Biology subjects

Oliver, L.

Publications and source records attributed to Oliver, L..

5 recordsLinked to original sources

bioRxiv2026

Hawaiian Geothermal Fumaroles Contain Diverse and Novel Viruses

Microbial communities of geothermal habitats are central to understanding the evolution of life on Earth. Metagenomics has provided insight into the role of viruses in shaping microbial diversity of complex environments. However, identification of novel viruses is constrained by lack of marker genes and low nucleotide similarities between related viral taxa. While microbial and viral diversity have been explored in terrestrial hot springs and hydrothermal vent systems, other volcanic features remain underexplored. Fumaroles (steam vents) are geothermal features that heat groundwater with magma, releasing steam and volcanic gases such as CO2 and H2S. Comparatively physicochemically dynamic to hot springs, fumarole temperatures and gas emissions rapidly fluctuate with volcanic activity. Here, we describe viruses identified metagenomically from microbial mats hosted near basaltic fumaroles on the Big Island of Hawaii. To our knowledge, this is the first systematic survey of fumarole viruses. Our utilization of a sensitive profile-based approach for identification reveals high viral diversity in fumaroles, resulting in estimation of two undescribed order-level clades of Caudoviricetes (tailed phages). Viral metabolic genes provide evidence of viral-mediated adaptation of microbes to fumarole conditions. We describe patterns of viral diversity that diverge from the Bank model of viral ecology, hinting at viral dispersal between biofilms and high viral richness and evenness. Lastly, we provide a description of the first terrestrial geothermal environment dominated by Microviridae, previously only described in viral communities of deep ocean hydrothermal vents. This study offers important findings for exploration of viral ecology in extreme environments.

microbiology↗

bioRxiv2025

Brassinosteroids mediate proper coordination of sepal elongation

Arabidopsis sepals must grow in a coordinated and robust fashion to a consistent size and shape to close and protect the developing flower bud. To understand how this robust coordination occurs, we use the loss of robustness mutant development related myb-like1 (drmy1), which exhibits variable sepal initiation and growth, causing failure of the sepals to close the flower bud. Specifically, drmy1 has overgrown outer (abaxial) sepals and undergrown inner (adaxial) sepals, leading to a large discrepancy in the sizes of different sepals within individual flower buds. Using single cell and spatial RNA-seq, we found changes in expression of key genes related to brassinosteroid (BR) signaling in drmy1, particularly in cell types important to young flower bud development such as epidermal cells, boundary cells, and meristematic cells. Confocal imaging of a BRI1-EMS-SUPPRESSOR1 (BES1) ratiometric reporter confirms that BR signaling is upregulated and more variable in young drmy1 sepals. Subsequently, we found that altering BR signaling in drmy1 by crossing with BR mutants or adding brassinolide (a potent brassinosteroid) or brassinazole (a brassinosteroid biosynthesis inhibitor) can partially rescue this elongation defect by differentially altering the relative growth of the inner and outer sepals. Increasing BR signaling rescues by increasing the growth of the inner sepal but not the outer sepal, while decreasing BR signaling rescues by decreasing the growth of the outer sepal but not the inner sepal. These results suggest that brassinosteroids mediate the robust coordination of the growth rates between inner and outer sepals during early development, ensuring proper flower bud closure.

developmental biology↗

bioRxiv2024

PARP inhibitor counteracts Temozolomide Resistance in Glioblastoma Multiforme

BackgroundGlioblastoma multiforme (GBM) is the most common malignant primary brain tumour in adults and is invariably associated with poor prognosis. Resistance to Temozolomide (TMZ), the standard chemotherapeutic agent, remains a major clinical challenge, particularly due to DNA mismatch repair (MMR) deficiencies. The aim of this study was to determine whether combining TMZ with the poly(ADP-ribose) polymerase inhibitor Olaparib (OLA) could overcome TMZ resistance in GBM. MethodsWe conducted in vitro experiments using U251 cell-line, including a TMZ-resistant derivative, and primary GBM cultures derived from patient tumours. A CRISPR/Cas9 knockout screen was employed to identify genes involved in TMZ resistance. Cell viability, proliferation, and morphology were assessed following treatment with TMZ, OLA, or their combination. ResultsThe CRISPR screen identified inactivation of MMR pathway genes as key mediators of TMZ resistance. Co-treatment with OLA and TMZ demonstrated synergistic cytotoxicity in both parental and TMZ-resistant U251 cells, as well as in primary GBM cultures at diagnosis or relapse. Notably, OLA restored sensitivity to TMZ in MMR-deficient contexts and in tumours expressing O6-methylguanine-DNA-methyltransferase (MGMT). The combination treatment induced persistent DNA damage, cell cycle disruption, and cell death. ConclusionsThese findings provide strong preclinical evidence that combining TMZ with OLA can effectively overcome key mechanisms of TMZ resistance in GBM. This approach offers a promising therapeutic strategy warranting further clinical investigation. IMPORTANCE OF THE STUDYTemozolomide (TMZ) resistance remains a major therapeutic obstacle in glioblastoma (GBM), often driven by MMR deficiency or MGMT expression. While poly(ADP-ribose) polymerase (PARP) inhibitors have shown potential in other cancers, their role in overcoming TMZ resistance in GBM has remained unclear. In this study, a CRISPR screen identified MMR deficiency as a key driver of TMZ resistance. We further demonstrate that co-treatment with the PARP inhibitor Olaparib (OLA) restores TMZ sensitivity in both MMR-deficient and MGMT-expressing GBM cells and patient-derived cultures. These findings provide strong preclinical evidence supporting PARP inhibition as a promising therapeutic strategy to overcome chemoresistance in GBM and justify further clinical investigation. KEY POINTSO_LIPARP inhibitor Olaparib restores temozolomide sensitivity in resistant GBM cells C_LIO_LICombination therapy overcomes resistance driven by MMR deficiency or MGMT expression C_LIO_LIDual treatment induces persistent DNA damage and apoptosis in glioblastoma primary cultures C_LI

cancer biology↗

bioRxiv2022

Pyruvate carboxylation identifies Glioblastoma Stem-like Cells opening new metabolic strategy to prevent tumor recurrence

Glioblastoma (GBM) are currently associated with a dismal prognosis due to therapeutic resistance. Within the diverse tumor subpopulations, Glioblastoma Stem-like Cells (GSC) have been involved in GBM recurrence. In our study, we demonstrated that these tumor cells can be identified through singular mitochondrial alternative metabolisms. Combining state-of-the-art metabolic studies and the development of a straightforward tumoroid model recapitulating key features of primary GBM cultures, we uncovered a significant use of -ketoglutarate reductive carboxylation and pyruvate carboxylation in tumoroid GBM cells, catalyzed respectively by isocitrate dehydrogenase and pyruvate carboxylase enzymes. We demonstrated that these singular metabolic features are shared by GBM cells from the mesenchymal subtype and radiation-escaping cells, also involved in recurrence. Finally, we demonstrated that pyruvate carboxylation is required for GBM cell survival in hypoxic niches where glutamine is restricted. Thus, besides providing a new way to identify GSC, our study also opens new therapeutic strategy to limit GBM recurrence.

cancer biology↗

bioRxiv2021

Mechanistic insights of radiation-induced endothelial senescence impelling glioblastoma genomic instability at relapse

Despite aggressive clinical protocol, all glioblastoma (GBM) recur at the initial site within the irradiated peritumoral microenvironment. Whereas irradiated microenvironment has been recently proposed to accelerate GBM relapse, molecular and cellular mechanisms remain unknown. Here, using relevant in vitro and in vivo models, we decipher how radiation-induced endothelial senescence drives the emergence of aggressive GBM cells. Secretome (SASP) of radiation-induced senescent (RIS) endothelium enhances genomic instability and intratumoral heterogeneity in irradiated GBM cells. In-depth molecular studies revealed that CXCL5 and CXCL8, from the SASP, activate CXCR2 receptor on tumor cells leading to increased DNA hyper-replication, micronuclei formation and aneuploidy. Importantly, through CXCL5/8-CXCR2 axis activation, this SASP increases GBM aggressiveness in vivo. Both chemokines were detected in relapsing, but not primary, GBM biopsies and positively correlated with worst patient outcome. In conclusion, we identify new molecular and preclinical insights of relapsing GBM aggressiveness where RIS vascular niches fuel aggressive tumor emergence.

cancer biology↗