Biology subjects

Visser, F.

Publications and source records attributed to Visser, F..

6 recordsLinked to original sources

bioRxiv2025

A sensitive orange fluorescent calcium ion indicator for imaging neural activity

Genetically encoded calcium indicators (GECIs) are vital tools for fluorescence-based visualization of neuronal activity with high spatial and temporal resolution. However, current highest-performance GECIs are predominantly green or red fluorescent, limiting multiplexing options and efficient excitation with fixed-wavelength femtosecond lasers operating at 1030 nm. Here, we introduce OCaMP (also known as O-GECO2), an orange fluorescent GECI engineered from O-GECO1 through targeted substitutions to improve calcium affinity while retaining the favorable photophysical properties of mOrange2. OCaMP exhibits improved two-photon cross-section, responsiveness, photostability, and calcium affinity relative to O-GECO1. In cultured neurons, zebrafish, and mouse cortex, OCaMP outperforms the red GECIs jRCaMP1a and jRGECO1a in sensitivity, kinetics, and signal-to-noise ratio. These properties establish OCaMP as a robust tool for high-fidelity neural imaging optimized for 1030 nm excitation and a compromise-free option within the spectral gap between existing green and red GECIs.

neuroscience↗

bioRxiv2024

Population regulation in semelparous deep-sea squid is driven by ecological conditions in surface waters and whale predation at depth

Predator-prey interactions present a powerful framework for understanding population regulation in natural systems, including the vast and understudied pelagic deep sea. Oceanic squid are among the most abundant and important species groups in this habitat and function as primary prey for the largest marine top predators, deep-diving cetaceans. At the same time, these cryptic animals are highly data deficient. Insight into the dynamics of deep-sea squid populations and the impacts of predation by top-predators is crucial for designing conservation strategies and developing a general theory of deep-sea ecology. Here, we offer fundamental new insights into how individual life history and predation interact to shape population regulation in deep-sea squid. Using empirical data, we develop a size-structured population model for a highly abundant histioteuthid deep-sea squid. We show that population regulation is driven primarily by conditions experienced as paralarvae in the upper water column, where they face intense resource competition. Relaxation of this competition following ontogenetic migration as juveniles drives exponential-like growth curves. Population dynamics exhibit single-cohort cycles, producing regular seasonal patterns in reproduction, even in the absence of any environmental seasonality. Furthermore, we demonstrate that predation by deep-diving cetaceans at different depths can lead to emergent facilitation between top predators. This reveals the complex interdependencies in trophic networks connecting the deep sea with surface waters. Our findings provide critical insights into the ecological functioning of the pelagic deep-sea and their link with surface waters. These insights are urgently needed to better understand and conserve this vast, data-deficient habitat, which endangered deep-diving predators depend on but is under major stress from anthropogenic activities.

ecology↗

bioRxiv2024

The Pannexin-1 N-terminal Helix Gates a Switch between Ion Conductance and Anandamide Transport

Anandamide is an endovanilloid and endocannabinoid with ligand activity at transient receptor potential vanilloid 1 channels and cannabinoid receptors, respectively. We have reported that block of Pannexin-1 channels in the CA1 hippocampus can increase concentrations of anandamide and induce presynaptic plasticity. It is not known how an ion channel can contribute to clearance of a lipid-derived signalling molecule. Here, we use electrophysiology and imaging of uptake of fluorescent anandamide to determine the structure-function relationship between the ion conduction and anandamide trasporter activities of pannexin-1. Expression of rat, mouse or human pannexin-1 in HEK cells caused a time dependent increase in anandamide uptake by all three orthologs. However, human pannexin-1 had reduced ion conduction. Low concentrations of anandamide augmented uptake of its fluorescent derivative, whereas higher concentrations competed, suggesting that anadamide may facilitate its own transport. Deletion of the N-terminal helix of pannexin-1 and the channel blocker, probenecid, blocked ion conduction but enhanced anandamide transport. In contrast, mutation of pore facing isoleucine 41 caused a gain of function in ion conduction with loss of anandamide transport. We conclude that the pannexin-1 channel is a dual ion channel / anandamide transporter and that these properties are gated by the channels N-terminal helix and likely linked to its presence or absence within the pore lining region.

neuroscience↗

bioRxiv2023

Spatially resolved single-cell analysis uncovers protein kinase C-& expressing microglia with anti-tumor activity in glioblastoma

Glioblastoma (GBM) is a brain tumor that poses a formidable challenge to treatment options available. The tumor microenvironment (TME) in GBM is highly complex, marked by immunosuppression and cellular heterogeneity. Understanding the cellular interactions and their spatial organization within the TME is crucial for developing effective therapeutic strategies. In this study, we integrated single-cell RNA sequencing and spatial transcriptomics in a GBM mouse model to unravel the spatial landscape of the brain TME. We identified a previously unrecognized microglia subtype expressing protein kinase C{delta} (PKC{delta}) associated with potent anti-tumor functions. The presence of PKC{delta}-expressing microglia was confirmed in resected human GBM specimens. Elevating tumoral PKC{delta} expression using niacin or adeno-associated virus in mice enhanced the phagocytosis of GBM cells by microglia in culture and increased the lifespan of mice with intracranial GBM. These findings were corroborated in analyses of the TCGA GBM datasets where low PKC{delta} samples showed negative pathway enrichment for apoptosis, phagocytosis, and immune signaling pathways, as well as lower levels of immune cell infiltration overall. Our study underscores the importance of integrating spatial context to unravel the TME, resulting in the identification of previously unrecognized subsets of microglia with anti-tumor functions. These findings provide valuable insights for advancing innovative immunotherapeutic strategies in GBM.

immunology↗

bioRxiv2022

Single cell spatial analysis identifies regulators of brain tumor initiating cells

Glioblastomas (GBMs) are aggressive brain tumors with extensive intratumoral heterogeneity. Here, we used spatial transcriptomics and single-cell ATAC-seq to dissect the transcriptome of distinct anatomical regions of the tumor microenvironment. We identified numerous extracellular matrix (ECM) molecules including biglycan elevated in areas infiltrated with brain tumor-initiating cells (BTICs). Single-cell RNA sequencing showed that the ECM molecules were differentially expressed by cells including injury response versus developmental BTICs. Exogeneous biglycan or overexpression of biglycan resulted in a higher proliferation rate of BTICs, and this was associated mechanistically with LDL receptor-related protein 6 (LRP6) binding and activation of the Wnt/{beta}-catenin pathway. Biglycan-overexpressing BTICs grew to a larger tumor mass when implanted intracranially in mice. This study points to the spatial heterogeneity of ECM molecules in the GBM microenvironment and suggests biglycan-LRP6 axis as a therapeutic target to curb GBM growth.

cancer biology↗

bioRxiv2018

Beaked and killer whales show how collective prey behaviour foils acoustic predators

Animals aggregate to obtain a range of fitness benefits, but a common cost of aggregation is increased detection by predators. Here we show that, in contrast to visual and chemical signallers, aggregated acoustic signallers need not face higher predator encounter rate. This is the case for prey groups that synchronize vocal behaviour but have negligible signal time-overlap in their vocalizations. Beaked whales tagged with sound and movement loggers exemplify this scenario: they precisely synchronize group vocal and diving activity but produce non-overlapping short acoustic cues. They combine this with acoustic hiding when within reach of eavesdropping predators to effectively annul the cost of aggregation for predation risk from their main predator, the killer whale. We generalize this finding in a mathematical model that predicts the key parameters that social vocal prey, which are widespread across taxa and ecosystems, can use to mitigate detection by eavesdropping predators.

ecology↗