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Biology subjects

Binder, B.

Publications and source records attributed to Binder, B..

6 recordsLinked to original sources

Analysing diffusion limited processes in a cylinder using pair-correlation functions

Diffusion-limited processes (DLP) are found in various physical, biological, and engineering systems, yet their quantification within complex spatial domains remains a challenge. In this study, we develop novel one-dimensional non-periodic and periodic pair-correlation functions (PCF) to assess the spatial patterns of DLP within a cylindrical domain. By refining previous PCF formulations, we introduce an efficient binning-based approach that significantly reduces computational costs, making the method feasible for large-scale simulations. Our analysis provides a comprehensive examination of PCF variability, distinguishing between global deviations from complete spatial randomness state and sampling-induced variation. An off-lattice agent-based model is implemented, successfully reproducing self-organized patterns reminiscent of classical DLP studies and aligning with fractal-like aggregation behaviours. We demonstrate the utility of periodic PCFs in capturing key spatial correlations in DLP, particularly in azimuthal and Cartesian projections, while highlighting the conditions under which non-periodic PCFs remain preferable. Our findings underscore the potential of PCFs as robust summary statistics for complex spatial models, with applications ranging from microbial colony formation and blood clotting dynamics to image analysis and classification algorithms.

biophysics↗

Accidental and Regulated Cell Death in Yeast Colony Biofilms

The yeast species Saccharomyces cerevisiae is one of the most intensively studied organisms on the planet due to being an excellent eukaryotic model organism in molecular and cell biology. In this work, we investigate the growth and morphology of yeast colony biofilms, where proliferating yeast cells reside within a self-produced extracellular matrix. This research area has garnered significant scientific interest due to its applicability in the biological and biomedical sectors. A central feature of yeast colony biofilm expansion is cellular demise, which is onset by one of two independent mechanisms: either accidental cell death (ACD) or regulated cell death (RCD). In this article, we generalise a recently developed continuum model for the nutrient-limited growth of a yeast colony biofilm to include the effects of ACD and RCD. This new model involves a system of four coupled nonlinear reaction-diffusion equations for the yeast-cell density, the nutrient concentration, and two species of dead cells. Numerical solutions of the spatially one and two-dimensional governing equations reveal the impact that ACD and RCD have on expansion speed, morphology and cell distribution within the colony biofilm. Our results show good qualitative agreement with our own experiments.

microbiology↗

An off-lattice discrete model to characterise filamentous yeast colony morphology

We combine an off-lattice agent-based mathematical model and experimentation to explore filamentous growth of a yeast colony. Under environmental stress, Saccharomyces cerevisiae yeast cells can transition from a bipolar (sated) to unipolar (pseudohyphal) budding mechanism, where cells elongate and bud end-to-end. This budding asymmetry yields spatially non-uniform growth, where filaments extend away from the colony centre, foraging for food. We use approximate Bayesian computation to quantify how individual cell budding mechanisms give rise to spatial patterns observed in experiments. We apply this method of parameter inference to experimental images of colonies of two strains of S. cerevisiae, in low and high nutrient environments. The initial nutrient concentration and a forking mechanism for pseudohyphal cell proliferation are the key features driving colony morphology. Simulations run with the most likely inferred parameters produce colony morphologies that closely resemble experimental results.

cell biology↗

Ethylene Receptor Gain- and Loss-of-function Mutants Reveal an ETR1-dependent Transcriptional Network in Roots

In Arabidopsis, a family of five receptors mediates ethylene responses in roots, with Ethylene Response 1 (ETR1) controlling increases in root hair proliferation and decreases in lateral root formation. To define the ETR1-dependent gene regulatory network (GRN) controlling root development, we profiled the root transcriptome from Col-0 and the etr1-3 gain-of-function and etr1-7 loss-of-function mutants in the presence and absence of ethylene or the ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC). We identified 4,522 differentially expressed (DE) transcripts in Col-0 roots with altered abundance in response to ethylene and/or ACC treatment, with larger magnitude changes induced by ethylene. These included 553 DE transcripts that were ETR1 dependent, defined by a lack of response to treatment with ethylene and/or ACC in ethylene-insensitive etr1-3 and constitutively altered in etr1-7 in the presence and absence of treatment relative to time-0 Col-0. Within these ETR1-dependent transcripts were ethylene biosynthesis genes and transcription factors. ACC OXIDASE 2 (ACO2) and ACO3 convert ACC to ethylene and were ETR1-dependent, and ACO-promoter-driven reporter fusions were ACC regulated in root tissues in appropriate locations to control root development, with ACO5 localized to root hairs. Abundance of ETR1-dependent transcripts that were predicted to encode transcription factors and ACOs were examined in Col-0 and an ein3eil1 mutant with and without ACC treatment, suggesting the ETR1 and EIN3/EIL1 canonical ethylene signaling pathway regulated some, but not all, of these transcriptional responses. Together, these findings reveal features of an ETR1-dependent GRN that controls both ethylene synthesis and root growth and development. One sentence summaryTranscriptional responses in etr1 LOF and GOF mutants reveal an ethylene-mediated ETR1- and EIN3 dependent gene regulatory network that modulates ethylene signaling and synthesis and root development.

plant biology↗

The Plasminogen-Apple-Nematode (PAN) domain suppresses JA/ET defense pathways in plants

Suppression of immune response is a phenomenon that enables biological processes such as gamete fertilization, cell growth, cell proliferation, endophyte recruitment, parasitism, and pathogenesis. Here, we show for the first time that the Plasminogen-Apple-Nematode (PAN) domain present in G-type lectin receptor-like kinases is essential for immunosuppression in plants. Defense pathways involving jasmonic acid and ethylene are critical for plant immunity against microbes, necrotrophic pathogens, parasites, and insects. Using two Salix purpurea G-type lectin receptor kinases, we demonstrated that intact PAN domains suppress jasmonic acid and ethylene signaling in Arabidopsis and tobacco. Variants of the same receptors with mutated residues in this domain could trigger induction of both defense pathways. Assessment of signaling processes revealed significant differences between receptors with intact and mutated PAN domain in MAPK phosphorylation, global transcriptional reprogramming, induction of downstream signaling components, hormone biosynthesis and resistance to Botrytis cinerea. Further, we demonstrated that the domain is required for oligomerization, ubiquitination, and proteolytic degradation of these receptors. These processes were completely disrupted when conserved residues in the domain were mutated. Additionally, we have tested the hypothesis in recently characterized Arabidopsis mutant which has predicted PAN domain and negatively regulates plant immunity against root nematodes. ern1.1 mutant complemented with mutated PAN shows triggered immune response with elevated WRKY33 expression, hyperphosphorylation of MAPK and resistant to necrotrophic fungus Botrytis cinerea. Collectively, our results suggest that ubiquitination and proteolytic degradation mediated by the PAN domain plays a role in receptor turn-over to suppress jasmonic acid and ethylene defense signaling in plants.

plant biology↗

Ex vivo detection of SARS-CoV-2-specific CD8+ T cells: rapid induction, prolonged contraction, and formation of functional memory

CD8+ T cells are critical for the elimination and long-lasting protection of many viral infections, but their role in the current SARS-CoV-2 pandemic is unclear. Emerging data indicates that SARS-CoV-2-specific CD8+ T cells are detectable in the majority of individuals recovering from SARS-CoV-2 infection. However, optimal virus-specific epitopes, the role of pre-existing heterologous immunity as well as their kinetics and differentiation program during disease control have not been defined in detail. Here, we show that both pre-existing and newly induced SARS-CoV-2-specific CD8+ T-cell responses are potentially important determinants of immune protection in mild SARS-CoV-2 infection. In particular, our results can be summarized as follows: First, immunodominant SARS-CoV-2-specific CD8+ T-cell epitopes are targeted in the majority of individuals with convalescent SARS-CoV-2 infection. Second, MHC class I tetramer analyses revealed the emergence of phenotypically diverse and functionally competent pre-existing and newly induced SARS-CoV-2-specific memory CD8+ T cells that showed similar characteristics compared to influenza-specific CD8+ T cells. Third, SARS-CoV-2-specific CD8+ T-cell responses are more robustly detectable than antibodies against the SARS-CoV-2-spike protein. This was confirmed in a longitudinal analysis of acute-resolving infection that demonstrated rapid induction of the SARS-CoV-2-specific CD8+ T cells within a week followed by a prolonged contraction phase that outlasted the waning humoral immune response indicating that CD8+ T-cell responses might serve as a more precise correlate of antiviral immunity than antibody measurements after convalescence. Collectively, these data provide new insights into the fine specificity, heterogeneity, and dynamics of SARS-CoV-2-specific memory CD8+ T cells, potentially informing the rational development of a protective vaccine against SARS-CoV-2.

immunology↗