Biology subjects

Paci, G.

Publications and source records attributed to Paci, G..

3 recordsLinked to original sources

bioRxiv2025

3D epithelial cell topology tunes signalling range to promote precise patterning

Cell behaviours in multicellular organisms are coordinated via both diffusible molecules and by signals based on direct cell-cell contacts. The mode of cell communication used influences the signalling range. In many developing epithelia, contact-based Notch-Delta lateral inhibition signalling is used to pattern cell fates. While previous work revealed that cells can use protrusions to extend the range of Notch-Delta signalling to alter these patterns, this is not a general feature of epithelia. In addition, it is not known how the complex three-dimensional (3D) shapes of epithelial cells influence cell communication. In exploring this question, we show that epithelial cells at the Drosophila wing margin, which lack basal protrusions, contact different neighbours at different heights along their apico-basal axis, effectively increasing the number of neighbours each cell touches. To quantitatively assess this behaviour, we develop a novel mathematical modelling framework (Multi-layer Signalling Model) to simulate Notch-Delta signalling over data-derived 3D cell topologies. The model predicts that lateral cell surface signalling is essential to tune the spacing between SOPs. In agreement, we show that perturbing cortical stiffness and cell tortuosity in vivo modifies SOP spacing. These results emphasise the importance of 3D cell geometry and topology in fine-tuning signalling range.

developmental biology↗

bioRxiv2024

Assessing the potential of vision language models for automated phenotyping of Drosophila melanogaster

Model organisms such as Drosophila melanogaster are extremely well suited to performing large-scale screens, which often require the assessment of phenotypes in a target tissue (e.g., wing and eye). Currently, the annotation of defects is either performed manually, which hinders throughput and reproducibility, or based on dedicated image analysis pipelines, which are tailored to detect only specific defects. Here, we assess the potential of Vision Language Models (VLMs) to automatically detect aberrant phenotypes in a dataset of Drosophila wings and provide their descriptions. We compare the performance of one the current most advanced multimodal models (GPT-4) with an open-source alternative (LLaVA). Via a thorough quantitative evaluation, we identify strong performances in the identification of aberrant wing phenotypes when providing the VLMs with just a single reference image. GPT-4 showed the best performance in terms of generating textual descriptions, being able to correctly describe complex wing phenotypes. We also provide practical advice on potential prompting strategies and highlight current limitations of these tools, especially around misclassification and generation of false information, which should be carefully taken into consideration if these tools are used as part of an image analysis pipeline.

bioinformatics↗

bioRxiv2019

Molecular determinants of large cargo transport into the nucleus

Transport of molecules between the nucleus and the cytoplasm is tightly regulated by the nuclear pore complex (NPC). Even very large cargoes such as many pathogens, mRNAs and pre-ribosomal subunits can pass the NPC intact. Compared to small import complexes, for such large cargoes >15 nm there is very little quantitative understanding of the mechanism for efficient transport, the role of multivalent binding to nuclear transport receptors via nuclear localisation sequences (NLSs) and effects of size differences. Here, we assayed nuclear import kinetics in cells for a total of 30 large cargo models based on four capsid-like particles in the size range of 17-36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for transport scale non-linearly with size and obey a minimal cut off of functional import requiring more than 10 NLS in the lowest case. Together, our results reveal the key molecular determinants on large cargo import kinetics in cells.

biophysics↗