Biology subjects

Issa, R.

Publications and source records attributed to Issa, R..

3 recordsLinked to original sources

bioRxiv2023

Functioning human lung organoids model pulmonary tissue response from carbon nanomaterial exposures

Human lung organoids (HLOs) are increasingly used to model development and infectious diseases, however their ability to recapitulate functional pulmonary tissue response to nanomaterial (NM) exposures has yet to be demonstrated. Here, we established a lung organoid exposure model that utilises microinjection to present NMs into the lumen of organoids. Our model assures efficient, reproducible and controllable exposure of the apical pulmonary epithelium, emulating real-life human exposure scenario. By comparing the impact of two well studied carbon-based NMs, graphene oxide sheets (GO) and multi-walled carbon nanotubes (MWCNT), we validated lung organoids as tools for predicting pulmonary NM-driven responses. In agreement with established in vivo data, we demonstrate that MWCNT, but not GO, elicit adverse effects on lung organoids, leading to a pro-fibrotic phenotype. Our findings reveal the capacity and suitability of HLOs for hazard assessment of NMs, aligned with the much sought-out 3Rs (animal research replacement, reduction, refinement) framework.

pharmacology and toxicology↗

bioRxiv2023

CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway

ObjectivesEpithelial colonisation is a critical first step in bacterial pathogenesis. Staphylococcus aureus can utilise several host factors to associate with cells, including 5{beta}l integrin and heparan sulphate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process while integrins are only critical for post-adhesion entry into human epithelial cells. Methods and ResultsTreatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion whereas blockade of {beta}1 integrins did not affect adhesion but did reduce the subsequent internalisation of adhered bacteria. CD9 disruption or deletion increased {beta}1 integrin-mediated internalisation, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalisation. ConclusionsCD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organisation to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogues could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis.

microbiology↗

bioRxiv2019

A single microRNA system controls complex movement in morphologically distinct forms of Drosophila

Movement is the main output of the nervous system. It emerges during development to become a highly coordinated physiological process essential to the survival and adaptation of the organism to the environment. Similar movements can be observed in morphologically-distinct developmental stages of an organism, but it is currently unclear whether these movements have a common or diverse molecular basis. Here we explore this problem in Drosophila focusing on the roles played by the microRNA (miRNA) locus miR-iab4/8 which was previously shown to be essential for the fruit fly larva to correct its orientation if turned upside down (self-righting) (Picao-Osorio et al., 2015). Our study shows that miR-iab4 is required for normal self-righting across all three Drosophila larval stages. Unexpectedly, we also discover that this miRNA is essential for normal self-righting behaviour in the Drosophila adult, an organism with radically different morphological and neural constitution. Through the combination of gene-expression, optical imaging and quantitative behavioural approaches we provide evidence that miR-iab4 exerts its effects on adult self-righting behaviour through repression of the Hox gene Ultrabithorax (Ubx) (Morgan, 1923; Sanchez-Herrero et al., 1985) in a specific set of motor neurons that innervate the adult Drosophila leg. Our results show that this miRNA-Hox module affects the function, rather than the morphology of motor neurons and indicate that post-developmental changes in Hox gene expression can modulate behavioural outputs in the adult. Altogether our work reveals that a common miRNA-Hox genetic module can control complex movement in morphologically-distinct organisms and describes a novel post-developmental role of the Hox genes in adult neural function.

neuroscience↗