Biology subjects

Ziegler, P.

Publications and source records attributed to Ziegler, P..

7 recordsLinked to original sources

bioRxiv2025

Climate Change, Fisheries Management, and Increases in Demersal Fish Distribution in a Southern Ocean Biodiversity Hotspot

The worlds oceans and their biodiversity are undergoing going change driven by climate change and anthropogenic impacts such as fishing. The Kerguelen Plateau is a biodiversity hotspot with many endemic fish species, furthermore the region has economic importance in supporting valuable fisheries. This region is also a climate change hotspot with known notable changes in the location of the polar front, ocean currents, and primary productivity. In this study we use data from long-term scientific trawl surveys and contemporary joint species distribution models to understand how the demersal fish assemblage of the Kerguelen Plateau has changed through time and space. The modelling indicates that most demersal species have had notable changes in their occurrence and CPUE from 2003 to 2016. This included a significant increase in species richness throughout the study period. The modelling also provides novel insights into the depth, climatic and environmental preferences for all species, including many species that were previously data limited. It is unclear whether these changes reflect shifts in the fishery, management, or the effects of climate change, but most likely a combination of all. We also found evidence of several species distributions responding to temperature variability, with species being exposed to the ongoing impacts of climate change. This new information can be used by managers and policy makers to ensure continuation of sustainable fisheries and the protection of biodiversity into the future.

ecology↗

bioRxiv2024

Exploring mechanisms of change in a Southern Ocean fishery with a co-produced network model

A key challenge in planning long-term fisheries sustainability is overcoming uncertainties in predicted changes in target populations and catch rates in response to climate change and fishery trends. We combine transdisciplinary knowledge co-production and qualitative network modelling to advance system understanding and elucidate likely responses of a Patagonian toothfish fishery to future change. We co-developed a model of the Kerguelen Plateau biophysical-socioeconomic system with knowledge holders from industry and science; the first whole-of-system qualitative network model of intermediate complexity for this region. We present new approaches for dealing with uncertainty in network structure, and for investigating how perturbations propagate through a network. Using these tools, we found multiple potential pathways of decline for toothfish population and catch, but also some possible mechanisms of increase dependent on magnitude of certain effects. Our results highlight critical information gaps, including the potential role of scavenging benthos in fishery-ecosystem interactions and likely changes in the prey-field in response to warmer water, that require filling to improve predictions for toothfish populations and catch and forward planning for the fishery.

ecology↗

bioRxiv2024

Dissecting heterogeneity of tumor microenvironment in colorectal cancer using high-resolution single-cell atlas

The immune composition of the tumor microenvironment (TME) has a major impact on the therapeutic response and clinical outcome in patients with colorectal cancer (CRC). Here, we comprehensively characterize the TME at the single-cell level by first building a large-scale atlas that integrates 4.27 million single cells from 1,670 patient samples. We then complemented the atlas with single-cell profiles from four CRC cohorts with 266 patients, including cells with low mRNA content, spatial transcriptional profiles from 3.7 million cells, and protein profiles from 0.7 million cells. The analysis of the atlas allows refined tumor classification into four immune phenotypes: immune desert, B cell enriched, T cell enriched, and myeloid cell enriched subtypes. Within the myeloid compartment we uncover distinct subpopulations of neutrophils that acquire new functional properties in blood and in the TME, including anti-tumorigenic capabilities. Further, spatial multimodal single-cell profiling reveals that neutrophils are organized in clusters within distinct functional niches. Finally, using an orthotopic mouse model we show that cancer-derived systemic signals modify neutrophil production in the bone marrow, providing evidence for tumor-induced granulopoiesis. Our study provides a big data resource for the CRC and suggests novel therapeutic strategies targeting neutrophils.

bioinformatics↗

bioRxiv2023

Mitochondrial CISD1 is a downstream target that mediates PINK1 and Parkin loss-of-function phenotypes

Parkinsons disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain. Familial cases of PD are often caused by mutations of PTEN-induced kinase 1 (PINK1) and the ubiquitin ligase Parkin, both pivotal in maintaining mitochondrial quality control. CISD1, a homodimeric mitochondrial iron-sulfur-binding protein, is a major target of Parkin-mediated ubiquitination. We here discovered a heightened propensity of CISD1 to form dimers in Pink1 mutant flies and in dopaminergic neurons from PINK1 mutation patients. The dimer consists of two monomers that are covalently linked by a disulfide bridge. In this conformation CISD1 cannot coordinate the iron-sulfur cofactor. Overexpressing Cisd, the Drosophila orthologue of CISD1, and a mutant Cisd incapable of binding the iron-sulfur cluster in Drosophila reduced climbing ability and lifespan. This was more pronounced with mutant Cisd and aggravated in Pink1 mutant flies. Complete loss of Cisd, in contrast, rescued all detrimental effects of Pink1 mutation on climbing ability, wing posture, dopamine levels, lifespan, and mitochondrial ultrastructure. Our results suggest that Cisd, probably iron-depleted Cisd, operates downstream of Pink1 shedding light on PD pathophysiology and implicating CISD1 as a potential therapeutic target.

neuroscience↗

bioRxiv2021

Dissecting CD8+ T cell pathology of severe SARS-CoV-2 infection by single-cell epitope mapping

The current COVID-19 pandemic represents a global challenge. A better understanding of the immune response against SARS-CoV-2 is key to unveil the differences in disease severity and to develop future vaccines targeting novel SARS-CoV-2 variants. Feature barcode technology combined with CITE-seq antibodies and DNA-barcoded peptide-MHC I Dextramer reagents enabled us to identify relevant SARS-CoV-2-derived epitopes and compare epitope-specific CD8+ T cell populations between mild and severe COVID-19. We identified a strong CD8+ T cell response against an S protein-derived epitope. CD8+ effector cells in severe COVID-19 displayed hyperactivation, T cell exhaustion and were missing characteristics of long-lived memory T cells. We identify A*0101 WTAGAAAYY as an immunogenic CD8+ T cell epitope with the ability to drive clonal expansion. We provide an in-depth characterization of the CD8+ T cell-mediated response to SARS-CoV-2 infection which will be relevant for the development of molecular and targeted therapies and potential adjustments of vaccination strategies.

immunology↗

bioRxiv2021

Alpha-arrestins Aly1 and Aly2 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis

Phosphatidylinositol (PI) is an essential phospholipid and critical component of membrane bilayers. The complete deacylation of PI by phospholipases of the B-type leads to the production of intracellular and extracellular glycerophosphoinositol (GPI), a water-soluble glycerophosphodiester. Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters that resides at the plasma membrane in yeast. Once internalized, GPI can be degraded to produce inositol, phosphate and glycerol, thereby contributing to reserves of these building blocks. Not surprisingly, GIT1 gene expression is controlled by nutrient balance, with limitation for phosphate or inositol each increasing GIT1 expression to facilitate GPI uptake. Less is known about how Git1 protein levels or localization are controlled. Here we show that the -arrestins, an important class of protein trafficking adaptor, regulate the localization of Git1 in a manner dependent upon their association with the ubiquitin ligase Rsp5. Specifically, -arrestin Aly2 is needed for effective Git1 internalization from the plasma membrane under basal conditions. However, in response to GPI-treatment of cells, either Aly1 or Aly2 can promote Git1 trafficking to the vacuole. Retention of Git1 at the cell surface, as occurs in aly1{Delta} aly2{Delta} cells, results in impaired growth in the presences of excess exogenous GPI and results in increased uptake of radiolabeled GPI, suggesting that accumulation of this metabolite or its downstream products leads to cellular toxicity. We further show that regulation of -arrestin Aly1 by the protein phosphatase calcineurin improves both steady-state and ligand-induced trafficking of Git1 when a mutant allele of Aly1 that mimics the dephosphorylated state at calcineurin-regulated residues is employed. Thus, calcineurin regulation of Aly1 is important for the GPI-ligand induced trafficking of Git1 by this -arrestin, however, the role of calcineurin in regulating Git1 trafficking is much broader than can simply be explained by regulation of the -arrestins. Finally, we find that loss of Aly1 and Aly2 leads to an increase in phosphatidylinositol-3-phosphate on the limiting membrane of the vacuole and this alteration is further exacerbated by addition of GPI, suggesting that the effect is at least partially linked to Git1 function. Indeed, loss of Aly1 and Aly2 leads to increased incorporation of inositol label from 3H-inositol-labelled GPI into PI, confirming that internalized GPI influences PI synthesis and indicating a role for the -arrestins in regulating the process.

cell biology↗

bioRxiv2020

A three-dimensional Air-Liquid Interface Culture Model for the Study of Epstein-Barr virus Infection in the Nasopharynx

Epstein-Barr virus (EBV) infection is ubiquitous in humans and is associated with the cancer, nasopharyngeal carcinoma. EBV replicates in the differentiated layers of stratified keratinocytes but whether the other cell types of the airway epithelium are susceptible to EBV is unknown. Here, we demonstrate with primary nasopharyngeal cells grown at the air-liquid interface that the pseudostratified epithelium can be susceptible to EBV infection and we report that susceptible cell types with distinct EBV transcription profiles can be identified by single-cell RNA-sequencing. Although EBV infection in the nasopharynx has evaded detection in asymptomatic carriers, these findings demonstrate that EBV latent and lytic infection can occur in the cells of the nasopharyngeal epithelium.

microbiology↗