Biology subjects

Panconi, L.

Publications and source records attributed to Panconi, L..

3 recordsLinked to original sources

bioRxiv2025

Nanoscale protein clustering modulates the input-output response of cellular signalling pathways

A key function of the plasma membrane is regulating signal transduction. Proteins involved in the transduction process play a signal-processing role; mapping an input (e.g. number of engaged receptors) to an output (e.g. level of downstream phosphorylation). In many cases, a digital mapping is desirable, i.e. that a cell activates or responds fully once a set input threshold is surpassed. It is believed that the nanoscale organisation of proteins, such as their clustering, modulates this behaviour by altering the frequency of protein-protein interactions. Here, we develop a generalised simulator for dynamic molecular clustering built around agent-based modelling. We show that the clustering properties (e.g. size of clusters, percentage of monomers) tunes the cellular response. This work paves the way for designing potential therapeutic interventions that alter the nanoscale patterning of molecules on the cell surface in order to alter cell behaviour. AUTHOR SUMMARYSignal transduction is the process by which cells convert external signals into internal responses. This is essential for such functions as hormone signalling and immunity. Many membrane proteins form nanoscale clusters on the cell surface, and state-of-the-art imaging methods allow us to see these clusters in detail. We developed an agent-based simulator to explore how clustering of key signaling proteins (such as kinases and phosphatases) can influence cell signalling outputs. Our results suggest that protein clustering can "digitize" signals, pushing cells to respond in an "all-or-nothing" manner, rather than producing a smooth range of responses. This research contributes to a broader understanding of how dynamic reorganization of transmembrane proteins contributes to information processing. This is a central question in systems biology, with relevance to the fields of immunology, neuroscience, and cancer. By highlighting how the geometric properties of protein distributions can alter signalling responses, we may identify novel methods to manipulate cell behavior.

systems biology↗

bioRxiv2022

Phospholipid tail asymmetry allows cellular adaptation to anoxic environments

Membrane biophysical properties are critical to cell fitness and depend on unsaturated phospholipid acyl tails. These can only be produced in aerobic environments since eukaryotic desaturases require molecular oxygen. This raises the question of how cells maintain bilayer properties in anoxic environments. Here, we demonstrate the existence of an alternative pathway to regulate membrane fluidity that exploits phospholipid acyl-tail length asymmetry, replacing unsaturated species in the membrane lipidome. We show that the fission yeast, S. japonicus, which can grow in aerobic and anaerobic conditions, is capable of utilizing this strategy whereas its sister species, the well-known model organism S. pombe, cannot. The incorporation of asymmetric-tailed phospholipids might be a general adaptation to hypoxic environmental niches. One-Sentence SummaryIn anoxic environments, saturated asymmetric acyl-tailed phospholipids can replace unsaturated ones to maintain membrane physical properties.

cell biology↗

bioRxiv2022

Topology-based fluorescence image analysis for automated cell identification and segmentation

Cell segmentation refers to the body of techniques used to identify cells in images and extract biologically relevant information from them; however, manual segmentation is laborious and subjective. We present Topological Boundary Line Estimation using Recurrence Of Neighbouring Emissions (TOBLERONE), a topological image analysis tool which identifies persistent homological image features as opposed to the geometric analysis commonly employed. We demonstrate that topological data analysis can provide accurate segmentation of arbitrarily-shaped cells, offering a means for automatic and objective data extraction. One cellular feature of particular interest in biology is the plasma membrane, which has been shown to present varying degrees of lipid packing, or membrane order, depending on the function and morphology of the cell type. With the use of environmentally-sensitive dyes, images derived from confocal microscopy can be used to quantify the degree of membrane order. We demonstrate that TOBLERONE is capable of automating this task.

bioinformatics↗