Biology subjects

Bellini, E.

Publications and source records attributed to Bellini, E..

6 recordsLinked to original sources

bioRxiv2026

Unlocking Targeted Underwater Delivery of Coral Probiotics

The rapid global decline of coral reefs has intensified the need for innovative conservation strategies, including microbial therapies to enhance coral health and resilience. A major limitation, however, is the lack of effective delivery systems for administering Beneficial Microorganisms for Corals (BMCs). In this study, we present natural, biodegradable systems for the underwater delivery of probiotic bacteria to corals. Three customized alginate-based delivery formats (beads, hydrogels, and filaments) were developed and loaded with the probiotic Pseudoalteromonas peptidolytica. The materials were loaded with the bacterium at an average concentration of 10^(4) CFU/g of dry polymer and engineered to sink underwater while keeping their structural integrity over time. In vitro assays showed controlled release kinetics, with encapsulated probiotics remaining viable and capable of replication. In vivo experiments compared syringe-based inoculation with the application of alginate beads, hydrogels, and filaments to corals. Microbiome analyses performed before and after inoculation confirmed successful probiotic colonization following deployment of the alginate-based delivery systems. Relative abundance of the probiotic genus Pseudoalteromonas increased markedly in treated corals, reaching 11.5 % after 48 h with alginate beads, 12.7 % after 48 h with hydrogels, and 12.6 % after 24 h with filaments. Furthermore, the degradation mechanisms of the three delivery systems were investigated. As the first biomaterial-based underwater delivery systems specifically engineered for coral probiotics, these alginate-based materials provide a promising foundation for advancing microbial therapies in both controlled aquaria and natural reef environments.

bioengineering↗

bioRxiv2026

Suppression of YAP/TAZ molecular targets by epigenetic editing interferes with GBM growth and invasiveness

Glioblastoma (GBM) is a highly aggressive brain tumor characterized by extensive heterogeneity, diffuse invasion, and recurrence despite multimodal therapy. Aberrant transcriptional programs driven by oncogenic signaling pathways sustain GBM growth, stemness, and therapy resistance, yet targeting individual molecular nodes has yielded limited clinical benefit. Here, we introduce a transcriptional rewiring strategy based on an engineered epigenetic silencer factor (ESF) targeting the YAP/TAZ-TEAD axis. We developed a TEAD1 Epigenetic Silencer (TES) by fusing the DNA-binding domain of TEAD1 to repressive epigenetic modules. TES selectively binds TEAD genomic targets and imposes stable transcriptional repression of YAP/TAZ-dependent gene programs through chromatin remodeling and DNA methylation. Genome-wide analyses revealed that TES preserves TEAD1 DNA-binding specificity while converting an oncogenic transcriptional platform into a repressive state. Functionally, TES impaired proliferation, induced cell death, and reduced migratory and invasive properties in glioma cell lines and patient-derived cancer stem-like cells. In vivo, TES significantly reduced tumor growth in orthotopic GBM xenograft models and enhanced the therapeutic efficacy of temozolomide. Importantly, TES was well tolerated by normal neural cells in vitro and in the adult mouse brain in vivo. These findings establish TES as a proof-of-concept epigenetic therapy to durably suppress oncogenic transcriptional networks in GBM.

cancer biology↗

bioRxiv2023

Anti-tumor Efficacy of in situ Vaccination Using Bacterial Outer Membrane Vesicles

In situ vaccination (ISV) is a promising cancer immunotherapy strategy, consists in the intratumoral administration of immunostimulatory molecules (adjuvants). The rationale is that tumor antigens are abundant at the tumor site and therefore to elicit an effective anti-tumor immune response all is needed is an adjuvant, which can turn the immunosuppressive environment into an immunologically active one. Bacterial Outer Membrane Vesicles (OMVs) are potent adjuvants since they contain a number of microbe-associated molecular patterns (MAMPs) naturally present in the outer membrane and in the periplasmic space of Gram-negative bacteria. Therefore, they appear particularly indicted for ISV. In this work we first show that the OMVs from E. coli BL21(DE3){Delta}60 strain promote a strong anti-tumor activity when intratumorally injected into the tumors of two different mouse models. Tumor inhibition correlates with a rapid infiltration of DCs and NK cells. We also show that the addition of neo-epitopes to OMVs synergizes with the vesicle adjuvanticity, as judged by a two-tumor mouse models. Overall, our data support the use of the OMVs in ISV and suggests that ISV efficacy could benefit from the addition of properly selected tumor-specific neo-antigens.

cancer biology↗

bioRxiv2022

Balanced SET levels favor the correct enhancer repertoire during cell fate acquisition

Within the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering with the net charges of the nucleosomes, is a key player in this regulation. Here, we report that the onco-protein SET is a critical determinant for the levels of histone acetylation within enhancers. We disclose that conditions in which SET is accumulated, including the severe Schinzel-Giedion Syndrome (SGS), are characterized by a failure in the usage of the distal regulatory regions typically employed during fate commitment. This is accompanied by the usage of alternative enhancers leading to a massive rewiring of the distal control of the gene transcription. This represents a (mal)adaptive mechanism that, on one side, allows to achieve a certain degree of differentiation, while on the other affects the fine and corrected maturation of the cells. Thus, we propose the differential in cis-regulation as a contributing factor to the pathological basis of the SET-related disorders in humans, including SGS, neurodevelopmental disorders, myeloproliferative diseases, and cancer.

developmental biology↗

bioRxiv2022

MCT1-dependent energetic failure and neuroinflammation underlie optic nerve degeneration in Wolfram syndrome mice

Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in the WFS1 gene leading to a wide spectrum of clinical dysfunctions, among which blindness, diabetes and neurological deficits are the most prominent. WFS1 encodes for the endoplasmic reticulum (ER) resident transmembrane protein Wolframin with multiple functions in ER processes. However, the WFS1-dependent etiopathology in retinal cells is unknown. Herein, we showed that Wfs1 mutant mice developed early retinal electrophysiological impairments followed by marked visual loss. Interestingly, axons and myelin disruption in the optic nerve preceded the degeneration of the retinal ganglion cell bodies in the retina. Transcriptomics at pre-degenerative stage revealed the STAT3-dependent activation of proinflammatory glial markers with reduction of the homeostatic and pro-survival factors Glutamine synthetase and BDNF. Furthermore, label-free comparative proteomics identified a significant reduction of the monocarboxylate transport isoform 1 (MCT1) and its partner Basigin that are highly enriched on retinal astrocytes and myelin-forming oligodendrocytes in optic nerve together with Wolframin. Loss of MCT1 caused a failure in lactate transfer from glial to neuronal cell bodies and axons leading to a chronic hypometabolic state. Thus, this bioenergetic impairment is occurring concurrently both in the axonal regions and cell bodies of the retinal ganglion cells, selectively endangering their survival while impacting less on other retinal cells. This metabolic dysfunction occurs months before the frank RGC degeneration suggesting an extended time window for intervening with new therapeutic strategies focused on boosting retinal and optic nerve bioenergetics in WS1.

neuroscience↗

bioRxiv2021

Outer Membrane Vesicles from the gut microbiome contribute to tumor immunity by eliciting cross-reactive T cells

The gut microbiome plays a key role in cancer immunity. One proposed mechanism is through the elicitation of T cells, which incidentally recognize neo-epitopes arising from cancer mutations ("molecular mimicry (MM)" hypothesis). To support MM, Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA) and orally administered to C57BL/6 mice. The treatment elicited OVA-specific CD8+ T cells in the lamina propria and inhibited the growth of OVA-B16F10 tumors. Importantly, the administration of Outer Membrane Vesicles (OMVs) engineered with different T cell epitopes elicited epitope-specific T cells and inhibited tumor growth. Microbiome shotgun sequencing and TCR sequencing provided evidence that cross-reacting T cells were induced at the mucosal level and subsequently reached the tumor site. Overall, our data support the role of MM in tumor immunity, assign a new role to OMVs and pave the way to new probiotics/OMV-based anti-cancer immunotherapies.

microbiology↗