Brain Research Institute
The laboratory is interested in the genetic and epigenetic basis of cognitive functions and behavior in mammals. It aims at better understanding the intracellular signaling pathways and epigenetic mechanisms that underlie higher-order brain functions such as memory formation, behavioral and emotional control in adulthood. It also studies the influence that the environment exerts onto these functions, and on the mechanisms by which environmental, genetic and epigenetic factors interact to modulate behavioral responses across generations. The inheritance of behavioral alterations induced by early trauma and linked to psychiatric diseases such as depression, borderline personality disorder or antisocial behaviors, and their potential treatment are of major interest.
Keywords: epigenetics, cognitive functions, behavior, memory, epigenetic inheritance, synaptic plasticity, protein phosphatases, transgenic mice, proteomics.
4 postdocs, 1 research assistant, 6 PhD students, 2 technicians
Our research on memory focuses on pathways that negatively regulate memory and brain plasticity, and induce forgetting, in particular pathways involving protein phosphatases. Their role and modes of action, and their implication in brain pathologies characterized by cognitive impairment are studied in vivo and in vitro. Mouse models in which the activity of specific protein phosphatases, their substrates or regulatory partners can be modulated inducibly and reversibly in brain areas necessary for memory formation are genetically engineered, and the impact on memory and brain plasticity is examined.
Our work on the inheritance of behavioral alterations induced by early trauma is based on a mouse model of unpredictable maternal deprivation and maternal stress, that exhibits severe behavioral defects comparable to depressive symptoms, cognitive defects, impulsivity and impaired social skills in human and are transmitted across generations. The contribution of epigenetic mechanisms to the behavioral alterations and their transmission, and their potential reversibility or correction by drugs or environmental treatments are under study.
The Mansuy lab has an innovative research program that integrates experimental biology to medical research, and addresses fundamental questions on mental health. It is based on working hypotheses, and uses state-of-the-art methodologies for the design and generation of genetically- and environmentally-engineered mouse models, and their analyses by targeted and high-throughput epigenetic methods, behavioral and electrophysiological techniques, quantitative proteomics, and in vitro and in vivo imaging. It also has a strong link to the clinic, and aims at using comparative methods of analyses in human and animal models. Teaching in neurobiology and epigenetics is provided at a conceptual and practical level.
Molecular, epigenetic and biochemical techniques. Mouse models using conditional transgenesis, knock-out, knock-down, and virus-mediated expression systems. Behavioral testing. Electrophysiological techniques for extracellular and intracellular recordings. Proteomic methods for phosphoproteome and epigenome analyses.
Colloquium on current Brain Research
University of Zurich, ETH Zurich, Swiss National Science Foundation, Roche, NCCR Neural Plasticity and Repair, SystemsX.ch, Österreichische Akademie der Wissenschaften (DOC-fForte), Human Frontier Science Foundation, Slack-Gyr Foundation, Bitterlin Foundation
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