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WELCOME TO THE MANSUY LAB

Laboratory of Neuroepigenetics
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The Mansuy lab studies the epigenetic basis of complex brain functions and the way life experiences can modify behavior and physiology across generations in mammals. It investigates the mechanisms involving epigenetic factors and chromatin organization that regulate the genome in brain and germ cells, and their causal implication in the expression and transmission of modified traits. The focus is on early life stress and its heritable effects on brain and body health. The potential reversibility of these effects is also examined. Findings in mice are translated to humans by analyses of people exposed to childhood trauma. The long-term objectives of this research are to identify the molecular factors involved in epigenetic inheritance and gain general understanding of this form of heredity to help the development of diagnostic and therapeutic tools for trauma patients in the clinics.

Previous work in the Mansuy lab also examined the epigenetic basis of cognitive functions and discovered the existence of molecules of forgetting. It identified the Ser/Thr protein phosphatases calcineurin and PP1 as suppressors of memory and their role in the epigenetic control of memory formation and synaptic plasticity in the adult brain. It also demonstrated their implication in aging-related cognitive decline, Alzheimer’s disease and neurodegeneration.

The Mansuy lab is part of the Brain Research Institute of the Faculty of Medicine at the University Zurich and the Institute for Neuroscience of the Department of Health Sciences and Technology at ETH Zurich.

EPIGENETIC INHERITANCE

This research focuses on the identification of the ensemble of epigenetic factors in germ cells associated with the inheritance of traits induced by life experiences across generations in mammals. The focus is on experiences involving traumatic stress in early life. Epigenetic factors and mechanisms such as DNA methylation, histone modifications, non-coding RNA and chromatin organization are examined in germ cells but also in brain cells and other cells in the body, and their causal involvement in the expression and the transmission of traits from parent to offspring and subsequent generations is tested. The modes of induction and maintenance of induced epigenetic changes are also studied. The relevance for humans of findings in mice is assessed through collaborative studies in trauma patients with clinicians in Europe and South Asia.

NEUROEPIGENETICS

This research examines the interplay between epigenetic factors and chromatin organization in neuronal cells and the way they interact to regulate genome activity. The purpose is to identify factors that allow the acquisition of information during life experiences and the mechanisms by which they modify the genome to maintain this information across time and determine future neural responses. Chromatin memory in the brain serves several important functions, particularly in cellular identity, neural plasticity, activity-dependent responses and adaptation to the environment. Decoding its molecular basis will have important implications for the understanding of brain functions in health and disease and  for clarifying the aetiology of psychiatric, neurodegenerative and neurological disorders.

RESEARCH TECHNIQUES

The Mansuy lab employs a multidisciplinary approach based on a diverse array of tools and methodologies. It uses environmentally- and genetically manipulated mouse models, organoid and cell culture models together with behavioral testing, metabolic phenotyping, and methods to characterize, and manipulate the genome and epigenome. Classical molecular methods, CRISPR editing and multi-omics approaches including genomics, epigenomics, transcriptomics, proteomics and metabolomics are used, as well as bioinformatics tools and statistical methods.

RNA-binding proteins (RBPs) are the core focus of the research conducted in the Mateescu group. RBPs are crucial to the life cycle of RNA and its role in cell functionality.  The aim is to uncover how these proteins help cells adapt to stress and undergo differentiation.

The group is particularly interested in cell-free RNA (cf-RNA), a novel subject of study in the extracellular landscape. These entities may be a game-changer in disease monitoring and the creation of cutting-edge RNA therapeutics.

The Mateescu group is a place where academic rigour fuels technological breakthroughs, and where research discoveries are translated into revolutionary therapies and diagnostic tools for improving patient health.

Including epigenetics to the principles of heredity changes the fundaments of biology. It can provide an explanation to why and how environmentally induced diseases can affect exposed populations across families. This different way to think about disease etiology opens important perspectives for medicine by pointing to the epigenome as causal vector. It also brings a different view on the rapid adaptation of cells and organisms to our environment, away from the classical genetic logic. This provides a working concept that shifts evolutionary processes in mammals towards chromatin and the epigenome.

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