Biology subjects

Fischer, F.

Publications and source records attributed to Fischer, F..

10 recordsLinked to original sources

bioRxiv2026

A water compartment cell culture lid enables stable longitudinal recording of neuronal networks in vitro

Longitudinal electrophysiological recordings of neuronal networks are essential for studying network maturation, plasticity, and pharmacological responses. Yet current microelectrode array (MEA) approaches are limited by evaporation-induced drift in culture conditions, exacerbated by heat dissipation from active recording electronics on CMOS-based high-density MEAs. We present a cell culture lid featuring a water compartment at its interface that eliminates evaporation whilst maintaining gas exchange. Combined with a custom incubator that uses independent temperature control of the MEA to prevent condensation, the system enables stable, un-interrupted recordings for weeks. We show that perturbations in firing rate and functional connectivity following medium exchange are significantly reduced by suppressing evaporation. We demonstrate continuous 35-day recordings of patterned human iPSC-derived neuronal networks with a single medium exchange, revealing the spontaneous emergence and consolidation of spatiotemporal firing patterns during maturation. All design files are provided to facilitate adoption across culturing platforms, enabling un-interrupted longitudinal interfacing with network dynamics for studies of plasticity, chronic pharmacology, and developmental trajectories in individual cultures.

neuroscience↗

bioRxiv2025

Why they occur here but not there - a case study of Great Spotted Woodpeckers in the city of Munich

O_LIMany animal species can occur in the urban environment. The factors determining whether a particular species can live in a particular place in the city are, however, often not known. Such knowledge is needed to be able to design a built environment that is suitable for species. C_LIO_LIThe Great Spotted Woodpecker, Dendrocopos major, breeds in self-made cavities in trees and regularly occurs in cities. Here, we used a number of approaches to elucidate the factors that influence the occurrence of woodpeckers in the build-up area of the city. C_LIO_LIWe studied the occurrence of D. major on 103 squares in Munich, Germany and linked their presence to a number of square features such as square size, position in the city, tree occurrences, and a number of other variables. We also observed the presence of woodpecker cavities and undertook behavioural observations to study tree use. C_LIO_LIWoodpeckers were observed on 60% of the squares. A random forest model showed that the number of humans on squares negatively affected woodpecker occurrence, while a number of tree-related variables, such as tree density, tree diversity, the number of old trees (>60 cm DBH), and the sum of DBH of trees on the square, positively affected occurrence. Some other variables were also important, such as the amount of green in the surroundings and the distance to the city centre. C_LIO_LINests were found only in trees with a DBH>20 cm, and there was a distinct preference for larger trees, whereby a range of species was accepted. Behavioural observations showed that woodpeckers used a wide variety of trees, including small ones. Particular species and trees with a DBH>20 cm are preferred. C_LIO_LIOur study shows that humans can design public places for the presence of the Great Spotted Woodpecker by providing a locally high abundance of trees of different species with total DBH close to 25m. Trees in the surroundings and the presence of softwood trees with >40 cm will make it more likely that woodpeckers will use such sites in the city. C_LI Statement on inclusionOur study brings both established scientists with permanent faculty positions with Ph.D.-students and students of the 2nd year of their B.Sc.-studies or 1st or 2nd year of their M.Sc.-studies for whom this work is the first experience in the publication of scientific results. Students were particularly encouraged to contribute to question and hypothesis development as well as analysis and interpretation.

ecology↗

bioRxiv2025

Toll receptors mediate tissue intrinsic surveillance against aberrant cells by detecting cell fate aberrations

Tissue-intrinsic surveillance systems play an important role in maintaining tissue health by detecting and eliminating aberrant cells. One such system, interface surveillance, is activated by differences in cell fate programs between neighboring cells. Activation of interface surveillance drives separation and elimination of aberrant cells by recruitment of actin regulators and Myosin II to neighboring cell contacts, as well as activation of JNK signaling and apoptosis in cells at this interface. Here, we uncover the role of long Toll receptors (Toll-2, Toll-6, Toll-7, Toll-8) as key mediators of interface surveillance in Drosophila wing imaginal discs. Using genetic mosaics combined with spatial mapping of Toll receptor expression patterns, we demonstrate that differences in long Toll receptor expression levels between neighboring cells trigger all hallmark responses of interface surveillance. This response is position-dependent and relies on the comparison of expression levels established by cell-fate-specifying programs. Specifically, we show that the expression of long Toll receptors is regulated by multiple fate-patterning pathways, giving rise to a combinatorial cell surface code that is deregulated in developmentally aberrant or oncogenic cells. Remarkably, Toll receptor-mediated surveillance operates independently of canonical NF-{kappa}B signaling, and rather mirrors a distinct role of long Toll receptors in modulating cell-cell affinity via actomyosin dynamics during early embryogenesis. Our findings identify long Toll receptors as integrators of developmental patterning and tissue homeostasis mechanisms and provide insights into how tissues detect and respond to potentially oncogenic mutations that misregulate cell fate specification pathways.

cell biology↗

bioRxiv2024

The global spectrum of tree crown architecture

Trees can differ enormously in their crown architectural traits, such as the scaling relationships that link their height and crown size to their stem diameter. Yet despite the importance of crown architecture in shaping the structure and function of woody ecosystems, we lack a complete picture of what drives this incredible diversity in crown shapes. Using data from >500,000 globally distributed trees, we explored how climate, disturbance, competition, functional traits, and evolutionary history constrain the height, crown size and shape of the worlds tree species. We found that variation in height scaling relationships was primarily controlled by water availability and light competition. Conversely, crown width was predominantly shaped by exposure to wind and fire, while also covarying with other functional traits related to mechanical stability and photosynthesis. Additionally, several plant lineages had crown architectures that defy their environments, such as the exceedingly slender dipterocarps of Southeast Asia, or the extremely wide crowns of legumes in African savannas. Our study charts the global spectrum of tree crown architectural types. It provides a roadmap for integrating crown architecture with vegetation models and remote sensing observations, so that we may better understand the processes that shape the 3D structure of woody ecosystems.

ecology↗

bioRxiv2024

AARS Online: a collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases

The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various non-translational activities, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the twenty-two coded amino acids are handled by sixteen evolutionary Families of Class I aaRS and twenty-one Families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like tool curated by an international consortium of field experts. This platform systematizes existing knowledge about the aaRS by showcasing a taxonomically diverse selection of aaRS sequences and structures. Through its graphical user interface, AARS Online facilitates a seamless exploration between protein sequence and structure, providing a friendly introduction to the material for non-experts and a useful resource for experts. Curated multiple sequence alignments can be extracted for downstream analyses. Accessible at www.aars.online, AARS Online is a free resource to delve into the world of the aaRS.

biochemistry↗

bioRxiv2023

Scaling cross-tissue single-cell annotation models

Identifying cellular identities (both novel and well-studied) is one of the key use cases in single-cell transcriptomics. While supervised machine learning has been leveraged to automate cell annotation predictions for some time, there has been relatively little progress both in scaling neural networks to large data sets and in constructing models that generalize well across diverse tissues and biological contexts up to whole organisms. Here, we propose scTab, an automated, feature-attention-based cell type prediction model specific to tabular data, and train it using a novel data augmentation scheme across a large corpus of single-cell RNA-seq observations (22.2 million human cells in total). In addition, scTab leverages deep ensembles for uncertainty quantification. Moreover, we account for ontological relationships between labels in the model evaluation to accommodate for differences in annotation granularity across datasets. On this large-scale corpus, we show that cross-tissue annotation requires nonlinear models and that the performance of scTab scales in terms of training dataset size as well as model size - demonstrating the advantage of scTab over current state-of-the-art linear models in this context. Additionally, we show that the proposed data augmentation schema improves model generalization. In summary, we introduce a de novo cell type prediction model for single-cell RNA-seq data that can be trained across a large-scale collection of curated datasets from a diverse selection of human tissues and demonstrate the benefits of using deep learning methods in this paradigm. Our codebase, training data, and model checkpoints are publicly available at https://github.com/theislab/scTab to further enable rigorous benchmarks of foundation models for single-cell RNA-seq data.

bioinformatics↗

bioRxiv2023

A cell surface code mediates tissue-intrinsic defense against aberrant cells in epithelia

Tissue-intrinsic error-correction mechanisms allow epithelial cells to detect aberrant neighboring cells and cause their removal from the tissue. The molecular mechanisms which grant cells the ability to compare their internal states is unknown. Here we demonstrate that comparison of cell identity, created by cell-fate-specifying transcription factors and patterning pathways, is conveyed through a specific set of cell surface molecules. We demonstrate that Drosophila imaginal discs express a range of cell surface molecules previously implicated in neuronal axon guidance processes, such as members of the Robo, Teneurin, Ephrin, Toll-like or atypical Cadherin families. Expression of these molecules is regulated by intrinsic fate-patterning pathways of the disc but also by aberrant expression of oncogenic RasV12. Importantly, mosaic clones deregulating individual cell surface molecules are sufficient to induce all hallmarks of interface surveillance, a tissue-intrinsic error-correction mechanism previously shown to be induced by cells with aberrant activation of fate-patterning pathways. Specifically, cells with deregulated expression of Robo2 and Robo3 induce actomyosin enrichment, bilateral JNK signaling and apoptosis at mosaic clone interfaces in imaginal discs. Moreover, deregulation of Robo2 levels, which is normally expressed in a complex endogenous pattern, induces these interface surveillance hallmarks in a Robo2-pattern-specific manner. Taken together, our work indicates that these cell surface molecules mediate cell fate recognition in epithelial tissues and thereby contribute to the maintenance of epithelial health by initiating detection and removal of aberrant cells during development and adult tissue homeostasis.

cell biology↗

bioRxiv2022

3D-Mass Spectrometry Imaging of Micro-scale 3D Cell Culture Models in Cancer Research

Three-dimensional (3D) human cell culture models have emerged as a key technology for personalized medicine and for phenotypic compound screening in more disease-like in-vitro systems. Mass spectrometry imaging (MSI) is one of the most versatile label-free techniques that enables simultaneous generation of spatial maps for multiple relevant molecules in these 3D-models. Here, we present an integrated platform for 3D-MSI of 3D-cell cultures comprising 3D-printed metal casting molds for freezing and embedding, MS imaging of 100 serial cryosections and their computational elastic 3D-reconstruction. With this platform, we monitored multiple lipids that were selectively associated with different cell-types or cell-cell interactions within 300 m-scale fibroblast and colon cancer biculture spheroids. Our findings suggest that 3D-printing-aided precise preparation of serial sections from small spheroids and visualization of marker molecules in 3D can provide a detailed overview of the cellular metabolic interplay in 3D cell culture models in cancer research and drug discovery.

cancer biology↗

bioRxiv2022

Bilateral JNK activation is a hallmark of interface contractility and promotes elimination of aberrant cells

Tissue-intrinsic defence mechanisms eliminate aberrant cells from epithelia and thereby maintain the health of developing tissues or adult organisms. Interface contractility comprises one such distinct mechanism that specifically guards against aberrant cells, which undergo inappropriate cell fate and differentiation programs. The cellular mechanisms which facilitate detection and elimination of these aberrant cells are currently unknown. We find that in Drosophila imaginal discs, interface contractility is associated with bilateral JNK activation at the clonal interface of wild type and aberrant cells. Bilateral JNK activation is unique to interface contractility and is not observed in other tissue-intrinsic defence mechanisms, such as cell-cell competition. We find that JNK is activated cell-autonomously by either of the contacting cell types and drives apoptotic elimination of cells at clonal interfaces. Ultimately, JNK interface signalling provides a collective tissue-level mechanism, which ensures elimination of aberrant, misspecified cells that cannot be identified by cell fitness criteria, as in cell-cell competition. Importantly, oncogenic Ras activates interface contractility but evades apoptotic elimination by bilateral JNK activation. Combined, our work establishes bilateral JNK interface signalling and interface apoptosis as a new hallmark of interface contractility, and it highlights how oncogenic mutations evade tumour suppressor function encoded by this tissue-intrinsic surveillance system.

developmental biology↗

bioRxiv2020

Making the invisible enemy visible

During the COVID-19 pandemic, structural biologists rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 204 previously solved structures from SARS-CoV-1, 548 structures covering 16 of the SARS-CoV-2 viral proteins have been released in a span of only 6 months. These structural models serve as the basis for research to understand how the virus hijacks human cells, for structure-based drug design, and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and may be even more common among these structures, which were solved quickly and under immense pressure. The Coronavirus Structural Task Force has responded to this challenge by rapidly categorizing, evaluating and reviewing all of these experimental protein structures in order to help downstream users and original authors. In addition, the Task Force provided improved models for key structures online, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge and others.

molecular biology↗