Seminare und Veranstaltungen

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

Talk by Prof.Kazuhiro Nakamura, Nagoya University, Japan

Central neural network to defend life from environmental stresses
A variety of environmental stressors, such as temperature (hot and cold), infection, natural enemies, and starvation, can threaten life. To survive environmental stresses, mammals exert autonomic and behavioral responses as fundamental functions mediated by the CNS. Remarkable progress has recently been made in understanding the central circuit mechanisms of physiological responses to such stressors. A “trunk” neural pathway from the dorsomedial hypothalamus (DMH) to the rostral medullary raphe region (rMR) regulates sympathetic outflows to effector organs for homeostasis. Thermal and infection stress inputs to the preoptic area of the hypothalamus dynamically alter the DMH→rMR transmission to elicit thermoregulatory, febrile, and cardiovascular responses. Psychological stress signaling from the prefrontal cortex to the DMH drives sympathetic and behavioral responses for stress coping, representing a psychosomatic connection from the corticolimbic emotion circuit to the autonomic and somatic motor systems. Under starvation stress, medullary reticular neurons activated by hunger signaling from the hypothalamus suppress thermogenic drive from the rMR for energy saving and prime mastication to promote food intake. I will present a unified neural network for environmental stress responses, which provides novel insights into the integrative central regulation of organ functions that enables mammals to inhabit diverse environments on earth. [mehr]

Talk by Prof. Michael Pankratz, LIMES Institute, Bonn University

Serotonergic modulation of a feeding circuit along the brain-body axis: Insights from a whole animal EM reconstruction of the enteric nervous system in Drosophila
Serotonin has wide-ranging effects on many physiological activities, from feeding and gut motility to mood and motor learning. However, the identity of central serotonergic neurons and the neuronal circuits within which they are embedded are largely unknown at single cell and synaptic level. We have used a scanning transmission electron microscopy dataset of a whole Drosophila larva to elucidate the central sensory-motor circuit that controls swallowing and its coordination with the enteric nervous system. The circuit is composed of Piezo-expressing mechanosensory neurons arrayed along the esophagus which are able to sense the passage of food. Their afferent signal is conveyed onto a set of central serotonergic neurons that project back out via the larval vagus nerve and facilitates swallowing motor pattern. Serotonin release by these neurons modulates serotonin receptor-expressing motor neurons that innervate the muscles underlying esophageal peristalsis. These motor neurons also share an efferent copy of their motor activity with the Piezo neurons sensing food passage. Our analysis reveals an elemental circuit architecture through which successful completion of a rewarding motor task provides a reinforcing and stabilizing signal to the CNS for facilitation of motor learning. [mehr]

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. Martin Gericke, Leipzig University

The role of adipose tissue macrophages in adipocyte degradation
[mehr]

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

Adventures in NPY
[mehr]

Talk by Dr. Claire Foldi, Monash University Melbourne, Australia

Targeting cognitive inflexibility to treat anorexia nervosa – insights into the effects of psilocybin in animal models
  • Datum: 06.07.2022
  • Uhrzeit: 14:00 c.t. - 15:00
  • Vortragende: Dr. Claire Foldi
  • Dr Claire Foldi is a Senior Research Fellow and Group Leader at the Monash Biomedicine Discovery Institute where she leads a program of research focused on the neurobiological underpinnings of anorexia nervosa. Much of this work has centred on how cognition, behaviour and activity within specific neural circuits are involved in the development of pathological weight loss in the activity-based anorexia (ABA) rat model. The Foldi Group is now investigating how psilocybin acts in the brain to modify cognitive behaviour in order to gain insight into its therapeutic potential for anorexia nervosa with funding from the National Health and Medical Research Council of Australia. Dr Foldi also co-leads the Workforce Development stream of the newly-established National Centre for Eating Disorders Research and Translation, and contributes to research projects within the Monash Centre for Consciousness and Contemplative Studies (M3CS) and the Monash Neuromedicines Discovery Centre (NDC).
  • Ort: MPI for Metabolism Research, Gleueler Strasse 50, 50931 Köln
  • Raum: Seminar room 1
  • Gastgeber: Dr. Weiyi Chen
  • Kontakt: weiyi.chen@sf.mpg.de
Psychedelics, including psilocybin and LSD, are undergoing a “renaissance” as possible treatments for a range of psychiatric and neurological disorders, especially because of their fast onset of therapeutic activity. There has been a rapid push to clinical trials since the 2018 designation of psilocybin as a “breakthrough therapy” by the US FDA, based on its efficacy in treatment-resistant depression, including 4 clinical trials currently underway in patients with anorexia nervosa (AN). While the outcomes of these trials will show efficacy one way or the other, it is imperative to understand the biological mechanisms through which psilocybin may act to produce therapeutic outcomes, in order to best direct treatment to individuals likely to respond. This is especially important given the climate of intense media hype that may bias the outcomes of clinical trials based on an expectation of efficacy. We have tested the effects of a single dose of psilocybin on the development of pathological weight loss in the most well-established animal model of AN, known as activity-based anorexia, and suggest a role for reinforcement learning and behavioural flexibility in the positive effects of psilocybin on energy balance. We are now focused on uncovering the neurobiological substrates that underpin these effects, by examining changes in serotonin receptor expression and the brain-derived neurotropic factor (BDNF) signalling pathway. [mehr]

Talk by Sebastien Bouret, Ph.D., University of Lille, France

The not so sweet effect of maternal diet on hypothalamic development
[mehr]

Talk by Prof. Jackson C. Bittencourt, University of São Paulo, Brazil

The Melanin-Concentrating Hormone and the Maternal Behavior/Lactation Period
The Melanin-concentrating hormone (MCH) is a neuropeptide implicated in a wide range of functions. Its role is best described as an orexigenic peptide since acute MCH applications induce an increase in food intake. MCH-immunoreactive fibers (MCH-ir) are found diffused throughout virtually the entire CNS. In contrast, the production of MCH and messenger RNA (mRNA) from its precursor (ppMCH) is concentrated, in mammals, in neurons of two hypothalamic regions: the lateral hypothalamic area [LHA] and the incerto-hypothalamic area (IHy). Only during lactation, MCH-ir neurons and ppMCH mRNA expression appear in new hypothalamic territories, such as the ventromedial part of the medial preoptic area (vmMPOA). The amount of MCH synthesis in this region increases with the progress of lactation, being maximum in the final phase [around 19th- 21st days] when it disappears. The origin of these cells is still unknown. A possible explanation for this phenomenon is the de novo appearance or neuroplasticity of those cells in the vmMPOA region, which would characterize the necessity of MCH signaling to decline the maternal behavior/lactation period of lactating females. [mehr]

Transatlantic Tandem Talk

Healthy Aging: Brain Control of Longevity and Metabolism
In aging populations, questions around the processes of aging become more and more pressing as aging-associated and neurodegenerative diseases such as Alzheimer’s, Parkinson’s and diabetes mellitus increasingly strain our health systems. Understanding the molecular mechanisms involved in degenerative aging processes can help develop new therapeutic approaches that lead to a healthier way of living for older and ill individuals, and eventually for us all. [mehr]

Talk by Prof. Sarah Garfinkel, University of Sussex, UK

Clinical Neuroscience and the Heart-Brain Axis
Interoception incorporates the afferent signalling, central processing and neural and mental representation of internal bodily signals. Historically, within the fields of physiology, psychology and neuroscience, there has been inconsistency in the way that individual differences in interoception are defined and measured. This talk will detail empirical results which demonstrate dimensions of interoception with and without conscious access, with a particular focus on the heart. In normative samples, these interoceptive dimensions are distinct and dissociable. The integration of afferent signals with brain can augment or attenuate perceptive, cognitive and emotion processing. Selective alterations in interoceptive processing are evident in clinical conditions such as schizophrenia and autism, while specific interoceptive disturbances are associated with transdiagnostic symptom expression such as anxiety and dissociation. Understanding the multifaceted nature of interoception and body-brain interactions can open up new avenues for targeted treatment. [mehr]

Talk by Prof. Manuel Mameli, PhD, University of Lausanne, Switzerland

Encoding of aversion in the lateral habenula
Prompt behavioural reactions to external aversive stimuli are essential for individual's survival. He will discuss the contribution of lateral habenula in encoding such aversive stimuli in the brain and the importance of synaptic plasticity in this structure for behaviourally-relevant events. [mehr]

Talk by Dr. Cristina García Cáceres, Helmholtz Zentrum München

Astrocytes emerge as key players in the control of metabolism
The underlying basis for understanding of how brain control energy homeostasis, resides in a functional and coordinate communicating pathways between peripheral endocrine organs and the brain, in which the hypothalamus plays a pivotal role in the integration and processing of peripheral metabolic cues into satiety and feeding signals. Based on human GWAS and targeted mouse mutagenesis models, it has recently been revealed that obesity might due to a brain disease which might be a consequence of a brain misunderstanding the peripheral metabolic status in defense of body weightgain. As matter of fact, a growing body of evidences demonstrate a link between obesity and a defective brain´s nutrient/hormone sensing. Likewise, our studies have shown that hypothalamic astrocytes regulate glucose get access into the brain by sensing peripheral changes in insulin levels and ultimately controlling feeding (García-Cáceres et al., Cell 2016). Using specific transgenic mouse models for targeting metabolic receptors in these glial cells we have demonstrated that not only astrocytes respond to hormones derived from pancreas but also from adipose tissue (leptin), as well as circulating nutrients (lipids, glucose) (Kim et al., Nature Neurosci. 2014; Gao et al., Diabetes 2018; García-Cáceres et al., Cell 2016). Overall our previous work supports that hormone/nutrient signaling in astrocytes is determinant of the manner in which brain sense whole-body metabolic demands. We are now continuing on investigating whether hypothalamic astrocyte-neuron circuits require a precise finely-tuned and coordinated communication with metabolic cues derived from peripheral endocrine organ for maintaining a balanced control of food intake, body weight and metabolism. Furthermore, we hypothesize that impairment of such crosstalk during exposure to hypercaloric environments may contribute to the pathogenesis of obesity and type-2 diabetes. To test this overarching hypothesis, we are developing a functional mouse model for understanding of body-brain connection with particular focus on the role of astrocytes for the control of body weight and energy metabolism in health and disease. [mehr]

Talk by Guadalupe Sabio, PhD, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain

Unravelling the role of p38 and p38 in obesity-related diseases
Protein kinases are the key components of almost every signalling pathway involved in normal development and disease. MAPKs play a key role in the regulation of diverse cellular programs and participate extensively in the control of cell fate decisions such as proliferation, differentiation, and death, as well as in the regulation of stress responses. The main stress-activated MAPKs are the p38 and c-Jun N-terminal kinase (JNK) families. The p38MAPK family has four isoforms encoded by distinct genes located tandemly in 2 chromosomes: p38, , and . Although the role of all p38s have been thought to be similar, we think the less-studied members p38 and  have different and specific regulation and function. We will discuss about our recent findings that suggest that these kinases have specific function and regulation. We will focus our attention in their implication in obesity related diseases. [mehr]

Talk by Dr. Uku Vainik, University of Tartu, Estonia

Uncontrolled eating: a unifying heritable trait linked with obesity,overeating, personality and the brain
Obesity is intertwined with behaviour. Many eating-related behaviours have been proposed to explain obesity, such as food addiction, disinhibition and emotional eating. However, these behaviours tend to similarities based on both statistics and definitions. I propose that these behaviours can be aggregated into a single broad trait – Uncontrolled Eating. Such an approach enables reviewing and meta‐analysing evidence done on each individual behaviour. I review evidence how the aggregated Uncontrolled Eating has robust associations with body mass index, food intake, personality traits, and brain systems. I also map out Uncontrolled Eating’s behavioural similarity with other addictions and psychiatric conditions. In summary, Uncontrolled Eating summarises important behavioural aspects of obesity. [mehr]

Talk by Prof. Susanne la Fleur, University of Amsterdam

Striatal glucose regulates systemic glucose metabolism in humans and rodents
The brain relies on glucose for fuel but has limited storage capacity. To facilitate adequate glucose availability, the brain senses glucose, initiates feeding behaviour, and controls system glucose metabolism. To date, the majority of studies investigating the sensing and central control of glucose have focused on the hypothalamus and the brainstem. However, recent findings have revealed an unexpected and fascinating role for the striatum, a brain nucleus mainly known for its role in reward behaviour, in glucose homeostasis. I will present a series of experiments, in both humans and rodents, supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. With rodent studies we also unraveled the neural route via which the striatum, and especially the nucleus accumbens shell, communicates with the liver to regulate glucose production. [mehr]

Talk by Prof. Anna Beyeler

Link valence and anxiety in the amygdala and insular cortex
[mehr]

Talk by Prof. Tune Hannes Peers, University of Copenhagen

Leveraging human genetics to identify brain cell types modulating susceptibility to obesity.
[mehr]

Talk by Prof. Ana Domingos, University of Oxford

NeuroImmunoMetabolism
[mehr]

Talk by Prof. Christian Ruff, University of Zurich

Dazed and confused? Neural origins of behavioral variability in value-based food choice.
[mehr]

Talk by Prof. Ilona Grunwald Kadodw, TU München

How states and needs shape neural processing and behavior of fruitflies
When interacting with their environment animals constantly make decisions. These decisions frequently aim at maximizing reward while avoiding negative consequences such as energy costs, pain, or long-term disadvantages. Faced with a choice, animals consider and integrate several parameters such as their internal and behavioral state as well as external stimuli. Often decisions are shaped by prior experiences such as exposure to a given stimulus in a certain condition. But preferences and aversions can be innate, and an instinctive reaction can be essential to secure survival. Nevertheless, even these innate preferences need to be evaluated in a context-dependent manner and hence, context strongly impinges on behavior. While it is generally accepted that context influences behavior, our knowledge of the neural mechanisms of how internal state and external conditions alter ongoing behavior is scarce. The goal of my research is to provide a comprehensive understanding of the neural and molecular basis of context-specific behavior. To this end, my group studies how internal states shape chemosensory processing and behavior. In this talk, I will present two examples of our recent work in the fly on reproductive state-dependent decision making and on the role of need and motivation in foraging behavior. [mehr]

Talk by Dr. Cyril Herry, University of Bordeaux

A prefrontal-brainstem pathway mediating active fear behavior
Mammals, including rodents show a broad range of defensive behaviors as a mean of coping with threatful stimuli including freezing and avoidance behaviors. Several studies emphasized the role of the dorsal medial prefrontal cortex (dmPFC) in encoding the acquisition as well as the expression of freezing behavior. However the role of this structure in processing avoidance behavior and the contribution of distinct prefrontal circuits to both freezing and avoidance responses are largely unknown. To further investigate the role of dmPFC circuits in encoding passive and active fear-coping strategies, we developed in the laboratory a novel behavioral paradigm in which a mouse has the possibility to choose either to passively freeze to an aversive stimulus or to actively avoid it as a function of contextual contingencies. Using this behavioral paradigm we investigated whether the same circuits mediate freezing and avoidance behaviors or if distinct neuronal circuits are involved. To address this question, we used a combination of behavioral, neuronal tracing, immunochemistry, single unit and patch clamp recordings and optogenetic approaches. Our results indicate that (i) dmPFC and dorsolateral and lateral periaqueductal grey (dl/lPAG) sub-regions are activated during avoidance behavior, (ii) a subpopulation of dmPFC neurons encode avoidance but not freezing behavior, (iii) this neuronal population project to the dl/lPAG, (iv) the optogenetic activation or inhibition of this pathway promoted and blocked the acquisition of conditioned avoidance and (v) avoidance learning was associated with the development of plasticity at dmPFC to dl/lPAG synapses. Together, these data demonstrate for the first time that activity-dependent plasticity in a subpopulation of dmPFC cells projecting to the dl/lPAG pathway controls avoidance learning. [mehr]

Talk by Dr. Tom Schonberg, Tel Aviv University

New behavioral and imaging findings with the cue-approach paradigm: A non-reinforced mechanism of behavior change
[mehr]

Talk by Prof. Michael Breakspear, QIMR Berghofer Medical Research Institute, Brisbane, Australia

Large-scale brain modes reorganize between infant sleep states and predict developmental outcome in preterms
Sleep architecture carries important information about brain health. Here we show that active compared to quiet sleep in infants heralds a marked change from long- to short-range functional connectivity across broad-frequency neural activity. This change in cortical connectivity is attenuated following preterm birth and pre-empts visual performance at two years. Biophysical modeling shows that active sleep is defined by reduced energy in a large-scale, uniform mode of spatiotemporal neural activity and increased energy in two non-uniform anteroposterior modes. This distinct energy redistribution leads to the emergence of more complex connectivity patterns in active sleep compared to quiet sleep. Preterm-born infants show an attenuation in this sleep-related reorganization of connectivity that carries novel prognostic information. [mehr]

Talk by Dr Michael Krashes, NIDDK/NIH, Bethesda, USA

Defined Paraventricular Hypothalamic Populations Exhibit Differential Responses Contingent on Caloric State
[mehr]

Talk by Prof. Anthony A. Grace, University of Pittsburgh

The Circuitry of Depression: New Findings on Postpartum Depression
[mehr]

Talk by Prof. Ingo Willuhn, Netherlands Institute for Neuroscience

Regionally distinct dopamine fluctuations in the striatum exhibit heterogeneous function in the regulation of motivated behavior
[mehr]

Talk by Prof. Jan Siemens, University of Heidelberg

TRP ion channels – multimodal sensors and Guardians of homeostasis
[mehr]

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 Dr. Ivan de Araujo, Yale School of Medicine

The gut-brain axis and reward
Visceral organs have long been believed to act as major regulators of emotional state. However, the specific role of gut-borne signals in motivated behavior remains elusive to this day. The talk will describe the connectivity and behavioral functions of a neural circuit that links gut sensory neurons to brain reward systems. Implications for our current ideas on the role of the gut-brain axis will be discussed. [mehr]

Talk by Prof. Dr. Harald Möller, MPI for Human Cognitive and Brain Sciences, Leipzig

Insights into Brain Metabolism by quantitative MRI: An Approach from Physics
[mehr]

6th CGA Graduate Symposium

Graduating class of 2014
On December 8, 2017, the 6th CGA Graduate Symposium will take place at the Max Planck Institute for Biology of Ageing. This festive Symposium takes place annually to celebrate the graduating students that have successfully completed their CGA curriculum. Twelve graduate students will present their work in different areas of ageing research. Each session will be accompanied by a key note lecture given by an invited, international renowned expert in ageing research. Our key note speakers will be Hayley Nicholls from Boston, U.S.A., David Tollervey from Edinburgh, UK and Marina Mapelli from Milan, Italy.Sponsored by Eppendorf, New England Biolabs, Eppendorf, Promega and Techniker Krankenkasse [mehr]

Talk by Stephen Smith, Professor of Biomedical Engineering, University of Oxford

Big Data Neuroimaging Studies – HCP and UK Biobank
[mehr]

Talk by Sebastien Bouret, PhD, University of California, LA, USA

Developmental Programming of Hypothalamic Feeding Circuits
[mehr]

Talk by Prof. Sven Enerbäck, University of Gothenburg

Metabolic regulation in adipose tissue, muscle and possibly also in the brain
Brown adipose tissue (BAT) has the unique capacity to regulate energy expenditure by a process called adaptive thermogenesis, which dissipates chemical energy to produce heat. If fully active, the BAT depots of adult humans may burn an amount of energy equivalent to about 4 kg of white adipose tissue (WAT) per year. Needless to say, the identification of BAT in adult humans opens up completely new avenues of therapeutic intervention and offers unique scientific opportunities. This entails a need to better understand the molecular mechanisms that regulate BAT metabolism. This presentation is focused on how BAT, WAT and muscle regulate its uptake and use of substrates for metabolism and how this affects the function of these tissues. These studies have led to identification of transcription factors that regulate cellular glycolysis and substrate preference i.e. glucose or fatty acid uptake and further oxidation. [mehr]

Talk by Kim Ravnskjær, PhD, University of Southern Denmark

Global Analyses of Hepatic Stellate Cell Biology
[mehr]

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

Functions of Cytosolic Pattern Recognition Receptors in the Regulation of Adaptive Immunity
[mehr]

Talk by PD Dr. Michael Potente, MPI for Heart and Lung Research, Bad Nauheim Bad Nauheim

Metabolic regulation of endothelial growth and quiescence
[mehr]

Talk by Prof. Mark Febbraio, Garvan Institute of Medical Research, Sydney

The chameleon role of TLR4 in lipid-induced macrophage inflammation
[mehr]

Talk by Jin Hyung Lee, PhD, Stanford University

Optogenetic fMRI and the Investigation of Global Brain Circuit Mechanisms
Understanding the functional communication across brain has been a long sought-after goal of neuroscientists. However, due to the widespread and highly interconnected nature of brain circuits, the dynamic relationship between neuronal network elements remains elusive. With the development of optogenetic functional magnetic resonance imaging (ofMRI), it is now possible to observe whole-brain level network activity that results from modulating with millisecond-timescale resolution the activity of genetically, spatially, and topologically defined cell populations. ofMRI uniquely enables mapping global patterns of brain activity that result from the selective and precise control of neuronal populations. Advances in the molecular toolbox of optogenetics, as well as improvements in imaging technology, will bring ofMRI closer to its full potential. In particular, the integration of ultra-fast data acquisition, high SNR, and combinatorial optogenetics will enable powerful systems that can modulate and visualize brain activity in real-time. ofMRI is anticipated to play an important role in the dissection and control of network-level brain circuit function and dysfunction. In this talk, the ofMRI technology will be introduced with advanced approaches to bring it to its full potential, ending with examples of dissecting whole brain circuits associated with neurological diseases utilizing ofMRI. [mehr]

Talk by Riekelt Houtkooper, PhD, Academic Medical Center Amsterdam

Pharmacological approaches to restore mitochondrial function
[mehr]

Talk by Amélie Bonnefond, PhD, University of Lille

Post-GWAS functional analyses of variants (and proxy genes) associated with type 2 diabetes
Type 2 diabetes (T2D) is a complex genetic metabolic disorder which has developed into major health problem responsible for early morbidities (e.g. severe vascular complications and cancers) and mortality, with a burden increasing globally. T2D results from the progressive alteration of insulin secretion from pancreatic beta cells on a background of impaired insulin action in sensitive organs and tissues. Whilst the environment is the key risk factor for T2D at the population level, one remarkable feature is the persistence of considerable individual disease risk amongst people sharing same environment. Estimates of T2D heritability range from 40 to 70%. Genome-wide association studies (GWAS) have identified >100 loci independently contributing to T2D risk. Despite this dramatic success, there has been a considerable gap between the knowledge of the genetic contribution of these loci and the understanding of how these loci physiologically impact the disease: indeed, association does not mean causality. Therefore, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to the poor knowledge of how these loci impact T2D pathophysiology. During my talk, I will present several post-GWAS functional studies which enabled the identification of causal genes and pathways involved in T2D pathophysiology. [mehr]

Talk by Professor Roger Cone, University of Michigan, USA

Regulation of Homeostatic Boundary Control and Rheostasis by the Melanocortin-3 Receptor
The MC4R regulates energy homeostasis, and haploinsufficiency produces hyperphagia, hypometabolism, and early onset obesity. In contrast, homozygous deletion of the MC3R does not cause hyperphagia or hypometabolism under normal conditions, producing a mild, late-onset obesity. However, the MC3R plays a critical role in regulating energy homeostasis in response to external and internal nutritional challenges. First, the MC3R regulates energy stores in response to fasting and chronic food restriction. Additionally, there are multiple roles for MC3R in regulation of energy homeostasis in response to reproductive state. MC3R KO mice exhibit defective pregnancy-induced hyperphagia and defective control of energy stores in response to ovariectomy. Thus, MC3R deletion results in defective homeostatic boundary control and rheostasis. Additional data demonstrate a molecular mechanism by which MC3R regulates homeostatic boundary control: MC3R on AgRP neurons acts presynaptically to provide autoregulatory feedback onto MC4R PVN neurons. [mehr]

Talk by Dr. Arthur Liesz, LMU Munich

Immunological Mechanisms in Ischemic Stroke
[mehr]

Selection Workshop for Independent Research Group Leader Position

Selection workshop for Independent Research Group Leader position
14:00 Welcome address14:15 - 14:45 Dr. Henning Fenselau: " Synaptic transmission and plasticity in feeding circuits"14:45 - 15:15 Dr. Christophe Lamy: "Brain glucose sensing and the control of energy homeostasis and behavior" [mehr]

Talk by Professor Paul Fletcher, Cambridge

A cognitive neuroscientific approach to eating and over-eating
[mehr]

Talk by Dr. Martin Pal

Engineering the mouse genome using CRISPR/Cas9 technology
[mehr]

Talk by Dr. Charo Robles

Quantitative proteomics to study circadian control of metabolism
[mehr]

Talk by Jeffrey Friedman, MD, PhD

Leptin and the Neural Circuit Regulating Food Intake and Metabolism
[mehr]

Talk by Dr. Antonia Marin-Burgin

Interaction among excitatory and inhibitory circuits in the hippocampus
The hippocampus is a brain area that is involved in a variety of functions. In particular, the formation of memory and the codification of space depend on the functioning of the hippocampus. Virtually all areas of the hippocampus, and of most parts of the brain, contain excitatory and inhibitory neurons that form individual microcircuits. It is in the interaction between excitatory and inhibitory circuits where appropriate functional responses arise. We study how excitation and inhibition interact to activate neurons in the dentate gyrus of the hippocampus, one of the only regions of the brain in which new neurons are formed throughout life. In this seminar I will present experiments using electrophysiology and calcium imaging aiming to understand the functional role of newborn neurons in the processing of afferent stimuli, with the focus on the synaptic mechanism that generate the unique properties they present. [mehr]

Talk by Dr. Lucas Pontel

Endogenous formaldehyde: a stem cell genotoxin and metabolic carcinogen in mammals
Formaldehyde is a highly reactive chemical used as a preservative and also in many industrial processes. In our cells, this aldehyde is generated as a by-product of several essential biochemical pathways. This ‘endogenous’ formaldehyde is very reactive and can damage proteins and DNA resulting in lethal toxicity. Therefore, cells harbour two protective barriers: the formaldehyde-detoxifying enzyme alcohol dehydrogenase 5 (Adh5) and the Fanconi Anemia DNA repair pathway. The simultaneous inactivation of these two systems leads to haematopoietic stem cell attrition, kidney and liver dysfunction, and development of cancer in mice. My work aims to understand the molecular mechanisms that counteract unwanted consequences of essential metabolism. [mehr]

Talk by Prof. Kohjiro Ueki

Role of Activin B as a novel hepatokine in the regulation of glucose homeostasis
[mehr]

Talk by Prof. Alexander Tarakhovsky, Rockefeller University, New York

Histone Mimicry by Viruses
[mehr]

Talk by Zachary Knight, PhD, University of California San Francisco

The Neurobiology of Homeostasis
[mehr]

Talk by Sebastien Bouret, PhD, Children's Hospital, LA

Developmental Programming of Hypothalamic Feeding Circuits
[mehr]

Talk by Prof. Mirko Trajkovski

Gut microbiota and energy homeostasis
The main interests of our work are the mechanisms underlying metabolic diseases, primarily obesity and insulin resistance. Mammals have two types of fat: brown and white, with opposing functions. Main role of the brown fat is to burn lipids and sugars to produce heat. Brown fat cells also emerge in the subcutaneous adipose tissue (named beige cells) in response to cold, a process known as browning. Promotion of increased brown fat development in humans and experimental mice leads to increased energy expenditure and lean and healthy phenotype without causing dysfunction in other tissues, suggesting the manipulation of the fat stores as an important therapeutic objective. The gut microbiota co-develops with the host and its composition is influenced by several physiological changes, which affect the whole-body metabolism and energy balance. With our integrative research program we are aiming to understand the mechanisms of white adipose tissue browning and the intestinal plasticity in regulating metabolic homeostasis and development of metabolic diseases from the gut microbiota related perspective. [mehr]

Talk by Henning Fenselau, PhD

Melanocortin-driven plasticity of hypothalamic feeding circuits
[mehr]

Talk by Prof. Markus Schwaninger, Uni Lübeck

Brain barriers in metabolic regulation
[mehr]

5th Graduate Symposium Cologne Graduate School of Ageing Research

5th Graduate Symposium Cologne Graduate School of Ageing Research
  • Datum: 10.11.2016
  • Vortragende(r): Diverse
  • Additionally, there will be talks from international guest speakers: Malene Hansen on "Cellular recycling: Role of autophagy in aging and disease", David Rubinsztein on "Autophagy and other pathways that protect against neurodegeneration", Massimo Zeviani on "New genes and mechanisms in mitochondrial biogenesis and disease"
  • Ort: MPI for Biology of Ageing
  • Raum: Lecture Hall
  • Gastgeber: Cologne Graduate School
  • Kontakt: dmorick@age.mpg.de
[mehr]

Talk by Prof. So Young Park

Food & Decision Making in humans: what is the link?
[mehr]

Talk by Dr. Andrew Hoy, University of Sydney

Breast Cancer Swimming in a Sea of Lipid: On a voyage to discover the link between obesity and breast cancer
[mehr]

Talk by Henry Evrard, PhD

Insular cortex: a neuroanatomical insight into interoception, emotion, and self-awareness
[mehr]

Talk by Dr. Alexander Bartelt

Mechanisms guarding brown fat against metabolic stress in cold and obesity
Brown adipose tissue (BAT) needs to dissipate vast amounts ofintracellular and circulating nutrients to sustain its exceptional oxidativemetabolic activity for thermogenesis, and in doing so BAT activity exertsbeneficial metabolic effects on obesity, insulin resistance andatherosclerosis. Identifying factors that protect adipocytes from metabolicstress during the adaptation to cold and obesity may hold great potentialtowards therapeutic approaches for metabolic diseases. As the dramaticmetabolic changes in BAT not only involve dissipation of energy-rich nutrientsbut also the de novo synthesis of new proteins, lipids and cellular organelles,adaptation to cold or excess nutrients might require special mechanisms forincreased quality control of these metabolic processes. While the endoplasmic reticulum (ER) is a critical organelle formetabolic homeostasis, the mechanisms that mediate adaptation of the ER inadipocytes are unclear. We will discuss novel insight into the molecularmechanisms guarding brown fat againstmetabolic stress in cold and obesity. In particular, we will focus on theunfolded protein response and ER-associated protein degradation as the mostcritical pathways by which the ER responds to increased metabolic demand anddiscuss how these are engaged in brown adipocytes. In this context, we haveidentified Nfe2l1, also known as Nrf1, as a novel regulator of ER homeostasisin BAT. Using in vitro systems and mouse models we will address thephysiological, pathological and translational relevance of Nfe2l1/Nrf1 for the adaptationof BAT to cold and obesity. [mehr]

Talk by Denis Burdakov, PhD

Deciphering dynamics and connectivity of brain orexin cells
[mehr]

Talk by Anthony Don, University of New South Wales, Sydney

Developing ceramide synthase inhibitors for insulin resistance and neurodegenerative disease
[mehr]

Talk by Anne Schaefer, MD, PhD

Epigenetic control of neurodegeneration
[mehr]

Talk by Matthew Rodeheffer, PhD, Yale University

Understanding how we get fat: Dietary regulation of adipocyte precursors
[mehr]

Talk by Prof. Ronald Kahn

Insulin action on the brain: Role in metabolism and brain function
[mehr]

Talk by Tatiana Korotkova, PhD, Leibniz Institut für Molekulare Pharmakologie

" To eat? To sleep? To run? Coordination of innate behaviors by lateral hypothalamus"
[mehr]

Talk by Prof. Dr. Christian Wolfrum, ETH Zürich

Mechanisms of brown and white fat formation
[mehr]

Talk by Vincent Prevot, University of Lille, France

Tanycytes: the Hypothalamic Hyperdrive for Metabolic Hormones
The survival of an organism relies on its ability to promptly, effectively and reproducibly communicate with brain networks that control food intake and energy homeostasis. To achieve this, circulating factors of hunger and satiety reflecting nutrient availability must cross the blood-brain barrier (BBB) to reach effectors neurons. A defect in this process invariably leads to uncontrolled body weight. Here I will discuss the key role played in this process by a peculiar type of glial cells named tanycytes, which have their cell bodies lining the floor of the third ventricle and their endfeet contacting the pial surface of the brain. Recent studies indeed suggest that tanycytes, besides regulating hypothalamic BBB plasticity according to nutrient status, capture metabolic signals such as leptin from the bloodstream and transport them towards their cell body for release into the cerebrospinal fluid. Blockade of this conduit for peripheral metabolic factors into the brain of obese individuals is thought to contribute to the pathophysiology of central hormonal resistance. [mehr]

Talk by Scott Sternson, PhD, Janelia Research Campus

The molecular and systems neuroscience of hunger
[mehr]

Talk by Stefanie Brassen, University Medical Center Hamburg-Eppendorf

Reward and cognitive control in aging
[mehr]

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
[mehr]

Imaging human brain insulin sensitivity over the lifespan

[mehr]

Brain Endophenotypes of Obesity

[mehr]

Intestinal regulators of whole body metabolism

[mehr]

NonCode 2015 - CECAD Mini-Symposium on regulatory RNAs

NonCode 2015 - CECAD Mini-Symposium on regulatory RNAs
With the advent of modern sequencing techniques, regulatory RNA biology is gaining significant focus in myriads of avenues ranging from control of development to ageing and ageing-associated diseases. We bring together a group of young, internationally acclaimed scientists specializing in diverse aspects of RNA biology ranging from novel mechanisms of alternative splicing to single cell RNA sequencing. This will be a great opportunity to familiarize with the latest developments in regulatory RNA biology. In order to facilitate easy and convenient scientific exchange, this symposium is free and registration is not required. [mehr]
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