Biology subjects

Rossello, F.

Publications and source records attributed to Rossello, F..

9 recordsLinked to original sources

bioRxiv2026

Attenuated interferon signalling in alveolar epithelium limits resistance to Streptococcus pyogenes

The upper respiratory tract is a primary niche for Streptococcus pyogenes colonisation and disease. Lower respiratory tract infection (pneumonia) is the most common invasive S. pyogenes syndrome. Studies have not previously examined how epithelial cells, from the airway to the alveolus, respond to S. pyogenes infection. Here, we established a scalable human in vitro model by differentiating induced pluripotent stem cells (iPSCs) into mature pseudostratified airway epithelium or alveolar type 2 epithelial cells, cultured at air-liquid interface and infected with S. pyogenes (M1UK and M75 strains). Both strains attached to iPSC-derived lung epithelial cells, with significantly greater adherence to the airway epithelium by M75 compared to M1UK. Moreover, invasion by both S. pyogenes strains of alveolar epithelial cells was greater than for the airway epithelium. Dynamic S. pyogenes gene expression changes were evident between 6 and 24 hours after infection, which was influenced by the infected cell type; however, virulence genes were not significantly altered. While infection of the airway epithelium induced rapid and dynamic inflammatory signalling, the alveolar epithelium demonstrated augmented cell death and mounted a transcriptional pro-inflammatory and proliferative response that was uncoupled from cytokine secretion. The airway epithelium model exhibited consistently higher baseline type I interferon (IFN) signalling than the alveolar epithelium. Invasion by S. pyogenes and inflammation was significantly reduced in IFN-{beta}-treated alveolar epithelial cells. In summary, we have established the first model of S. pyogenes infection in physiologically relevant airway and alveolar epithelial cells. Our findings suggest that host responses to infection are influenced by lung compartment, the S. pyogenes strain type, and infection timepoint, highlighting context-specific pathways that could be leveraged therapeutically.

microbiology↗

bioRxiv2025

Application of spatial transcriptomics across organoids: a high-resolution spatial whole-transcriptome benchmarking dataset

Stem cell-derived organoids hold promise to model tissue-specific disease. To enable this, it is crucial to assess how transcriptional signatures, cellular organisation and composition of organoids compare to in vivo counterparts. However, technologies which elucidate regional molecular identity, like spatial transcriptomics, have been challenging to apply to organoids. This study presents the first systematic profiling of multiple stem cell derived organoid models (brain, heart muscle, heart valve, kidney, lung, cartilage, and haematopoietic) with Stereo-seq, a full transcriptome, spatial transcriptomics assay using on-chip in situ RNA capture at subcellular resolution. It describes optimisation of this assay to characterise organoids, use of multiple organoid samples on a single chip, assess differences in RNA capture efficiency compared to reference tissues and its limitations. This study introduces a bespoke analysis method that partitions samples into regions and further characterises them. These findings inform future works to characterise organoids using spatial transcriptomics, providing insights in optimising RNA capture of multiple organoids across a chip and novel methods for regional analysis.

bioinformatics↗

bioRxiv2023

An interchange property for the rooted Phylogenetic Subnet Diversity on phylogenetic networks

Faiths Phylogenetic Diversity (PD) on rooted phylogenetic trees satisfies the so-called strong exchange property that guarantees that, for every two sets of leaves of different cardinalities, a leaf can always be moved from the largest set to the smallest in such a way that the sum of the PD values does not decrease. This strong exchange property entails a simple polynomial-time greedy solution to the PD optimization problem on rooted phylogenetic trees. In this paper we obtain an exchange property for the rooted Phylogenetic Subnet Diversity (rPSD) on rooted phylogenetic networks of bounded level and reticulations in-degree, which involves a more complicated interchange of leaves. We derive from it a polynomial-time greedy solution to the rPSD optimization problem on rooted semibinary level-2 phylogenetic networks.

bioinformatics↗

bioRxiv2020

Epigenetic reprogramming of plasmacytoid dendritic cells drives type I interferon-dependent differentiation of acute myeloid leukemias for therapeutic benefit

Pharmacological inhibition of epigenetic enzymes can have therapeutic benefit, particularly against hematological malignancies. While these agents can affect tumor cell growth and proliferation, recent studies have demonstrated that pharmacological de-regulation of epigenetic modifiers may additionally mediate anti-tumor immune responses. Here we discovered a novel mechanism of immune regulation through the inhibition of histone deacetylases (HDACs). In a genetically engineered model of t(8;21) AML, leukemia cell differentiation and therapeutic benefit mediated by the HDAC inhibitor panobinostat required activation of the type I interferon (IFN) signaling pathway. Plasmacytoid dendritic cells (pDCs) were identified as the cells producing type I IFN in response to panobinostat, through transcriptional activation of IFN genes concomitant with increased H3K27 acetylation at these loci. Depletion of pDCs abrogated panobinostat-mediated activation of type I IFN signaling in leukemia cells and impaired therapeutic efficacy, while combined treatment of panobinostat and recombinant IFN improved therapeutic outcomes. These discoveries offer a new therapeutic approach for t(8;21) AML and demonstrate that epigenetic rewiring of pDCs enhances anti-tumor immunity, opening the possibility of exploiting this cell type as a new target for immunotherapy.

cancer biology↗

bioRxiv2019

3D-Cardiomics: A spatial transcriptional atlas of the mammalian heart

Understanding spatial gene expression and regulation is key to uncovering developmental and physiological processes, during homeostasis and disease. Numerous techniques exist to gain gene expression and regulation information, but very few utilise intuitive true-to-life three-dimensional representations to analyze and visualize results. Here we combined spatial transcriptomics with 3D modelling to represent and interrogate, transcriptome-wide, three-dimensional gene expression and location in the mouse adult heart. Our study has unveiled specific subsets of genes that display complex spatial expression in organ sub-compartments. Also, we created a web-based user interface for spatial transcriptome analysis and visualization. The application may be accessed from http://3d-cardiomics.erc.monash.edu/.

systems biology↗

bioRxiv2019

AligNet: Alignment of Protein-Protein Interaction Networks

One of the most difficult problems difficult problem in systems biology is to discover protein-protein interactions as well as their associated functions. The analysis and alignment of protein-protein interaction networks (PPIN), which are the standard model to describe protein-protein interactions, has become a key ingredient to obtain functional orthologs as well as evolutionary conserved pathways and protein complexes. Several methods have been proposed to solve the PPIN alignment problem, aimed to match conserved subnetworks or functionally related proteins. However, the right balance between considering network topology and biological information is one of the most difficult and key points in any PPIN alignment algorithm which, unfortunately, remains unsolved. Therefore, in this work, we propose AligNet, a new method and software tool for the pairwise global alignment of PPIN that produces biologically meaningful alignments and more efficient computations than state-of-the-art methods and tools, by achieving a good balance between structural matching and protein function conservation as well as reasonable running times.

systems biology↗

bioRxiv2018

Sound Colless-like balance indices for multifurcating trees

The colless index is one of the most popular and natural balance indices for bifurcating phylogenetic trees, but it makes no sense for multifurcating trees. in this paper we propose a family of colless-like balance indices [C]D,f, which depend on a dissimilarity D and a function f: [N][->] [R] [>=]0, that generalize the colless index to multifurcating phylogenetic trees. We provide two functions f such that the most balanced phylogenetic trees according to the corresponding indices [C]D,f are exactly the fully symmetric ones. Next, for each one of these two functions f and for three popular dissimilarities D (the variance, the standard deviation, and the mean deviation from the median), we determine the range of values of [C]D,f on the sets of phylogenetic trees with a given number n of leaves. We end the paper by assessing the performance of one of these indices on TreeBASE and using it to show that the trees in this database do not seem to follow either the uniform model for multifurcating trees or the -{gamma}-model, for any values of and{gamma} .

evolutionary biology↗

bioRxiv2018

The Fair Proportion is a Shapley Value on phylogenetic networks too

The Fair Proportion of a species in a phylogenetic tree is a very simple measure that has been used to assess its value relative to the overall phylogenetic diversity represented by the tree. It has recently been proved by Fuchs and Jin to be equal to the Shapley Value of the coallitional game that sends each subset of species to its rooted Phylogenetic Diversity in the tree. We prove in this paper that this result extends to the natural translations of the Fair Proportion and the rooted Phylogenetic Diversity to rooted phylogenetic networks. We also generalize to rooted phylogenetic networks the expression for the Shapley Value of the unrooted Phylogenetic Diversity game on a phylogenetic tree established by Haake, Kashiwada and Su.

evolutionary biology↗

bioRxiv2018

A balance index for phylogenetic trees based on quartets

We define a new balance index for phylogenetic trees based on the symmetry of the evolutive history of every quartet of leaves. This index makes sense for polytomic trees and it can be computed in time linear in the number of leaves. We compute its maximum and minimum values for arbitrary and bifurcating trees, and we provide exact formulas for its expected value and variance for bifurcating trees under Fords -model and Aldous {beta}-model and for arbitrary trees under the -{gamma}-model.

evolutionary biology↗