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Prof. Dr. med. Ruxandra Bachmann-Gagescu Associate Professor for Developmental Genetics Department of Molecular Life Sciences and Institute of Medical Genetics, University of Zurich Research Focus: Our research focuses on a group of human Mendelian disorders called ciliopathies, which are unified by shared genetic causes resulting in primary cilium dysfunction. Primary cilia are small non-motile organelles present on the surface of most vertebrate cells where they are involved in transduction of sensory, mechanical or chemical signals and in regulation of signaling pathways during development and cell homeostasis. Typical clinical presentations of ciliopathies include neurological involvement, retinal degeneration and renal fibrocystic disease, as illustrated by Joubert syndrome (JS), an iconic ciliopathy, which is the main focus of our research. To understand the consequences of mutations in JS-associated genes at the molecular level, we are developing iPSC-based neuronal 2D and 3D models using CRISPR/Cas9 genome editing, imaging and –omics approaches such as RNAsequencing and proteomics. In parallel, we are differentiating the iPSC lines harboring mutations in the genes of interest into further cell types affected in ciliopathies using renal organoids. Methods: CRISPR/Cas9 genome editing, next generation sequencing for clone selection and quality control, 2D cortical neuronal differentiation, 3D cerebral organoids, renal organoids Keywords: ciliopathies, primary cilia, Joubert syndrome, iPSCs, neurons, kidney tubular cells Topics: Neuroscience, Disease Modelling, Kidney Biology Publications: https://pubmed.ncbi.nlm.nih.gov/?term=ruxandra+Bachmann-Gagescu&sort=date&size=100 Website: https://www.medgen.uzh.ch/en/forschung/gagescu.html _____________________________________________________________________top |
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Assistant Professor of Regenerative and Movement Biology Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich Research Focus: The primary long-term goal of the Regenerative and Movement Biology lab is directed towards developing stem cell-based therapeutic approaches to treat degenerative loss of muscle mass. To this end, we employ direct lineage reprogramming approaches to convert somatic cells into regenerative-competent myogenic stem and progenitor cells suitable for potential therapies of muscle diseases in animal models. In addition, our lab works on generating muscle stem cells utilizing “blastocyst complementation”, a technique which purposes to produce organs, tissues or cells in animal chimeras via microinjection of induced pluripotent stem cells (iPSCs) into genetically compromised blastocyst-stage embryos. Using this system, we generate both intraspecies chimeras (i.e. mouse-mouse) and interspecies chimeras (i.e. rat-mouse) to assess the feasibility of iPSCs to contribute to the production of myogenic stem cells that can be harnessed to treat muscular dystrophies in rodent models. Methods: Direct lineage conversion utilizing small molecules and transcription factors, isolation and propagation of skeletal muscle stem cells, CRISPR/Cas9 genome editing of genetic mutations that manifest in muscular dystrophies, muscle stem cell transplantation, generation of mouse and rat iPSCs, generation of intraspecies and interspecies chimeras, next generation sequencing assays of skeletal muscle cells Keywords: Skeletal muscle regeneration, muscle stem cells, direct lineage reprogramming, Duchenne muscular dystrophy, iPSCs, blastocyst complementation Topics: Muscle Biology, Muscle Diseases Lab news: https://rmb.ethz.ch/news-and-events.html Publications: https://rmb.ethz.ch/publications.html Website: https://rmb.ethz.ch/ ______________________________________________________________________top |
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Prof. Dr. Matthias Baumgartner Director Research & Education, University Children's Hospital Zurich Head, Division of Metabolism, University Children's Hospital Zurich matthias.baumgartner@kispi.uzh.ch Research Focus: Our research focuses on inherited disorders of methylmalonic aciduria, a rare but life-threatening vitamin B12-related disease which usually presents in the newborn or childhood period. We are using many different approaches to understand disease pathomechanisms and develop novel therapeutic options. Fundamentally, we explore structural biology, cellular biology and biochemistry in our cellular and animal models of disease. In one approach, the group has established multiple patient and control iPSC lines. We are using these to investigate the importance of proteins involved in methylmalonic aciduria, including MMUT, to cell growth and mitochondrial health and have established a cortical differentiation protocol to model neural development, as neurological dysfunction is an important aspect of disease. We will further expand our repertoire to include CRISPR-Cas9 derived isogenic controls as well as 2D striatal differentiation and 3D organoids, which will be ideal for high-content screening of therapeutic molecules. Methods: fibroblast reprogramming, Sendai virus, clonal selection, 2D cortical neuronal differentiation, CRISPR/Cas9 genome editing Keywords: vitamin B12, methylmalonic aciduria, biochemistry, iPSC, neurons, drug development Topics: metabolism, rare disease Publications: https://scholar.google.ch/citations?user=040JFFoAAAAJ&hl=de Website: www.kispi.uzh.ch/de/zuweiser/fachbereiche/stoffwechselkrankheiten/ _____________________________________________________________________top |
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Prof. Dr. Wolfgang Berger Full Professor of Medical Molecular Genetics Director, Institute of Medical Molecular Genetics, University of Zurich berger@medmolgen.uzh.ch Research Focus: Our research focuses on disease modelling of Mendelian eye disorders by making use of induced pluripotent stem cells and genome editing. Diseases include monogenic retinal dystrophies (IRDs), which are generally progressive and may lead to blindness due to dysfunction and gradual loss of photoreceptors and/or supporting retinal pigment epithelial cells. This disease family is characterized by a significant genetic heterogeneity and clinical variability and involves more than 300 associated genes and mapped loci (https://sph.uth.edu/retnet). The second group of diseases includes optic nerve hypoplasia (ONH), persistent hyperplastic primary vitreous (PHPV) and Norrie Disease (ND), the latter two of which are characterized by a maldevelopment of the neuroretina and retinal vasculature. Our disease modelling is performed using 3D retinal organoids, which are chemically differentiated from human induced pluripotent stem cells (iPSCs). In order to study the impact on vascular development, our retinal organoid model is complemented by endothelial cells differentiated from iPSC-derived mesodermal progenitors. Developmental and functional consequences of CRISPR/Cas9-mediated gene knockout or patient variant introduction in the organoid model is studied by morphologic and histologic techniques as well as gene expression approaches (mRNA sequencing (mRNA-seq) and single-cell RNA sequencing (scRNA-seq), where the latter technique provides the benefit of investigating individual subtypes of retinal cells). Other cell-based assays, including minigene assays for characterization of splicing and Luciferase reporter assays for detection of transcriptional activation, allow us to study novel genotype-phenotype associations and possibly lead to the identification of new therapeutic targets. Methods: CRISPR/Cas9 genome editing, next generation sequencing, iPSC-derived 3D retinal organoids, iPSC-derived mesodermal progenitors and endothelial cells, mRNA-seq, scRNA-seq, minigene assay, luciferase reporter assay Keywords: ATOH7, ABCA4, NDP, monogenic/Mendelian retinal diseases, vitreoretinopathies Topics: Retinal development and disease modelling Publications: https://www.medmolgen.uzh.ch/de/publications.html Website: https://www.medmolgen.uzh.ch/de.html ________________________________________________________________________top |
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Head Center for Surgical Research and Research Laboratory Department of Trauma University Hospital Zurich and University of Zurich Research Focus: The main research focus of our research group is the establishment, characterization and analysis of pluripotent stem cells (ESCs, iPSCs) and in particular the study and implementation of their potential for therapeutic and medical applications. One of the main issues with the use of stem cells for clinical applications is the ability to maintain these cells outside of the body (in vitro) in a self-renewing pluripotent and/or multipotent state and to differentiate them to specific cell types. Our work focuses in understanding the molecular mechanisms involved in the regulation of pluripotency and differentiation in preimplantation embryos, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs). Furthermore, we develop and optimize tissue engineering approaches for bone regeneration with pluripotent (iPSCs) and multipotent stem cells. Methods: Embryonic stem cells, IPSCs, Mesenchymal Stromal cells, single cell analysis, CyTOF, in vivo models. Keywords: pluripotency, regenerative medicine, bone Topics: Pluripotency, bone regeneration Publications: pubmed_Cinelli _________________________________________________________________________top |
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Prof. Dr. med. Soeren Lienkamp Assistant Professor Institute of Anatomy, University of Zurich Research Focus: We are interested in embryonic renal organogenesis and the pathophysiology of various genetic renal disorders, including congenital renal anomalies, ciliopathies and cystic kidney disease. We also aim to understand how transcriptional control mechanisms influence renal tubular cell identity. To model genetic diseases, we use in vivo (Xenopus tropicalis embryos) and vitro (direct reprogramming of fibroblasts to renal-like epithelial cells) approaches in combination with CRISPR/Cas9 genome editing, light-sheet microscopy, and machine learning. We are collaborating with the group of Ruxandra Bachmann-Gagescu to differentiate iPSCs into renal organoids to understand the molecular alterations in ciliopathies and kidney malformations. Methods: direct reprogramming, CRISPR/Cas9 genome editing, Xenopus tropicalis embryology, light sheet microscopy, deep learning-based image analysis, renal organoids Keywords: kidney, ciliopathies, cystic kidney disease, Xenopus, renal tubular cells Topics: Renal organogenesis, Kidney disease modelling Publications: https://pubmed.ncbi.nlm.nih.gov/?term=lienkamp+s&sort=date Website: https://www.anatomy.uzh.ch/en/research/lienkamp.html __________________________________________________________________________top |
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Professor for Experimental Ophthalmology, University of Zurich Head of Lab for Retinal Cell Biology, Dept. Ophthalmology, University Hospital Zürich Research Focus: Our research focuses on blinding diseases of the retina with a special focus on age related macular degeneration (AMD) that affects up to 25% of people above the age of 75. We use various animal models to understand specific aspects of disease etiology and progression, and develop therapeutic strategies that are based on neuroprotection and AAV-mediated gene therapy. Photoreceptor neurons form a functional unit with the underlying cells of the retinal pigment epithelium (RPE) that not only form the outer blood/retina barrier but also are crucial for photoreceptor function and survival through the regulation of metabolic support and oxygen delivery from the choroidal blood vessels to photoreceptors. Part of this regulation is the transport and recycling of lipids that originate from the daily process of photoreceptor renewal. We are using iRPE cells differentiated from iPSCs derived from patients carrying genetic variants that confer either increased or decreased risk to develop AMD. These cells closely resemble the in vivo situation in patients and are ideal to study their function in response to various stimuli and conditions that include exposure to neuronal debris with a high cholesterol load and hypoxia, an important factor for disease development. We also use CRISPR editing to inactivate genes in isogenic cells in order to study specific genetic factors for RPE function. Methods: differentiation of iPSC into iRPE cells, CRISPR/Cas9 genome editing, cholesterol efflux, phagocytosis, transepithelial resistance, single cell sequencing, transcriptomics, proteomics, AAV-based gene therapy. Keywords: RPE, lipids, hypoxia, iPSC, neurons, gene therapy Topics: neurodegeneration, gene therapy Publications: http://home.ggaweb.ch/LabForRetinalCellBiology/page1/page1.html Website: http://home.ggaweb.ch/LabForRetinalCellBiology/index.html _______________________________________________________________________top |
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Head of the Translational Molecular Psychiatry, University Hospital of Psychiatry (PUK), Department of Child and Adolescent Psychiatry and Psychotherapy, University of Zurich Chair of the ECNP Thematic Working Group iPSCs platform for Neuropsychiatry Research Focus: The main research focus of the Translational Molecular Psychiatry Research group, part of the University Hospital of Psychiatry Zurich, is on neurodevelopmental disorders, including attention-deficit hyperactivity disorder (ADHD), Autism spectrum disorders (ASD), psychosis, early onset obsessive-compulsive disorder (OCD) and environmental /stress effects. The lab includes research at the pre-clinical as well as at the basic molecular neuroscience, integrating both research fields in a translational manner. The techniques used include molecular genetics, epigenetic, psychopharmacology, neuronal cellular models and biochemical measures. The goal of the research is to elucidate the etiopathology of the disorders discovering biomarkers for early diagnosis and precision personalised medicine, predicting treatment response and outcomes. Currently, the research group has established patient specific iPSC (induced pluripotent stem cell) neuronal modelling to enable personalized medicine, via studies of the neuronal/molecular alterations in a dish of the disorders using 2D techniques. This will provide a non-invasive approach to investigate etiopathology of neurodevelopmental disorders as well as test drug therapy effects. Methods: Hair follicle Keratinocytes, Prick blood cells culturing, Reprogramming via Sendai, Monolayer Neural Progenitor cells generation, cortical neuronal differentiation Keywords: ADHD, ASD, biochemistry, child and adolescent psychiatry, iPSC, molecular biology, NPC, OCD, psychosis, transcriptomics Topic: Neuroscience, Psychiatry Projects: https://www.kjpd.uzh.ch/de/translationale-molekularpsychiatrie.html Publications: https://www.ncbi.nlm.nih.gov/pubmed/Grünblatt Website: https://www.kjpd.uzh.ch/de/translationale-molekularpsychiatrie.html https://www.ecnp.eu/research-innovation/ECNP-networks/iPSCs-platform ____________________________________________________________________top |
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Prof. Dr. med. Simon P. Hoerstrup Full Professor and Managing Director Institute for Regenerative Medicine (IREM), University of Zurich Research Focus: We are working at the interface of basic science and translational research in the field of Regenerative Medicine. So far, we have established the reprogramming of mouse and human cells into iPSC using diverse reprogramming technologies (Retrovirus, Lentivirus, Sendai Virus, Episomal vectors). These cells have been differentiated into either endothelial cells, smooth muscle cells or beating cardiomyocytes. Human iPSC-derived cells have been used for tissue engineering of vascular grafts. Currently, our team is focused on the generation of human iPSC/iPSC-derived cell without using serum or xenogenic reagents for clinical applications. Using microRNA-responsive synthetic mRNAs (RNA switches) we have started to establish - in collaboration with Center for iPS Cell Research and Application (CiRA), Kyoto University - the purification of hiPSC-derived cells, especially the specific elimination of hiPSC. Methods: Reprogramming of human fibroblasts or peripheral mononuclear blood cells; Differentiation of hiPSC into endothelial cell, smooth muscle cells or cardiomyocytes; Purification of differentiated cells using RNA Switch technology Keywords: Induced pluripotent stem cells (iPSCs), Cardiac diseases, Myocardial Infarction, Topics: Tissue Engineering, Cardiac Regeneration, Clinical Translation Publications: https://pubmed Website: https://www.irem.uzh.ch/en.html _______________________________________________________________________top |
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Prof. Dr. med. Sebastian Jessberger Professor of Neuroscience Brain Research Institute, University of Zurich Research Focus: We use a multipronged, interdisciplinary approach to study the molecular and cellular framework of neural stem cell (NSC) biology in the developing and adult brain. We use state-of-the-art imaging-, genome editing-, and transgenesis-based approaches as well as cellular models of human diseases using pluripotent stem cells with the aim to further our understanding of NSC behavior in health and disease. Methods: Mouse and human embryonic stem cells, genome editing, regionalized forebrain organoids, single cell RNA-sequencing, longitudinal imaging. Keywords: brain development, neurogenesis, asymmetric cell divisions, imaging Topics: Stem cells, neuroscience, brain development, disease modeling Publications: https://pubmed.ncbi.nlm.nih.gov/?term=Jessberger+S&sort=pubdate Website: https://www.hifo.uzh.ch/en/research/jessberger.html ______________________________________________________________________top |
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Professor of Biology, Ernst Hadorn Chair Department of Molecular Life Sciences, University of Zurich Research Focus: We use in vitro grown populations of induced pluripotent stem cells to study cellular decision making by quantifying, at high throughput, large numbers of gene and protein activities simultaneously across thousands of single cells within the spatial context of the complex intracellular and multicellular environment. By covering multiple spatial scales relevant to cellular decision making within one sample, we can, for the first time, pinpoint the scale-crossing interactions that govern the collective behavior of molecules and cells and their responses to perturbations during cell differentiation. These insights will change the science of cells and cellular decision making and provide the missing logic of how individual cells can display activities and behaviors that are accurately tuned to the spatiotemporal context of a developing tissue. Methods: high-throughput automated microscopy, large-scale perturbations, subdiffraction imaging at scale, multiplexed protein state imaging (4i), multiplexed transcriptome imaging, computer vision, machine learning, data-driven modeling. Keywords: Genome-wide screening, image-based transcriptomics, crossing scales, computer vision, machine learing, ex vivo image-based diagnostics. Topics: Systems biology, single-cell biology, quantitative cell biology, phase separation, personalized medicine. Publications: https://pelkmanslab.org/publications/ Website: www.pelkmanslab.org _________________________________________________________________________top |
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Prof. Dr. Magdalini Polymenidou Associate Professor of Biomedicine Department of Quantitative Biomedicine, University of Zurich Research Focus: We study the molecular mechanisms of neurodegenerative diseases, focusing on amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ALS and FTD are characterized by the accumulation of RNA-binding proteins, such as TDP-43 and FUS, as well as non-canonically translated dipeptide repeat proteins (DPRs). The molecular mechanisms that trigger aggregation of ALS/FTD-linked proteins, the basis of disease heterogeneity and the mechanisms of neurotoxicity remain elusive. The aim of our research is to address these important questions using a multidisciplinary approach, working at the molecular, cellular and organismal level. Our vision is to gain deep mechanistic understanding of ALS and FTD to inspire rational design of target-based therapies for these devastating diseases. To explore the disease mechanisms in the context of mature human neurons, we generated highly homogeneous, unmodified, human neural stem cells from iPSCs, along with a robust differentiation method that yields functional, interconnected and long-lived neurons within 3D neural cultures. Inducible expression of ALS/FTD-linked proteins in this system is routinely used to understand their behavior and functional consequences in human neurons, as well as evaluate the therapeutic efficacy of antibodies and other compounds. We are currently expanding our efforts to patient-derived neural systems. Methods: Generation of homogeneous and unmodified human neural stem cells, differentiation to cortical neurons and pure astrocytes, 3D neural cultures, lentiviral generation for inducible expression in neurons, single cell RNA-seq, superresolution microscopy, protein aggregation assays. Keywords: ALS, FTD, TDP-43, FUS, DPRs, LLPS, RNA misregulation, protein aggregation, prion-like Topics: Neuroscience, Neurodegeneration, Brain Diseases, Disease Modelling, RNA biology Publications: https://pubmed.ncbi.nlm.nih.gov/?term=polymenidou%5BAuthor%5D&sort=date Website: https://www.polymenidoulab.com ________________________________________________________________________ |
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Prof. Dr. med. Janine Reichenbach Professor for Somatic Gene Therapy Vice-Director, Institute for Regenerative Medicine Research Focus: Development of viral vector- and gene editing-based strategies targeting different monogenic disorders. In general, low availability of the primary patient material is a critical constraint for the early-stage development of gene therapy approaches in rare diseases. Currently, our portfolio of targeted disorders includes rare primary immune-deficiencies and neurodegenerative diseases. Disease modelling with induced pluripotent stem cells (iPSCs) represents a physiologically relevant alternative to primary patient material, with a virtually unlimited source. According to the genetic background of the diseases and the targeted tissue, we employ gene therapy approaches based on either viral vectors (lentiviral vectors and AVV) or gene editing (CRISPR/Cas). Thanks to the ability to differentiate toward specific lineages, patient-derived iPSC allow for the initial testing of the outcomes of the gene therapy approaches by assessment of phenotypic rescue of the functionally impaired target cells. iPSC in vitro models provide an important platform for our initial screenings before proceeding with in vivo studies in animal models for subsequent studies of efficacy and safety in a complex organism. Additionally, iPSC culture makes an attractive source of disease-relevant genotype and phenotype for complex studies on interaction between different cell types, which may prove useful for treating genetic disorders in the future. Methods: Differentiation of iPSC to hematopoietic stem cells, macrophages, neuronal cells, CRISPR editing, lentivirus and AAV based gene therapy. Keywords: CRISPR/Cas genome editing, viral gene therapy, lentivirus, AAV Topics: Gene Therapy, Disease Modelling, Rare Diseases, Immunology, Neurodegeneration. Publications: https://pubmed.ncbi.nlm.nih.gov/ Website: https://www.irem.uzh.ch/en.html ___________________________________________________________________________ |
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Principal investigator Inner Ear Stem Cell Lab Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich Research Focus: Hearing is pivotal for human verbal communication, social interactions and general alertness to our surroundings. Hearing impairment as a consequence has a profound effect on the quality of life of the affected individuals. Specialized sensory cells located into the inner ear translate with remarkable speed and accuracy sound-induced vibrations of different loudness and pitch into chemical signals that can be interpreted by the brain as sound. Loss or damage of these sensory cells results in permanent hearing loss as the human inner ear cannot repair after damage. The long-term goal of our research is to develop novel therapeutic strategies to counteract sensorineural hearing loss by uncovering fundamental biological principles that underlay development and disease. We are making use of in vitro models known as “inner ear organoids” to gain insight into inner ear sensory organ development and to model disease. Further we exploit them as in vitro tools to validate novel therapeutics. Recent developments in the field of stem cell biology allow to generate in vitro inner ear sensory cell types through directed differentiation of pluripotent stem cells (PSCs). The scope of this project is to develop optimized models of human PSC-derived sensory epithelial patches and otic neurons, by leveraging recent advances in bioengineering, organoid culture and organ-on-chip technology. We aim to develop reproducible and robust in vitro models to study inner ear development, model disease and analyze drug-induced ototoxicity and otoregeneration. Methods: PSC derived inner ear organoid, cochlear progenitor culture, in vitro screening Keywords: Inner ear development, Hearing loss, Neuroscience, Disease Modeling Publications: https://www.scopus.com/authid/detail.uri?authorId=24345169900 Website: http://www.orl.usz.ch/forschung/seiten/neurootologie.aspx ________________________________________________________________________top |
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Professor of Systems Neuroscience Institute for Neuroscience, ETH Zurich Research Focus: Despite extensive research, there is up to date no final explanation for the unique cognitive abilities of the human species. Whereas most of the genetic, molecular and cellular components in mammalian brains are quite similar, human neurons seem to display an increased potential for synaptic plasticity. This might be due to a generally higher number of synapses or a prolonged maturation of these in comparison to other mammals and even primates. Non-coding RNAs and especially miRNAs play a significant role in synaptic development and plasticity. Furthermore, particularly the regulatory part of the genome distinguishes humans most from their closest relatives. Nevertheless, the contribution of non-coding RNA dependent mechanisms to human synapse development and plasticity is poorly understood. To study the role of non-coding RNAs in human synapse development, we established a defined human neuronal differentiation protocol without the need for the addition of animal glia cells on two different human induced pluripotent stem cell (iPSC) lines. We show that these neurons are electrophysiological active and investigate synapse formation in detail by analyzing confocal images of pre- and postsynaptic markers at distinct developmental time points. Furthermore, the glia-free differentiation protocol allows us to perform small-RNA sequencing in combination with proteomics and long-RNA sequencing at these same stages. These characterizations are essential for a more detailed functional analysis in the future. By manipulating the expression of specific candidate RNAs, we plan to investigate their role in synaptic maturation as well as effects on neuronal morphology and electrophysiological properties. Newly identified pathways can further be studied in the context of neuropsychiatric diseases using patient-derived iPSC lines. Methods: induced-pluripotent stem cell derived neuron differentiation, imaging, transcriptomics, proteomics, electrophysiology, genome editing Keywords: iPSC, iNeuron, Crispr/Cas9, non-coding RNA, lncRNA, microRNA, synapse, neurodevelopmental disease Topics: Neuroscience, brain development, neuropsychiatric disease Publications: https://pubmed.ncbi.nlm.nih.gov/?term=schratt+g&sort=date Website: http://schrattlab.ethz.ch __________________________________________________________________________top |
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Prof. Dr. Berend Snijder SNF Assistant Professor Institute of Molecular Systems Biology, ETH Zürich snijder@imsb.biol.ethz.ch
Research Focus: The Snijder Lab is interested in deciphering the molecular networks and organizational principles that drive cellular behavior in health and disease. To address these interests, we have pioneered multiplexed image-based drug screening in patient-specific biopsies, a technique we call pharmacoscopy, allowing us to measure patient-centered functional drug responses over hundreds of drugs at the single-cell level. Combined with multi-OMICs integration and deep learning-based image analysis, we aim to identify the molecular and cellular systems underlying human-to-human drug response variability and to improve patient treatment. In this context, we want to elucidate intra- and inter-donor variability in iPSCs derived from peripheral blood mononuclear cells (PBMCs) of a diverse cohort of healthy individuals. To address this, we aim to challenge donor-specific iPSCs in their pluripotent ground state or along differentiation paths, with the goal to reveal cell-intrinsic and cell-extrinsic drivers of phenotypic heterogeneity across individuals and to understand the molecular machineries underlying this variability. In particular, we are interested to unveil the contribution of metabolic states on the trajectory between naïve pluripotency and lineage restriction. Methods: high-content image-based functional screening (pharmacoscopy), PBMC reprogramming, Sendai virus, drug screening, transcriptomics, lipidomics Keywords: pharmacoscopy, high-throughput automated microscopy, multi-OMICs, human-to-human variability, iPSCs, heterogeneity, Topics: Systems biology, personalized medicine, single-cell biology, deep learning, molecular and cellular physiology Publications: https://www.snijderlab.org/#publications Webpage: https://www.snijderlab.org/ ___________________________________________________________________________top |
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Head of Stem Cell Research We use induced pluripotent stem cells (iPSCs) for modelling and understanding human brain diseases and for regenerative therapies with a focus on Alzheimer’s Disease (AD) and ischemic stroke, respectively. The APOE4 allele is the most important genetic risk factor for Alzheimer’s disease (AD), while the presence of APOE3 is risk-neutral and APOE2 is protective. As the main lipid carrier, APOE has a prominent role in the bioenergetic homeostasis of the brain. However, the role of different APOE isoforms for the metabolic state of human brain cells and for functional crosstalk between neurons and astrocytes is still unknown. Using APOE-isogenic iPSCs, we aim to uncover the underlying mechanism of APOE4-mediated metabolic dysfunctions in differentiated human cortical neurons and astrocytes. Thereby we contribute to the mechanistic understanding of AD pathogenesis and get novel insights into the detrimental role of APOE4 and the protective effects of APOE2. Ischemic troke causes a permanent disability to five million people each year. This is largely due to the lack of effective medical treatments that promote long-term recovery. Therefore, we are developing a next-generation regenerative therapy for stroke based on xeno- and integration-free iPSC-derived neural progenitor cells. These are transplanted into a stroke mouse model and tracked longitudinally using in vivo bioluminescence imaging. Our projects specifically focus on improving applicability, safety and efficacy to advance cell therapy for brain injuries towards potential clinical application. Keywords: Alzheimer’s disease, Stroke, induced pluripotent stem cells (iPSCs), neurodegeneration, neurons, astrocytes, neural progenitor cells, disease modelling, cell transplantation, regenerative medicine. Topics: Neuroscience, Neurodegeneration, Neuroregeneration, Brain Diseases Publications: http://www.ncbi.nlm.nih.gov/pubmed/?term=tackenberg+c Website: www.irem.uzh.ch/Tackenberg.html _________________________________________________________________________top |
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Prof. Dr. Ferdinand von Meyenn
Professor of Nutrition and Metabolic Epigenetics
Institute of Food, Nutrition and Health
ETH Zurich
ferdinand.vonmeyenn@hest.ethz.ch Research Focus: Changes in cellular metabolism reflect the balance between intrinsic requirements of a cellular state and adaption to varying extrinsic environments. Metabolic pathways are emerging as a key regulatory mechanism to control cellular function, potential, and state through the dynamic regulation of the epigenome. In particular embryonic development is characterised by significant metabolic, epigenetic and cellular changes associated with different developmental stages, suggesting that metabolism may play a key role in regulating cell fate decisions. But until now, the precise molecular interplay between metabolism and the epigenome remains poorly understood. Our main goal is to understand the mechanisms that link metabolism with epigenetic changes and cellular potential, focusing on pluripotent stem cells and early embryonic development. We are building a comprehensive dataset of metabolic states in human and mouse stem cells and are assessing the impact of induced metabolic changes on PSC potential, histone and DNA methylation, and the relevant epigenetic enzymes. Elucidating these mechanisms will reveal molecular principles involved in the regulation of the epigenome and affecting PSC potential and state. This knowledge will form the basis for novel PSC differentiation strategies for regenerative medicine and will also contribute to our understanding of metabolic disease states and ageing.
Methods: Human and mouse embryonic stem cells; lineage reprogramming; resetting to naive pluripotency; metabolic regulation; epigenetic resetting; next-generation sequencing
Keywords: embryonic stem cells, naive pluripotency, metabolism, epigenetics
Topics: pluripotency, metabolism, epigenetics Publications: https://epigenetics.ethz.ch/publications.html Website: https://epigenetics.ethz.ch ________________________________________________________________________top
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Laboratory of Biosensors and Bioelectronics Institute for Biomedical Engineering ETH Zurich Research Focus: We are promoting a new, bottom-up approach to neuroscience. We create well-defined in vitro neural networks with oriented connections and study their behavior. We use both rat primary hippocampal neurons and human iPSC-derived neurons to build such circuits. We interact with these networks by stimulating selected neurons and record the resulting activities of the networks using optogenetic means and microelectrode arrays (MEAs) including high-density CMOS arrays. We collect TBytes of data that we analyze using machine learning means. We also try to build computational models of the produced living neural networks with the aim to predict the expected behavior of the network. In addition, we also develop stretchable microelectrode arrays to study the strain response of neural networks and the neuro-muscular junction. Methods: Stretchable microelectrode arrays; Optogenetics; Microfabrication; Soft lithography; iPSC-derived neurons Keywords: Neuronal circuits; Induced pluripotent stem cells (iPSCs); Deep learning Topics: Bottom-up Neuroscience; Electrophysiology; Publications: https://lbb.ethz.ch/publications/papers.html Website: https://lbb.ethz.ch/ |
