Biology subjects

Goebel, M.

Publications and source records attributed to Goebel, M..

6 recordsLinked to original sources

bioRxiv2025

Systemic and local regulation of root growth by vascular trehalose 6-phosphate is correlated with re-allocation of primary metabolites between shoots and roots

Trehalose 6-phoshpate (Tre6P) is a key signalling molecule that reflects carbon status and integrates it with developmental decision making. Tre6P has been demonstrated to regulate various developmental processes, including vegetative growth, shoot branching, flowering, and root branching. Here, we investigate how vasculature-derived Tre6P influences root system architecture by expressing heterologous Tre6P synthase (TPS) or Tre6P phosphatase (TPP) specifically in the plant vasculature. Plants with elevated vascular-derived Tre6P levels had smaller root systems, reduced sucrose levels, and lower root metabolite levels, whereas vascular TPP overexpression had the opposite effect. Using reciprocal grafting experiments, we identified shoot-derived vascular Tre6P to be the main driver of these systemic responses. In lines with increased Tre6P in the shoot vasculature, the shoot-to-root metabolite ratios were consistently increased, indicating that Tre6P modulates metabolite allocation and utilization to balance carbon partitioning between shoot and root growth. Our data further suggest that vascular Tre6P contributed to optimizing the carbon-to-nitrogen ratio to support growth and fitness. Besides this systemic function, this study shows that root-derived Tre6P also plays a critical local role in modulating root development. Collectively, our results demonstrate that Tre6P in the vasculature functions both systemically and locally to coordinate metabolic status with root growth and architecture.

plant biology↗

bioRxiv2025

Peroxisome protein import deficiency causes heart failure in mouse and human

Peroxisomes are ubiquitous cellular organelles with potentially vital roles in lipid and reactive oxygen metabolism. The metabolic demands of the heart are substantial; however, the contribution of peroxisomes to cardiac development, health, and their role in heart failure (HF) remain largely unexplored. We developed and examined a mouse and an engineered human myocardium (EHM) model with a deficiency in cardiac peroxisome biogenesis to investigate the role of peroxisomes in cardiac function and pathology. In the EHM, loss of peroxisome protein import and subsequent peroxisomal metabolic impairment trigger mitochondrial damage and compromise cellular respiration and energy production. Peroxisome dysfunction results in incoherent electrical conduction, defective Ca2+-handling, and ultimately presentation of a HF phenotype with pathological force generation. These phenotypes are mirrored in an orthogonal murine model system with defective cardiac peroxisome biogenesis. Preload-dependent deficits in force generation due to insufficient energy supply are eventually fatal. Thus, peroxisomes play an important role in sustaining normal heart operations. Vice versa, peroxisome maintenance is compromised in pressure overload-induced HF, establishing peroxisomes as potential modulators of pathology and targets of therapy.

cell biology↗

bioRxiv2024

Accessing the specific capacity of TIL-derived CD8 T-cells to suppress tumor recurrence in resectable HBV-HCC patients

BackgroundHepatocellular carcinoma represents a significant global health challenge, affecting over a million patients annually, arising mainly from chronic liver diseases, with a majority being related to viral infections. However, despite the groundbreaking clinical results of immune checkpoint blockades and adoptive cell therapies, we still face non-responders accompanied by high rebound rates after resection. Considering that the main concern is to overcome a highly specialized immunosuppressive tumor microenvironment of the individual patient, the characterization of the particular tumor microenvironment and the source of the immune cells used in ACT is of immense importance. Approved ACT therapies mainly use modified peripheral blood cells from individuals. At the same time, tumor-infiltrating lymphocytes are underrepresented even if they have garnered interest due to their potential to target tumor-specific antigens more effectively. MethodsIn this study, we employed allogenic and autologous immune cell sources for expansion and stimulation, resulting in adoptive T-cell transfer experiments determining the effector cell differentiation and the related anti-tumor effects by the possible implementation of re-stimulation. ResultsWe determined a high success rate in expanding and stimulating tumor-infiltrating lymphocytes with consistent CD8 T-cell fractions from HCC patients. To showcase the effectiveness of stimulated T-cells from different sources, we generated cell lines derived from the margin and center of an HBV-induced HCC with a highly immune-suppressive TME. We found effective immune responses supported by cell death induction, ferroptosis, proptosis and apoptosis triggered by all sources of T-cells depending on the area of derived tumor cells. ConclusionEffector T-cell fractions derived from tumor-infiltrating lymphocytes present a viable source for cell-based immune therapy combined with immune checkpoint inhibitors in HCC patients, especially after resection, to suppress rebound strategies of the parental tumor on an individual level.

immunology↗

bioRxiv2024

Patient-derived HCC cells recapitulating the transcriptomic landscape of primary HCV-related liver cancer

BackgroundThe hepatocellular carcinoma is one of the leading causes of cancer-related mortality and is characterized by high heterogeneity and subsequently adaptation by developing resistance to current treatments. In this scenario the application of individualized models is crucial to understand the potential of approved therapies. Recently, we established a series of individual cell lines derived from patients who developed HCC on different entities, serving as a platform for individual approaches. In this study, we classified the LC4 cells derived from the center region of a HCC with underlying HIV-HCV co-infection, by using deep analysis on the pathway regulation level. MethodsWe employed DEG analysis, followed by pathway analysis to characterize the preservation level of the LC4 cells and the level of adoption. Next, we classify the model, by employing healthy donor samples, commonly used HCC cell lines and global RNAseq data sets. ResultsWe showed that the LC4 cells reflect significant characteristics of the parental region, including the replication of the immuno-suppressive and the proliferative milieu. The LC4 cells exhibit a metabolic reprogramming characterized by the downregulation of drug-metabolizing CYP enzymes compared to healthy individuals, indicating a transition to alternate metabolic pathways. Moreover, we identified common Biomarkers in the parental tissue, global datasets and the LC4 cells. ConclusionWe showed that the LC4 cell line is applicable as an individual model for pre-clinical testing of treatment regimens in HCC driven research.

cancer biology↗

bioRxiv2021

Automatic Detection and Neurotransmitter Prediction of Synapses in Electron Microscopy

This paper presents a deep-learning based workflow to detect synapses and predict their neurotransmitter type in the primitive chordate Ciona intestinalis (Ciona) EM images. Identifying synapses from electron microscopy (EM) images to build a full map of connections between neurons is a labor-intensive process and requires significant domain expertise. Automation of synapse detection and classification would hasten the generation and analysis of connectomes. Furthermore, inferences concerning neuron type and function from synapse features are in many cases difficult to make. Finding the connection between synapse structure and function is an important step in fully understanding a connectome. Activation maps derived from the convolutional neural network provide insights on important features of synapses based on cell type and function. The main contribution of this work is in the differentiation of synapses by neurotransmitter type through the structural information in their EM images. This enables prediction of neurotransmitter types for neurons in Ciona which were previously unknown. The prediction model with code is available on Github.

neuroscience↗

bioRxiv2019

Integrative functional genomics decodes herpes simplex virus 1

Since the genome of herpes simplex virus 1 (HSV-1) was first sequenced more than 30 years ago, its predicted 80 genes have been intensively studied. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identified a total of 201 viral transcripts and 284 open reading frames (ORFs) including all known and 46 novel large ORFs. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of novel viral ORFs as well as N-terminal extensions (NTEs) and truncations thereof. We show that key viral regulators and structural proteins possess NTEs, which initiate from non-canonical start codons and govern subcellular protein localization and packaging. We validated a novel non-canonical large spliced ORF in the ICP0 locus and identified a 93 aa ORF overlapping ICP34.5 that is thus also deleted in the FDA-approved oncolytic virus Imlygic. Finally, we extend the current nomenclature to include all novel viral gene products. Taken together, this work provides a valuable resource for future functional studies, vaccine design and oncolytic therapies.

microbiology↗