 8-fold and essentially abolishes NHEJ repair. We are presently using TLR transgenic mice to enhance HDR repair of CRISPR/Cas-induced DSBs by NHEJ suppression in early embryos and somatic cells to optimize the generation of precisely targeted alleles in vivo. [mehr]

Intestinal regulators of whole body metabolism

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