Speakers | MxW Summit 2023

Learn more about all confirmed speakers and the title and abstract of their talks!

Confirmed Speakers:

Scientific Talks:

Prof. Dr. Hiroki Ueda
Laboratory for Synthetic Biology, RIKEN, Japan

Title | Towards Systems Biology of Human Sleep/Wake Cycles: Phosphorylation Hypothesis of Sleep

Abstract | The detailed molecular and cellular mechanisms underlying NREM sleep (slow-wave sleep) and REM sleep (paradoxical sleep) in mammals are still elusive. To address these challenges, we first constructed a mathematical model, Averaged Neuron Model (AN Model), which recapitulates the electrophysiological characteristics of the slow-wave sleep. Comprehensive bifurcation analysis predicted that a Ca2+-dependent hyperpolarization pathway may play a role in slow-wave sleep. To experimentally validate this prediction, we generate and analyze 26 KO mice, and found that impaired Ca2+-dependent K+ channels (Kcnn2 and Kcnn3), voltage-gated Ca2+ channels (Cacna1g and Cacna1h), or Ca2+/calmodulin-dependent kinases (Camk2a and Camk2b) decrease sleep duration, while impaired plasma membrane Ca2+ ATPase (Atp2b3) increases sleep duration. Genetical (Nr3a) and pharmacological intervention (PCP, MK-801 for Nr1/Nr2b) and whole-brain imaging validated that impaired NMDA receptors reduce sleep duration and directly increase the excitability of cells. Based on these results, we propose phoshporylation hypothesis of sleep that phosphorylation-dependent regulation of Ca2+-dependent hyperpolarization pathway underlies the regulation of sleep duration in mammals. We also recently developed a simplified mathematical model, Simplified Averaged Neuron Model (SAN Model), which uncover the important role of K+ leak channels in NREM sleep. In this talk, I will also describe how we identify essential genes (Chrm1 and Chrm3) in REM sleep regulation, and propose a plausible molecular definition of a paradoxical state of REM sleep as well as a new project on human sleep/wake cycle measurements for circadian and sleep medicine.

^{1.1.Tatsuki et al. Neuron, 90(1) : 70–85 (2016). 2. Sunagawa et al, Cell Reports, 14(3):662-77 (2016). 3. Susaki et al. Cell, 157(3): 726–39, (2014). 4. Tainaka et al. Cell, 159(6):911-24(2014). 5. Susaki et al. Nature Protocols, 10(11):1709-27(2015). 6. Susaki and Ueda. Cell Chemical Biology, 23(1):137-57 (2016). 7. Tainaka et al. Ann. Rev. of Cell and Devel. Biol. 32: 713-741 (2016). 8. Ode et al. Mol. Cell, 65, 176–190 (2017). 9. Tatsuki et al, Neurosci. Res. 118, 48-55 (2017). 10.Ode et al, Curr. Opin. Neurobiol. 44, 212-221 (2017). 11. Susaki et al, NPJ. Syst. Biol. Appl. 3, 15 (2017). 12. Shinohara et al, Mol. Cell 67, 783-798 (2017). 13. Ukai et al, Nat. Protoc. 12, 2513-2530 (2017). 14. Shi and Ueda.BioEssays 40, 1700105 (2018). 15. Yoshida et al, PNAS 115, E9459-E9468 (2018). 16. Niwa et al, Cell report, 24, 2231-2247. e7 (2018). 17. Ode and Ueda, Front. Psychol. 11, 575328 (2020). 18. Katori et al, PNAS 119, e2116729119 (2022). 19. Ode K.L. et al, iScience 25, 103727 (2022)}

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Prof. Dr. Edward O. Mann
Mann Group, University of Oxford, United Kingdom

Title | Effects of mGluR1 gain-of-function mutation on cerebellar and hippocampal circuits

Abstract | mGluR1 are expressed throughout the brain and are involved regulating neuronal excitability and synaptic plasticity. The Becker laboratory have identified a dominant gain-of-function mutations in GRM1 (encoding mGluR1) causing adult-onset cerebellar ataxia, and have generated a mutant mouse model that recapitulates this phenotype. We have used HD-MEA recordings from acute mouse brain slices to show that the mGluR1 mutation leads to burst firing in cerebellar Purkinje neurons, and are exploring the homeostatic mechanisms that may protect the hippocampus from such pathological hyperexcitability.

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Prof. Dr. Andreas Hierlemann
Bio Engineering Laboratory, ETH Zurich, Switzerland

Title | Development of HD-MEAS and combination with other tools

Abstract | HD-MEAs have proven to be valuable tools for characterizing preparations of electrogenic cells in great detail. It is possible to use subcellular features as well as single-cell and network activity for the phenotyping of dissociated cell cultures or neuronal tissue. The information content of HD-MEA measurements can be enhanced by adding more modalities, such as impedance or electrochemical functional units. In a next step, HD-MEAs can be combined with, for example, high-resolution microscopy and patch clamp techniques to augment experimental possibilities and potential applications.

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Prof. Dr. Michela Chiappalone
DIBRIS, University of Genova / Rehab Technologies Lab, Institute Italiano Di Tecnologia, Italy

Title | Progress in Neuroengineering for brain repair: from in vitro to in vivo studies and beyond

Abstract | In recent years, biomedical devices have been developed to target different neurological disorders. To reach useful therapeutic results, these tools need a multidisciplinary approach and a continuous dialogue between neuroscience and engineering, a field named Neuroengineering. In this talk, M. Chiappalone will highlight the importance of developing novel neuroengineering solutions for brain repair, exploiting both in vitro and in vivo experimental models. She will present her major achievements and introduce the challenges expected for the next years.

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Prof. Dr. Kenta Shimba
Mathematical Biology and Bioengineering Lab, University of Tokyo, Japan

Title | Understanding Cell Diversity in Neuronal Networks with HD-MEA

Abstract | Cortical neurons are typically divided into two broad categories, namely excitatory and inhibitory, which can be further subdivided into several classes. In conventional studies utilizing dissociated cultures, the distinctions among cell types are often overlooked. Nevertheless, different types of neurons are involved in diverse manners in brain functions and diseases of the central nervous system. We aim to understand the relationship between individual cell types and their properties by utilizing a combination of fluorescence imaging and HD-MEA measurements.

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Title | Open Source Hardware & Software Modules for Multimodal Electrophysiology Experiments

Abstract | High-density recordings allow monitoring of neural network activity over space and time but require extensive manual labor during long-term experiments. We propose an automated, remote-controlled experimentation platform that provides consistent media feeding and fuses complementary information acquired through several sensing and stimulation modalities (using MaxWell HD-CMOS MEAs, imaging, and optogenetics). For reproducibility, we use off-the-shelf and open-source 3D printed components as well as our open-source ‘Braingeneers’ Python library.

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Prof. Dr. Yoshiho Ikeuchi
Institute of Industrial Science, The University of Tokyo, Japan

Title | Modeling interregional circuits by connecting neural organoids with a bundle of axons

Abstract | The interregional macroscopic connections serve as a fundamental architecture in the brain. We are currently endeavoring to develop an “organoid-on-a-chip” methodology to model the axonal connections between organoids by utilizing micro-culture devices that guide the growth of axons into a narrow channel, thereby facilitating their self-assembly and synapse formation. Multi-electrode array (MEA) analyses have disclosed that these interorganoid connections promote intricate and vigorous spontaneous network activity within the tissue, which implies that the circuit structures exert a profound influence on their activity. It’s potential applications and perspectives will be discussed.

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Prof. Dr. Nael Nadif Kasri
Nadif-Kasri Lab, Radboud University Medical Centre, Netherlands

Title | Leveraging spontaneous activity in human stem cell derived neurons to model neurodevelopmental disorders

Abstract | Despite considerable progress in elucidating the genetic architecture of NDDs, a major gap exists between the genetic findings and deciphering the pathophysiology of NDDs. Stem cell technology allow us to generate all cell types present in the brain, in vitro, in a patient-specific manner. However, for most NDDs we currently do not know the exact cellular loci of disease. I will explain our strategy to disentangle the cell type-specific contribution to neuronal network phenotypes in the context of NDDs. We generate composite cultures consisting of well-defined cell types differentiated on low and high density micro-electrode arrays (MEA) to probe for neuronal network activity during development. In addition, we combine MEA recordings with transcriptomics within the same experiment (MEA-Seq) to identify molecular pathways that underlie specific neuronal network phenotypes.

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Title | “Go with the flow” – inducing and tracking action potentials with CMOS MEAs

Abstract | The traditional way of studying the brain involves experiments using the nervous system of various organisms. However, at the same time this means studying something highly complex and largely unknown. We build well-defined, small neural networks using PDMS microstructures‎¹ and study them in order to answer fundamental neuroscience questions‎² and to enable personalized medicine‎³.
We interact with these networks using CMOS MEAs which allow the application of an electrical stimulus to selected neurons and axons, and tracking the induced network response with high spatiotemporal resolution.‎<sup>4

1. An experimental paradigm to investigate stimulation dependent activity in topologically constrained neuronal networks; S.J. Ihle, et al.; Biosensors and Bioelectronics, 2021.
2. Engineered biological neural networks on high density CMOS based microelectrode arrays; J. Duru, et al.; Frontiers in Neuroscience, 2022.
3. Topologically controlled circuits of human iPSC-derived neurons for electrophysiological recordings; Girardin, et al.; Lab-on-a-chip, 2022.
4. Investigation of the input-output relationship of engineered neural networks using high-density microelectrode arrays; J. Duru, et al.; Biosensors and Bioelectronics, 2023, submitted.</sup>

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Prof. Dr. Tarja Malm
Malm Lab, University of Eastern Finland, Finland

Title | Modeling brain functions using microglia-containing organoids

Abstract | To study microglia-neuron interactions in the context of developing brain, we have developed a protocol to incorporate erythromyeloid progenitors into cerebral organoids. Our data show that EMPs migrate to cerebral organoids and mature into microglia-like cells and interact with synaptic material and support the emergence of more mature neuronal phenotypes. We have now further optimized the organoid model to enhance the neuronal maturation and carry out in depth electrophysiological characterization over the 8-month culture period. Our data show that we have an electrophysiologically relevant model that recapitulates neuronal maturation in firing activity in a time dependent manner.

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Prof. Dr. Paolo Massobrio
DIBRIS, University of Genova, Italy & National Institute for Nuclear Physics (INFN), Genova, Italy

Title | On the road to achieving brain-on-a-chip using MEA technology: role of connectivity and heterogeneity in the emerging patterns of electrophysiological activity

Abstract | The brain is characterized by the presence of different neuronal populations (e.g., cortical, hippocampal neurons) which interact following well-defined principles of connectivity. In this talk, I will present recent advancements to engineer in vitro networks of interconnected neuronal assemblies to MEAs keeping three fundamental properties of the brain: heterogeneity, three dimensionality, and modularity. This approach paves the way to recreate interconnected brain-regions-on-a-chip providing insights to understand the mechanisms at the basis of the interactions among neuronal populations.

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Dr. Rouhollah Habibey
Busskamp Lab, University of Bonn, Germany

Title | Long-term morphological and functional dynamics of human stem cell-derived neuronal networks

Abstract | Long-term electrophysiological characterizations of developing human iPSC derived neuronal networks requires understanding network-wide morphological changes over time. Parallel microscopy and cMOS-recordings revealed large-scale structural changes from homogeneously distributed neurons to the formation of neuronal clusters. This leads to constant shift in the position of neuronal cells and corresponding changes in spatial distribution of the network activity maps over months.

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Dr. Michele Bertacchi
Studer Lab, Institut de Biologie Valrose (iBV), France

Title | Modelling NR2F1 deficiency in human brain organoids

Abstract | Widely expressed in the developing mammalian brain, the transcriptional regulator NR2F1 plays key roles during retinal and cortical development. However, it is still unknown how its expression level and function are regulated in human cells. We used brain organoids as an in vitro model to challenge the effect of FGF signalling on NR2F1 expression. Here we show that FGF8-mediated regulation of NR2F1 levels affects the regional identity of neural progenitors and neurons in telencephalic brain organoids, ultimately impacting the establishment of cortical circuits.

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Dr. Melanie Einsiedler
Schaeren-Wiemers Lab & Women’s Brain Project, University of Basel, Switzerland

Title | Are there sex differences in in vitro models for brain disorders? – A perspective from the Women’s Brain Project

Abstract | Novel in vitro tools, from inducible pluripotent stem cells to organoids, promise to revolutionize research and drug discovery for brain disorders. Increasing evidence indicates key sex differences in the physiology and pathology of the brain. The Women’s Brain Project is a Swiss based non-profit that studies sex and gender differences in brain and mental disorders as the gateway to precision medicine. Here we will provide an overview of sex differences in currently used in vitro models and discuss their relevance for basic science and drug development.

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Dr. Melisa Ho
GSK, USA

Title | Development of an iPSC derived 2D triculture MEA functional model for drug discovery in Neurodegeneration

Abstract | Neurodegeneration (ND) is a disease characterized by progressive loss of neurons and resulting in cognition/motor deficit. Human genetics indicates various dysregulated pathways involved in the risk of developing ND. We have developed a human iPSC-derived 2D bi/triculture model to examine functional interaction among neural cells. Using amyloid beta as an exemplar, we have studied the structural and functional response of the neurons in the 2D bi/triculture by using imaging and multielectrode array (MEA) assays. Our PoC data affirm the utility of MEA assay for testing biological/therapeutic hypothesis.

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Prof. Dr. Monica Frega
Clinical Neurophysiology department, University of Twente, the Netherlands

Title | A human in vitro model of the ischemic penumbra 

Abstract | In ischemic stroke, treatments to protect neurons from irreversible damage are urgently needed. In this talk, Monica Frega will present recent advancements in stroke research, by using hiPSCs-neuronal networks cultured on MEAs as a tool to investigate the effect of ischemia on neuronal functionality and to test new candidate drugs and treatments.

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Dr. Ouissame Mnie Filali
FUJIFILM Cellular Dynamics Inc. (FCDI), Netherlands

Title | Expanding Application of HD-MEA across 2D and 3D-cultured iPSC-derived iCell® Neuronal Cell Types

Abstract | Recording iPSC-derived neural cell activity using HD-MEA is a powerful tool for disease modeling. In this session, we’ll discuss technical considerations for culturing and recording iCell iPSC-derived neuronal cell types on MaxWell’s HD-MEA platforms. We’ll then demonstrate the use of HD-MEA for characterizing disease models for: 1) Parkinson’s disease using patient-derived iCell DopaNeurons with LRRK2 or GBA mutations; and 2) Frontotemporal Dementia using progranulin knockout iCell Induced Excitatory Neurons. Last, we’ll show preliminary data of neural activity in 3D iCell NeuroSpheres.

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Prof. Dr. James Ellis
Ellis Lab, Hospital for Sick Children, Canada

Title | NDD-Ephys-dB: A human neurodevelopmental disorder electrophysiology database

Abstract | An accessible MEA and patch-clamp database curating results will promote data-sharing of published results and data-mining by computational neuroscientists. We use Rett syndrome data from Mok et al, Translational Psych 2022 in a prototype resource for human iPSC-derived 2D neuronal networks and single neuron electrophysiology. The database contains downloadable raw and curated data, and includes visualization and data filtering using a GUI. Our goal is to expand the NDD-Ephys-dB resource to include 3D and high-density MEA results to advance studies of all neurodevelopmental disorders.

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Dr. Julian Bartram
Bio Engineering Laboratory, ETH Zurich, Switzerland

Title | Probing the synaptic basis of spiking using parallel HD-MEA and patch-clamp recordings

Abstract | Neuronal spiking is largely controlled by the magnitude and temporal relationship of the excitatory (E) and inhibitory (I) inputs. Uncovering the synaptic input patterns that determine postsynaptic spiking could not only provide fundamental insights into the network’s dynamical regime, but may also yield advanced disease biomarkers. We, therefore, developed an approach to reconstruct – in parallel – the E and I input activity of individual neurons during recurrent network activity in vitro. In line with predictions of balanced network theory, we revealed a sophisticated spiking regime governed by fine-tuned E/I ratio fluctuations.

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Science Communication Session:

Dr. Giorgia Guglielmi
PhD-trained science writer and communicator whose stories have appeared in Nature, Science, Scientific American, and more, Switzerland

Title | Maximize research impact: working with traditional and social media

Abstract | Mass media can boost the reach of scientific findings, and social media platforms provide researchers and organizations with the opportunity to engage with the general public. In this seminar, I’ll share tips and knowledge on how to work with press officers, talk to journalists and promote your own work on social media.

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