Seminare und Veranstaltungen

Termine am Max-Planck-Institut für Stoffwechselforschung oder an kooperierenden Instituten

Joined Science Day of MPI for Biology of Ageing and MPI for Metabolism Research. [mehr]

Biomedical Seminars Cologne TBA

Talk by Sarah A. Stern, PhD

Coordination of flexible feeding behaviors by molecularly defined insular cortex populations
The insular cortex is a multisensory brain region which is involved in many behaviors, including pain, addiction, social behavior, learning & memory, and feeding/metabolism. To date, the gene expression patterns of the insular cortex have not been systematically studied, but it has generally been assumed to be similar to other cortical areas. However, our data indicates that the insular cortex may have some key transcriptomic differences from other cortical areas, and that these insula-specific genes may have important behavioral functions. To probe this, we conducted single cell sequencing of the insular cortex and compared it to somatosensory cortex. We find that indeed the insular cortex has a distinct transcriptomic makeup compared to somatosensory cortex. We then investigated the function of two insula-specific genes in complex feeding behaviors. Probing the function of these insula-specific cell-types reveals important insights into the functions of the insular cortex vis-a-vis complex motivated behaviors, in particular salience detection and internal state sensing. [mehr]

Talk by Prof. Giles Yeo, University of Cambridge

The use of genetics to identify novel regulators of body shape and size
It is clear that the cause of obesity is a result of eating more than you burn. What is more complex to answer is why some people eat more than others? Differences in our genetic make-up mean some of us are, for a myriad of different reasons, driven to eat more than others. We now know that the genetics of body-weight, on which obesity sits on one end of the spectrum, is in actuality the genetics of how the brain regulates appetite. In this talk, I will discuss the use of different studies, ranging from large population based cohorts, to smaller consanguineous groups of individuals with extreme phenotypes, coupled with ‘omics technologies, to identify novel genes linked to obesity. [mehr]

Cologne Seminars on Ageing "Identifying, Profiling and Therapeutically Clearing Senescent Cells in Alzheimer’s Disease"

Cologne Seminars on Ageing

Talk by Dr. Tim Gruber, Van Andel Institute, Grand Rapids, USA

Food reward thresholds in binge-eating disorder vulnerability are neuro-epigenetically determined by TET-1 dosage.
Midbrain dopamine (mDA) neurons are required for the formation of reward-associated memories, a vital mechanism allowing animals to adapt to their environment. On the flipside, dopaminergic dysfunction caused by repeated exposure to strong reinforcers such as drugs of abuse or hyperpalatable foods can potentially trigger addiction and compulsive, ‘binge’-style eating behaviors, respectively. Intriguingly, humans as well as other animals display striking inter-individual differences in their vulnerability to develop such maladaptive behaviors, which can even be observed despite identical genetics and environment. Thus, we here sought out to explore the role of epigenetic modifications as potential drivers of stochastic variation in the susceptibility to develop binge-eating behavior. To accomplish this, we first performed fluorescence-assisted nuclei sorting (FANS) specifically of mDA neurons from control mice versus mice trained to binge-feed on a hyperpalatable, high-fat diet. When analyzing the DNA methylation landscape of this purified cell type by means of the Infinium Mouse Methylation BeadChip (Mm285), we found that binge-feeding induces a dramatic reorganization of the mDA methylome (2,674 DMR with increased methylation versus 9,799 DMR with decreased methylation; p-value 0.05 and effect size 0.1). The marked loss of methyl marks across multiple genomic regions suggests a prominent role of demethylating enzymes such as Ten-Eleven Translocation 1 (TET-1) dioxygenase, which we interestingly found to be highly enriched in mDA neurons. Consistently, Tet1 haploinsufficient mice (Tet1 +/-) exhibited marked differences in motivated, reward-related behaviors including reduced sucrose preference and attenuated binge-feeding. Notably, bistable segregation into either binge-prone versus binge-resistant animals was significantly amplified in Tet1+/- mice hinting at a potential role in the stochasticity of behavioral variation towards calorie rewards. To reverse already established binge-feeding phenotypes, we started leveraging virus-based approaches to rewire the mDA methylome in a locus-specific, temporally controlled and TET1-mediated fashion in-vivo. In sum, we provide evidence for TET1-mediated DNA demethylation in mDA neurons as an important non-genetic, non-environmental regulator determining flexibility in motivated behaviors and susceptibility to binge-eating disorders. [mehr]
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