Biology subjects

Renz, M.

Publications and source records attributed to Renz, M..

5 recordsLinked to original sources

bioRxiv2025

Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits

All cells in an animal collectively ensure, moment-to-moment, the survival of the whole organism in the face of environmental stressors1,2. Physiology seeks to elucidate the intricate network of interactions that sustain life, which often span multiple organs, cell types, and timescales, but a major challenge lies in the inability to simultaneously record time-varying cellular activity throughout the entire body. We developed WHOLISTIC (WHole Organism Live Imaging System for recording Tissue and IntraCellular activity), a method to image second-timescale, time-varying intracellular dynamics across cell-types of the vertebrate body. By advancing and integrating volumetric fluorescence microscopy, machine learning, and pancellular transgenic expression of calcium sensors in transparent young Danio rerio (zebrafish) and with proof of concept in adult Danionella, the method enables real-time recording of cellular dynamics across the organism. Calcium is a universal intracellular messenger, with a large array of cellular processes depending on changes in calcium concentration across varying time-scales, making it an ideal proxy of cellular activity3. Using this platform to screen the dynamics of most cells in the body, we discovered unexpected responses of specific cell types to stimuli, such as chondrocyte reactions to cold, meningeal responses to ketamine, and state-dependent activity, such as oscillatory ependymal-cell activity during periods of extended motor quiescence. At the organ scale, the method uncovered pulsating traveling waves along the kidney nephron. At the multi-organ scale, we uncovered muscle synergies and independencies, as well as muscle-organ interactions. Integration with optogenetics allowed us to all-optically determine the causal direction of brain-body interactions. At the whole-organism scale, the method captured the rapid brainstem-controlled redistribution of blood flow across the body. Finally, we advanced Whole-Body Expansion Microscopy4 to provide ground-truth molecular and ultrastructural anatomical context, explaining the spatiotemporal structure of activity captured by WHOLISTIC. Together, these innovations establish a new paradigm for systems biology, bridging cellular and organismal physiology, with broad implications for both fundamental research and drug discovery.

neuroscience↗

bioRxiv2024

Development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes

IntroductionThe endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins, which constitute a large fraction of the total protein output of a mammalian cell. Striated muscle cells contain a specialized membrane system known as the sarcoplasmic reticulum (SR) that controls calcium homeoastasis and contraction, however the biochemical and physiological relationship between the ER and SR and how both compartments participate in protein synthesis remains incompletely understood. MethodsProtein quantification and imaging of selected marker proteins for ER and SR functions was performed to characterize the relationship of the ER and SR and its individual involvement in protein synthesis in neonatal and adult cardiac myocytes. Superresolution microscopy was used to examine the interaction of ribosomes and the SR in adult cardiac myocytes. ResultsQuantification of ER and SR-associated proteins of isolated ventricular cardiac myocytes showed that relative expression of ER/SR resident protein quality elements, as well as relative ribosome levels are decreased in adult cells, whereas SR-associated Ca2+ handling proteins increase. Immunocytoflourescence revealed that the membrane compartment that exists in early postpartum resembles mostly the ER and decreases in postnatal development. The SR is the main membrane network that exists in the adult cardiac myocytes, replacing the ER, in all but the perinuclear region. Immunocytoflourescence staining further indicated that both networks perform overlapping but distinct, specialized functions, such as localization of excitation-contraction coupling exclusively to the SR or initiation of secretion via the classical secretory pathway mainly from the ER. Ribosomes and mRNA were localized both in close proximity to the ER and the SR of adult ventricular cardiac myocytes. Superresolution microscopy confirmed that both the ER as well as the developed SR bind ribosomes and are direct sites of protein synthesis and protein homeostasis in adult cardiac myocytes. ConclusionOur findings suggest molecular differentiation and structural organization of the ER/SR in cardiac muscle development, resulting in the development of a protein synthesis network at the sarco/endoplasmic reticulum in adult cardiac myocytes.

cell biology↗

bioRxiv2023

Repeated FRAP of the actin-binding protein CapG in the cell nucleus - a functional assay for EGF signaling in the single live breast cancer cell

Compartmentalization and differential distribution of proteins within a cell maintain cellular function and viability. CapG is the only gelsolin-related actin-binding protein that distributes in steady state diffusively throughout cytoplasm and cell nucleus. To detect changes in CapGs nuclear shuttling in response to external stimuli on the single cell level, we established repeated FRAP experiments of one and the same breast cancer cell. With this experimental set up, we found that ATP-depletion reversibly decreased CapGs shuttling into the cell nucleus. The addition of epidermal growth factor (EGF) increased CapGs nuclear shuttling within minutes. Serum-starvation doubled the number of breast cancer cells from 40% to 80% displaying increased CapG shuttling in response to EGF. Testing five different potential CapG phosphorylation sites, we found that serine 70 mediates the increase in CapGs nuclear shuttling triggered by EGF. Thus, repeated FRAP of CapG in the cell nucleus can be used as functional readout of signaling cascades in the same single live breast cancer cell.

cancer biology↗

bioRxiv2022

Thirty years of deforestation within the entire ranges of nine endangered lemur species (3 CR, 4 EN, 2 VU) in northwestern Madagascar

Forest cover change is of particular concern in tropical regions. In this study, we investigate the degree of deforestation in the entire ranges of nine highly threatened lemur species in northwestern Madagascar. Landsat satellite images were acquired from four different time stages (1990, 2000, 2011, 2020), classified into forest/non-forest, and changes quantified. Forest cover declined from 17.5% to 9.3% within the last 30 years. This decline varied across four protected areas (PAs) investigated: the forest cover of Ankarafantsika National Park (ANP) declined only moderately over time (from 76.3% to 67.4%), while it declined drastically in other PAs (e.g., from 54.9% to 18.9%, Bongolava Forest Corridor). Two lemur taxa are most affected (Lepilemur otto, Microcebus bongolavensis) by having only very few isolated forest patches left within their ranges (approximately 542.7 km{superscript 2}). For two other species (L. ahmansoni, L. aeeclis), most of the remaining forest is concentrated in two coastal PAs (in total 627.2 and 477.9 km{superscript 2}, respectively), while those species occurring inside ANP (5 taxa) experienced rather stable forest coverage until 2020. A reversal of these deforestation trends and active reforestation measures are desperately needed to reduce habitat loss for these nine lemur species. A practical experience-based guideline is therefore provided.

ecology↗

bioRxiv2018

Cytoplasmic self-organization established by internal lipid membranes in the interplay with either actin or microtubules

Cells harbor an intrinsic organization of their components. Specific protein structures, as the centrosome, have been described master regulators of cell organization. In the absence of these key elements, however, cytoplasmic selforganization has nevertheless been observed. Cytoplasmic self-organization was postulated to arise from the interaction of microtubules with molecular motors on lipid membrane surfaces.\n\nHere, we show that lipid membranes are capable of organizing both major cytoskeletal systems, microtubules and actin, even if one or the other cytoskeletal system is completely paralyzed. A microfluidic droplet system and Xenopus oocyte extracts enabled us to build an artificial cell and study minimal requirements for cellular self-organization. Mathematical modeling reveals the interaction of lipid membranes with any filament system through molecular motors as a universal principle of cytoplasmic self-organization. Both cytoskeletal systems form mechanisms to establish robust 2-dimensional selforganization and self-centering. Pharmacologic inhibition of the cytoskeletal network systems helps dissect specific contributions of each network in the interplay with lipid membranes with regards to 2- and 3-dimensional organization, time and length scale of cytoplasmic organization and the degree of concentration of the centered elements. While microtubules provide 3-dimensional polarity, actin filaments ensure fast and dense compaction and long-range organization.

cell biology↗