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

Raum: Seminar 1

Talk by Yoav Livneh, Ph.D., Weizmann Institute, Israel

Brain-body interactions: sensations and predictions in insular cortex
The brain and body are in a continuous dialog that is essential for our physical and mental health. Little is known about how this dialog is achieved at the neurobiological level. A large corpus of work implicates the insular cortex as a central node for bi-directional brain-body communication. However, direct evidence for its functional role is scarce. We developed a microprism-based cellular imaging approach to monitor insular cortex activity in behaving mice across different physiological need states. We combine this imaging approach with manipulations of peripheral physiology and related hypothalamic circuits to investigate the underlying mechanisms. I will first present our recent data suggesting that insular cortex population activity represents both current bodily states, as well as future predicted ones. I will then describe our current efforts to understand these predictions under conditions of conflicting physiological needs, and the potential role of these predictions in regulating bodily physiology. [mehr]

Talk by Prof. William F. Colmers, University of Alberta, Canada

Adventures in NPY

Talk by Scott Sternson, PhD, Janelia Research Campus

The molecular and systems neuroscience of hunger

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 c.t. - 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]

Regulatory RNAs

Regulatory RNAs

Imaging human brain insulin sensitivity over the lifespan

Brain Endophenotypes of Obesity

Intestinal regulators of whole body metabolism

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