Prof. Dr. Gil Westmeyer
Ingolstädter Landstraße 1, 85764 Neuherberg
Director of the Institute for Synthetic Biomedicine (ISBM)
"In biomedicine, there is a progression from the synthesis of small molecular drugs via the biotechnological production of proteins to the biological engineering of theranostic cells. We seek to promote a careful and safe development in this direction by crafting molecular tools to monitor and control cellular circuits.”
Career
Gil Westmeyer studied medicine and philosophy in Munich and conducted his doctoral work on the molecular basis of Alzheimer’s disease in Christian Haass’ laboratory in Munich before receiving a part of his clinical education at Harvard Medical School.
Starting in 2005, he worked as a postdoctoral Fellow with Alan Jasanoff at M.I.T in the Departments of Biological Engineering and Brain & Cognitive Sciences. In 2011, he joined Helmholtz Munich as a Young Investigators’ group leader and the Technical University of Munich as an assistant professor in 2012.
Since 2021, Gil is the Director of the Institute for Synthetic Biomedicine (ISBM) at Helmholtz Munich. He is also Professor of Neurobiological Engineering at TUM.
ISBM develops and deploys next-generation biotechniques for molecular sensing and actuation of distributed cellular processes to reverse engineer cell-circuit function and guide future cell therapies.
Skills and Expertise
Mammalian cell engineering Synthetic biology
Genetic engineering Molecular imaging
Gil Westmeyer about his work
Professional Career
Director of the Institute for Synthetic Biomedicine (ISBM)
Professor of Neurobiological Engineering – TUM School of Natural Sciences & TUM School of Medicine, TUM
Assistant Professor of Molecular Imaging – Technical University of Munich (TUM)
Young Investigators’ Group Leader Helmholtz Center Munich
Postdoctoral Fellow - Massachusetts Institute of Technology (MIT); Departments of Biological Engineering & Brain and Cognitive Sciences
Honors and Awards
Most important publications
George Al Boustani, Lukas Bichlmaier, Tetsuhiko F Teshima, Oleksandr Berezin, Lennart JK Weiß, Koji Sakai, Kenji Kondo, Lukas Hiendlmeier, Defne Tüzün, Beatrice De Chiara, Marta Nikić, Gil G Westmeyer, Shigeyoshi Inoue, Markus Becherer, Bernhard Wolfrum
Flexible Conductive Paper-Based Sensors for On-Skin Electrophysiological Monitoring and Wearable Applications Flexible, skin-conformable electrodes require materials that combine mechanical robustness, environmental stability, high electrical performance, and biocompatibility. Here, we present a flexible conductive composite film composed of poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS), cellulose nanofibers (CNF), and the ionic liquid 1-ethyl-3-methylimidazolium ethyl sulfate (EMIM ES). The composite is fabricated via a simple aqueous blending and filtration process, yielding a free-standing film with a robust fibrous microstructure. ATR-FTIR analysis confirms the successful integration of all components, while SEM imaging reveals a percolated nanofibrillar architecture that enhances interfacial adhesion and structural integrity. Mechanical testing reveals a tensile strength of up to 335 MPa, accompanied by a strain of 21%, attributed to the increasing CNF content. Composite films with low CNF …Silviu-Vasile Bodea, Rodrigo Gonzalez Laiz, Rhȋannan H Williams, Mariia Gladkova, Dominik Thalmeier, Bastian Rieck, Felix Sigmund, Marie Piraud, Afra Wohlschläger, Dominik Jüstel, Albrecht Stroh, Steffen Schneider, Gil Gregor Westmeyer
Cortex-Wide Preservation of Multi-Stimulus Information across Degrees of Network Synchronization Sensory-evoked cortical responses vary with global network dynamics, yet the link between cortical state and stimulus processing remains unclear. Here, we introduce a paradigm that jointly decodes stimulus identity and network state from wide-field calcium imaging in mice undergoing multisensory and optogenetic stimulation across isoflurane-induced transitions from compartmentalized to synchronized activity. Effective dimensionality, a summary measure of network complexity, correlated well with anesthesia depth, while non-linear contrastive learning achieved >97% stimulus decoding accuracy across all states. Individual cortical regions maintained ≥82.5% accuracy even during deep anesthesia with prominent slow waves. Preservation of stimulus-specific information extended throughout the cortex, demonstrating that distinct representations remain decodable within synchronized networks. Direct optogenetic cortical stimulation exhibited state-invariant decoding performance, contrasting with anesthesia-dependent decline observed for sensory stimuli. Multi-stimulus cortical representations remain decodable across varying levels of network synchronization, with implications for brain-machine interfaces and clinical tools that assess preserved cortical responsiveness under variable arousal conditions.Rafal Hołubowicz, Fangyuan Gao, Samuel W Du, Carolline Rodrigues Menezes, Jianye Zhang, Maria W Hołubowicz, Paul Z Chen, Niklas Armbrust, Julian Geilenkeuser, David R Liu, Dong-Jiunn Jeffery Truong, Gil Gregor Westmeyer, Grazyna Palczewska, Krzysztof Palczewski
Scalable purification enables high-quality virus-like particles for therapeutic translation Emerging molecular therapies introduce enzymatic activity into cells by delivering genes, transcripts, or proteins. Owing to their robust cell-entry capacity, virus-like particles (VLPs) represent a technology of choice in genome editing, where low doses of heterologous proteins and nucleic acids are essential. However, clinical translation of VLP vectors is hindered by inadequate purification methods. Current approaches, relying primarily on ultracentrifugation, suffer from inconsistent product quality and poor scalability. Here, we report the development of a broadly applicable purification strategy that improves the purity and therapeutic efficacy of genome-editing VLPs. Considering the characteristic properties of murine leukemia virus-derived engineered VLPs and HIV-derived engineered nucleocytosolic vehicles for loading of programmable editors, we developed a workflow that involves single-modal and multimodal …Oleksandr Berezin, Alberto Piovesan, Roman Graf, Eleni Samara, Felix Sigmund, Gil Gregor Westmeyer
Multiplexed genetic tags for electron and fluorescence microscopy This protocol provides comprehensive guidance for researchers, including those with limited electron microscopy (EM) experience, on the effective use of genetically encoded, multichannel EMcapsulin reporters in both fluorescence microscopy and EM workflows. EMcapsulins are a set of modular gene reporters that manifest as distinct shapes in EM when expressed in cell culture or model organisms. This protocol encompasses detailed instructions for labeling cells or proteins of interest with fluorescent EMcapsulins, along with biochemical quality control measures. Researchers may also adapt the protocol to develop custom EMcapsulin constructs tailored to their specific experimental requirements.Gil Gregor Westmeyer, Alberto PIOVESAN, Felix SIGMUND, Dong-Jiunn Jeffery Truong, Oleksandr BEREZIN, Niklas ARMBRUST, Mohammad ELGAMACY
Genetically controlled nanoscopy contrast-generating units, genetically controlled structural elements, genetically controlled scaffolds, nanobiomaterial based thereon, and use … The present invention relates to a genetically controlled nanoscopy contrast-generating unit comprising a metal interactor, wherein the metal interactor is compatible with nanoscopy fixation protocols, nanoscopy post-fixation protocols, and nanoscopy metal staining protocols and wherein the metal interactor is a molecule to which metal ions can bind to or react with. The present invention also relates to a genetically controlled structural element, wherein said genetically controlled structural element organizes the genetically controlled nanoscopy contrast-generating unit. The genetically controlled structural element can be an encapsulin and the genetically controlled nanoscopy contrast-generating unit can be one or two murine metallothionein-3, or three chimeric metallothioneins. The present invention also relates to a genetically controlled scaffold, wherein said genetically controlled scaffold spatially organizes the …Inola Kopic, Hu Peng, Sebastian Schmidt, Oleksandr Berezin, Senyao Wang, Gil G Westmeyer, Bernhard Wolfrum
Inkjet-Printed 3D Sensor Arrays with FIB-Induced Electrode Refinement for Low-Noise Amperometric Recordings in hiPSC-Derived Brain Organoids Understanding the functional connectivity and behavior of 3D cell cultures and organoids requires monitoring electrical activity across multiple planes. However, traditional planar microelectrode arrays (MEAs) are limited to surface recordings and struggle to capture signals from deeper layers. Additionally, current fabrication methods face challenges such as prolonged production times and limited design flexibility, which hinder the development of high-precision 3D electrode arrays and affect the quality of cell-electrode coupling. To overcome these obstacles, we introduce a new approach that integrates inkjet printing with focused ion beam (FIB) milling and electrodeposition, resulting in highly customizable 3D MEAs. The FIB milling enables the creation of precise electrode openings at predetermined locations, which is essential for selective recordings within the tissue. The MEAs, fabricated on glass substrates …Ruyu Ma, Luciano M Santino, Tomáš Chobola, Niklas Armbrust, Julian Geilenkeuser, Sapthagiri Sukumaran, Zhizi Jing, Anastasia Levkina, Korneel Ridderbeek, Tingying Peng, Dong-Jiunn Jeffery Truong, Sebastian Doll, Gil Gregor Westmeyer, Jian Cui
A telescopic microscope equipped with a quanta image sensor for live-cell bioluminescence imaging Bioluminescence is an attractive alternative to fluorescence for live-cell imaging; however, its low intensity has prevented widespread adoption. Specialized microscopes compensate by sacrificing spatial resolution, field of view and dynamic range—constraints imposed by the highest-sensitivity camera to date: the electron-multiplying charge-coupled device. Recently, quanta image sensor (QIS) technology has emerged for low-light imaging. Here, we show that a commercial QIS camera has exceptional sensitivity; however, its sensor dimensions necessitate a microscope designed to maximize its properties. We introduce a Keplerian-telescope-inspired microscope setup that, with the QIS, results in modestly improved signal-to-noise ratios at substantially higher spatial resolution, field of view and dynamic range, relative to the state of the art. The telescopic design also confers modularity, enabling multimodal …Julian Geilenkeuser, Niklas Armbrust, Emily Steinmaßl, Samuel W Du, Sebastian Schmidt, Eva Maria Hildegard Binder, Yuchun Li, Niklas Wilhelm Warsing, Stephanie Victoria Wendel, Florian von der Linde, Elisa Marie Schiele, Xiya Niu, Luisa Stroppel, Oleksandr Berezin, Tobias Heinrich Santl, Tanja Orschmann, Keith Nelson, Christoph Gruber, Grazyna Palczewska, Carolline Rodrigues Menezes, Eleonora Risaliti, Zachary J Engfer, Naile Koleci, Andrea Schmidts, Arie Geerlof, Krzysztof Palczewski, Gil Gregor Westmeyer, Dong-Jiunn Jeffery Truong
Engineered nucleocytosolic vehicles for loading of programmable editors Advanced gene editing methods have accelerated biomedical discovery and hold great therapeutic promise, but safe and efficient delivery of gene editors remains challenging. In this study, we present a virus-like particle (VLP) system featuring nucleocytosolic shuttling vehicles that retrieve pre-assembled Cas-effectors via aptamer-tagged guide RNAs. This approach ensures preferential loading of fully assembled editor ribonucleoproteins (RNPs) and enhances the efficacy of prime editing, base editing, trans-activators, and nuclease activity coupled to homology-directed repair in multiple immortalized, primary, stem cell, and stem-cell-derived cell types. We also achieve additional protection of inherently unstable prime editing guide RNAs (pegRNAs) by shielding the 3′-exposed end with Csy4/Cas6f, further enhancing editing performance. Furthermore, we identify a minimal set of packaging and budding modules …Maria V Efremova, Ulf Wiedwald, Felix Sigmund, Silviu‐Vasile Bodea, Hendrik Ohldag, Thomas Feggeler, Ralf Meckenstock, Lorenz N Panzl, Jeroen Francke, Irina Beer, Natalia P Ivleva, Irina B Alieva, Anastasiia S Garanina, Alevtina S Semkina, Franziska Curdt, Nicolas Josten, Sebastian Wintz, Michael Farle, Reinoud Lavrijsen, Maxim A Abakumov, Michael Winklhofer, Gil G Westmeyer
Genetically Controlled Iron Oxide Biomineralization in Encapsulin Nanocompartments for Magnetic Manipulation of a Mammalian Cell Line Magnetic nanoparticles have proven invaluable for biomechanical investigations due to their ability to exert localized forces. However, cellular delivery of exogenous magnetic agents often results in endosomal entrapment, thereby limiting their utility for manipulating subcellular structures. This study characterizes and exploits fully genetically controlled biomineralization of iron‐oxide cores inside encapsulin nanocompartments to enable magnetic‐activated cell sorting (MACS) and magnetic cell manipulation. The fraction of MACS‐retained cells showed substantial overexpression of encapsulins and exhibited both para‐ and ferrimagnetic responses with magnetic moments of 10−15 A m2 per cell, comparable to standard exogenous labels for MACS. Electron microscopy revealed that MACS‐retained cells contained densely packed agglomerates of ≈30 nm iron oxide cores consisting of ultrafine quasicrystalline …Niklas Armbrust, Julian Geilenkeuser, Martin Grosshauser, Luisa Stroppel, Sebastian Schmidt, Tobias Panne, Emily Steinmassl, Florenc Widenmeyer, Niklas Warsing, Oleksandr Berezin, Melike Sabry, Asina Sultanbai, Tobias Santl, Fabian Theis, Julien Gagneur, Dong-Jiunn Jeffery Truong, Gil Gregor Westmeyer
Non-destructive transcriptomics via vesicular export Transcriptomics is a valuable technique for multiplexed monitoring of cellular states. However, its application has been predominantly limited to assays that necessitate cell fixation or lysis, which hinders real-time, longitudinal tracing of RNA expression in live cells. Here, we present non-destructive transcriptomics by vesicular export (NTVE) to enable multi-time-point monitoring of RNA expression dynamics in living inducible reporter cell lines. Stabilized RNA reporter barcodes can be selectively packaged and exported from cells via virus-like particles (VLPs) containing selective affinity handles for convenient multichannel tracking of co-cultured cells. Using an engineered RNA adapter, NTVE exports cellular transcripts from inducible human and murine reporter cell lines with high concordance to conventional lysate-derived RNA-seq. NTVE allows monitoring of transcriptome changes in response to genetic and chemical perturbations in the same cells over time using standard sequencing workflows. NTVE can also be equipped with fusogens to deliver mRNA-encoded effectors or ribonucleoprotein gene editors from sender cells to activate gene reporters in co-cultured recipient cells. In addition, we demonstrate the utility of NTVE in monitoring hiPSC differentiation through daily NTVE analysis tracking multiple lineage-specific marker genes.Inola Kopic, Panagiota Dedousi, Sebastian Schmidt, Hu Peng, Oleksandr Berezin, Annika Weiße, Richard M George, Christian Mayr, Gil G Westmeyer, Bernhard Wolfrum
Inkjet‐printed 3D electrode arrays for recording signals from cortical organoids Monitoring electrical activity across multiple planes in 3D cell cultures and organoids is imperative to comprehensively understand their functional connections and behavior. However, traditional planar microelectrode arrays (MEAs) are intended for surface recordings and are inadequate in addressing this aspect. The limitations, such as longer production times and limited adaptability imposed by standard clean‐room techniques, constrain the design possibilities for 3D electrode arrays and potentially hinder effective cell‐electrode coupling. To tackle this challenge, a novel approach is presented that leverages rapid prototyping processes and additive manufacturing in combination with wet etching and electrodeposition to enhance electrode fabrication and performance. The laser‐patterned MEAs on glass, polyimide (PI) foil, or polyethylene terephthalate (PET) foil substrates incorporate high‐aspect ratio (up to 44 …Wolfgang Wurst, Maren Schuhmacher, Christoph Gruber, Christopher Lang, Ricardo Ruijpers, Lyupka Mazneykova, Ariane Krus, Barbara Tremmel, Friederike Reinhardt, Karoline Kadletz, Zhe Ma, Lucie Casalta, Dina Otify, Brice Beinsteiner, Iolo Balken, Leon Hetzel, Juliane Merl-Pham, Marina Luchner, Lea Krautner, Karin Ganea, Natascha Wiesner, Alexander Emrich, Emirhan Yağmur, Katrin Rager, Gauhar Sagindykova, Niklas Armbrust, Julian Geilenkeuser, Gil Westmeyer, Elvir Becirovic, Martin Biel, Rouzanna Istvanffy, Daniela Vogt-Weisenhorn, Dong-Jiunn Truong, Marion Jasnin, Fabian Theis, Gregor Ebert, Ali Erturk, Andrea Bähr, Nikolai Klymiuk, Florian Giesert
Creating bottom-up RNA transfer vehicles from synthetic protein assemblies Evolution guides biological systems to populate ecological niches, with viruses being one of the most successful examples of that principle. Viruses evolved over billions of years for the efficient transfer of nucleic acids. Although highly diverse, most viruses converged toward a remarkable similarity in the size and shape of their capsids. In contrast, generative models for protein design enable the creation of protein architectures that are absent in nature. Here, we investigate whether AI-designed protein assemblies can be functionalized to construct nucleic acid transport vehicles that are independent of evolutionary trajectories. By combining natural protein domains with synthetic protein assemblies, we create more than a hundred bottom-up RNA transfer vehicles with unique sizes and shapes. These novel vehicles surpass the RNA transfer efficiency of widely used delivery vehicles by several orders of magnitude. Additionally, we demonstrate that their tropism can be programmed by incorporating computationally designed peptide binders and apply them to deliver various therapeutically relevant cargo RNAs, such as Gene Editors, into a wide range of cellular models. We show the in vivo biodistribution of one of these vehicles in a mouse with close to single-cell resolution and use it to perform a gene editing strategy for Duchenne muscular dystrophy in a pig. Our work demonstrates how proteins created by generative AI can be harnessed for the rational engineering of biological systems with desired properties by overcoming the limitations of natural protein diversity.Nathalie Gabriele Schaeffler, Julian Geilenkeuser, Dong-Jiunn Jeffery Truong, Gil Westmeyer, Joachim Raedler
Quantifying Prime Editing Kinetics-Timelapse Fluorescence Data and Model InferenceChristoph Gruber, Lea Krautner, Valter Bergant, Vincent Grass, Zhe Ma, Lara Rheinemann, Ariane Krus, Friederike Reinhardt, Lyupka Mazneykova, Marianne Rocha-Hasler, Dong-Jiunn Jeffery Truong, Gil Gregor Westmeyer, Andreas Pichlmair, Gregor Ebert, Florian Giesert, Wolfgang Wurst
Engineered, nucleocytoplasmic shuttling Cas13d enables highly efficient cytosolic RNA targeting Dear Editor, CRISPR/Cas13 systems are programmable tools for manipulating RNAs and are used in a variety of RNA-targeting applications 1–3. Within the Cas13 family, Cas13d is the most active subtype in mammalian cells 4, 5. Recently, Cas13d was harnessed as an antiviral against diverse human RNA viruses 6, 7. However, Cas13d is barely active in the cytosol of mammalian cells, restricting its activity to the nucleus, which limits applications such as programmable antivirals 4, 5. Most RNA viruses replicate exclusively in the cytosol, suggesting that current Cas13dbased antivirals rely on uncontrolled nuclear leakage and are therefore limited in their efficiency 7. Here, we show that the nuclear localization of Cas13d crRNAs is the fundamental cause of Cas13d’s nuclear preference. To address this limitation, we engineered nucleocytoplasmic shuttling Cas13d (Cas13d-NCS). Cas13d-NCS transfers nuclear …Gil Gregor Westmeyer, Dong-Jiunn Jeffery Truong
A prime editor that makes space for insertions We developed a prime editing (PE) strategy by incorporating a 5′–3′ exonuclease activity, which enhanced the efficacy and precision of ≥30-nucleotide DNA insertions without a secondary nick. Our optimization of the PE complex revealed that recruiting the exonuclease via an RNA aptamer outperformed direct protein fusions.Dong-Jiunn Jeffery Truong, Julian Geilenkeuser, Stephanie Victoria Wendel, Julius Clemens Heinrich Wilming, Niklas Armbrust, Eva Maria Hildegard Binder, Tobias Heinrich Santl, Annika Siebenhaar, Christoph Gruber, Teeradon Phlairaharn, Milica Živanić, Gil Gregor Westmeyer
Exonuclease-enhanced prime editors Prime editing (PE) is a powerful gene-editing technique based on targeted gRNA-templated reverse transcription and integration of the de novo synthesized single-stranded DNA. To circumvent one of the main bottlenecks of the method, the competition of the reverse-transcribed 3′ flap with the original 5′ flap DNA, we generated an enhanced fluorescence-activated cell sorting reporter cell line to develop an exonuclease-enhanced PE strategy (‘Exo-PE’) composed of an improved PE complex and an aptamer-recruited DNA-exonuclease to remove the 5′ original DNA flap. Exo-PE achieved better overall editing efficacy than the reference PE2 strategy for insertions ≥30 base pairs in several endogenous loci and cell lines while maintaining the high editing precision of PE2. By enabling the precise incorporation of larger insertions, Exo-PE complements the growing palette of different PE tools and spurs …Felix Sigmund, Oleksandr Berezin, Sofia Beliakova, Bernhard Magerl, Martin Drawitsch, Alberto Piovesan, Filipa Gonçalves, Silviu-Vasile Bodea, Stefanie Winkler, Zoe Bousraou, Martin Grosshauser, Eleni Samara, Jesús Pujol-Martí, Sebastian Schädler, Chun So, Stephan Irsen, Axel Walch, Florian Kofler, Marie Piraud, Joergen Kornfeld, Kevin Briggman, Gil Gregor Westmeyer
Genetically encoded barcodes for correlative volume electron microscopy While genetically encoded reporters are common for fluorescence microscopy, equivalent multiplexable gene reporters for electron microscopy (EM) are still scarce. Here, by installing a variable number of fixation-stable metal-interacting moieties in the lumen of encapsulin nanocompartments of different sizes, we developed a suite of spherically symmetric and concentric barcodes (EMcapsulins) that are readable by standard EM techniques. Six classes of EMcapsulins could be automatically segmented and differentiated. The coding capacity was further increased by arranging several EMcapsulins into distinct patterns via a set of rigid spacers of variable length. Fluorescent EMcapsulins were expressed to monitor subcellular structures in light and EM. Neuronal expression in Drosophila and mouse brains enabled the automatic identification of genetically defined cells in EM. EMcapsulins are compatible with …Sebastian Schmidt, Constantin Stautner, Duc Tung Vu, Alexander Heinz, Martin Regensburger, Ozge Karayel, Dietrich Trümbach, Anna Artati, Sabine Kaltenhäuser, Mohamed Zakaria Nassef, Sina Hembach, Letyfee Steinert, Beate Winner, Winkler Jürgen, Martin Jastroch, Malte D Luecken, Fabian J Theis, Gil Gregor Westmeyer, Jerzy Adamski, Matthias Mann, Karsten Hiller, Florian Giesert, Daniela M Vogt Weisenhorn, Wolfgang Wurst
A reversible state of hypometabolism in a human cellular model of sporadic Parkinson’s disease Sporadic Parkinson’s Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors. Mitochondrial dysfunction is one contributing factor, but its role at different stages of disease progression is not fully understood. Here, we showed that neural precursor cells and dopaminergic neurons derived from induced pluripotent stem cells (hiPSCs) from sPD patients exhibited a hypometabolism. Further analysis based on transcriptomics, proteomics, and metabolomics identified the citric acid cycle, specifically the α-ketoglutarate dehydrogenase complex (OGDHC), as bottleneck in sPD metabolism. A follow-up study of the patients approximately 10 years after initial biopsy demonstrated a correlation between OGDHC activity in our cellular model and the disease progression. In addition, the alterations in cellular metabolism observed in our cellular model were restored by …Gil Gregor Westmeyer, Dong-Jiunn Jeffery Truong
Intron-encoded extranuclear transcripts for protein translation, rna encoding, and multi-timepoint interrogation of non-coding or protein-coding rna regulation The present invention relates to a method for detecting a nucleic acid construct or part thereof and/or for detecting the expression product of the nucleic acid construct or part thereof, wherein the method comprises inserting a nucleic acid construct or part thereof into an intron or a synthetic intron, wherein the nucleic acid construct comprises certain defined structures according to the present invention. The present invention also relates to the various uses of the method described herein, to the nucleic acid construct, a vector comprising said nucleic acid construct, a cell comprising said nucleic acid construct and/or said vector, and a respective kit.Paul Vetschera, Benno Koberstein‐Schwarz, Tobias Schmitt‐Manderbach, Christian Dietrich, Wibke Hellmich, Andrei Chekkoury, Panagiotis Symvoulidis, Josefine Reber, Gil Westmeyer, Hernán López‐Schier, Murad Omar, Vasilis Ntziachristos
Beyond early development: observing zebrafish over 6 weeks with hybrid optical and optoacoustic imaging Zebrafish are common model organisms in developmental biology, but have recently emerged as imaging targets of research in cancer, tissue regeneration, metabolic disorders, functional genomics, and phenotype‐based drug discovery. Conventionally, zebrafish are studied during the first few days of development using optical microscopy methods. However, optical methods are not suited for imaging at later stages, since the fish become opaque. To address needs to visualize beyond the first days of development, a novel multimodality system for observing zebrafish from larval stage to adulthood is developed. Using a hybrid platform for concurrent selective plane illumination microscopy (SPIM) and optoacoustic mesoscopy, fish (ex vivo) at stages of development up to 47 days at a similar object size‐to‐resolution ratio are imaged. Using multiple wavelength illumination over the visible and short‐wavelength …