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Nadal, C.

Publications and source records attributed to Nadal, C..

3 recordsLinked to original sources

Condensation of the RNA chaperone Hfq is coupled to inhibition of carbon assimilation and contributes to the stabilisation of regulatory RNAs in nitrogen starved Escherichia coli

Ribonucleoprotein-condensates are membraneless compartments that concentrate RNA-binding proteins and RNA and play key roles in cellular adaptation across both eukaryotes and bacteria. While the biological roles of ribonucleoprotein-condensates are better understood in eukaryotic systems, the knowledge of metabolic processes that govern their formation and their contribution to stress adaptation remains at a nascent stage in bacterial RNA biology. Hfq is an RNA-chaperone conserved in many bacteria that undergoes condensation in response to diverse stresses. Using nitrogen (N) starvation in Escherichia coli as a model stress condition, we show that Hfq condensation occurs independently of any extracellular cues, cytoplasmic shrinkage that cells undergo during N starvation or the canonical NtrBC-dependent adaptive response to N starvation. However, we demonstrate that Hfq condensation is coupled to the inhibition of carbon assimilation in N-starved E. coli. Further, by comparing the transcriptomes of wild-type bacteria and bacteria unable to form Hfq-condensates, we reveal that Hfq-condensates contribute to the stabilisation of Hfq-associated non-coding regulatory RNAs. We propose that coordination of carbon and N metabolism during N starvation, critical for metabolic adaptation, is accompanied by preservation of non-coding regulatory RNAs via Hfq condensation.

microbiology↗

The mechanical anisotropy of adipose tissues regulates ovarian cancer invasion

High-grade serous ovarian cancer, the most common and aggressive form of ovarian cancer, generally metastasises to visceral adipose tissues. In these tissues, the extracellular matrix through which ovarian cancer cells adhere and migrate is confined by the presence and preponderance of adipocytes. How cells migrate in this unique environment is not known, yet critical to understanding metastatic progression. To study these processes, we develop biomimetic organo-hydrogels that recreate structural and mechanical properties of human visceral adipose tissues. We show that ovarian cancer cells present invasive tropism towards organo-hydrogels, replicating the behaviour observed in native adipose tissues. This migration is facilitated by the mechanical anisotropy and microstructure of organo-hydrogels and adipose tissues, allowing the formation of cell force-induced migratory tracks, a process regulated by TGF{beta} in an MMP degradation-independent manner. These results highlight the contribution of adipocytes to tissue biophysical features as a key regulatory factor of ovarian cancer cell migration.

bioengineering↗

Engineered Protein Nanosheets for the Scale up of Mesenchymal Stem Cell Culture on Bioemulsions

The rapid progress in cell therapies and stem cell technologies requires the development of novel bioprocessing and biomanufacturing pipelines able to cope with the scale up of cell manufacturing. In this respect, microdroplet technologies have already revolutionised the field of biotechnologies, but remain ill-suited to the culture of adherent cells. In this report, we describe the engineering of albumins with cell adhesive peptides for the stabilisation of microdroplets enabling the scale up of mesenchymal stem cell (MSC) expansion. We characterise the modified albumins prior to study their self-assembly at liquid-liquid interfaces via interfacial shear rheology, and mechanical strengthening through the formation of crosslinked nanosheets. The biofunctionalisation of these protein nanosheets is then characterised by fluorescence microscopy. In turn, the ability of the resulting bioactive microdroplets to promote rapid cell adhesion and expansion is examined and the extensive deposition of matrix associated with such cultures is characterised. The culture of MSCs is then scaled up 100 fold, first at the surface of fluorinated oil emulsions, then on plant-based emulsions stabilised by engineered protein nanosheets and the phenotype of resulting cells is characterised. The microdroplet culture system presented displays attractive advantages over existing technologies, in terms of simplicity of processing, compatibility with regulatory expectations and costs of production, and offers exciting opportunities for translation to cell manufacturing, for cell therapies and cultivated meat applications.

bioengineering↗