Biology subjects

O'Sullivan, M.

Publications and source records attributed to O'Sullivan, M..

5 recordsLinked to original sources

bioRxiv2026

Distinct functions of Nup93 paralogs in tumor growth and Polycomb-mediated repression of JAK/STAT signaling

Nuclear pore complexes (NPCs) are nuclear envelope (NE)-embedded protein assemblies that mediate nucleocytoplasmic exchange and interact with the genome, including binding of an NPC component Nup93 to Polycomb chromatin domains. Here, we investigated the in vivo relevance of this relationship in Drosophila, which unusually contains two distinct paralogs of Nup93. Interestingly, we identified a Nup93-2-specific tumorigenic phenotype in larval wings, where depletion of Nup93-2, but not Nup93-1, led to tumor-like overgrowth, reminiscent of Polycomb mutations. Consistently, our transcriptomic analysis revealed a wide-spread loss of gene silencing in Nup93-2-depleted wings, particularly in a Nup93-bound Polycomb domain spanning genes for activators of JAK/STAT signaling. Nup93 paralogs were not found to differ in their effect on NPC biogenesis but strikingly, showed differences in subnuclear localization patterns. While Nup93-1 co-localized exclusively with fully assembled NPCs, Nup93-2 exhibited only partial co-localization and was found at additional NE locations in a tissue-specific manner. Together, our results identify an in vivo silencing role of a Nup93 paralog and suggest that Nup93-2 may form a unique NE-associated complex that targets a subset of Polycomb domains containing growth-promoting genes.

developmental biology↗

bioRxiv2025

Diagnosing linearity along the carbon cascade in terrestrial biosphere models

Elevated carbon dioxide (eCO2) fertilises photosynthesis, driving an increase in terrestrial gross primary production (GPP). However, it is unclear how effectively increased GPP propagates along the "carbon (C) cascade" to increase net primary production (NPP) and vegetation C stocks (Cveg) in different plant compartments. Vegetation models simulate divergent C cycle projections and have been criticised for being overly photosynthesis-driven (source-driven), neglecting processes that lead to non-linear behaviour in response to the GPP increase, which may attenuate (or amplify) changes in NPP and vegetation C stocks. Here, we introduce an analytical framework to diagnose linearity (L) of the land C cycle as the ratio of relative changes in linked fluxes and pools and apply it to outputs from 16 models of the TRENDY v11 ensemble. We found widely varying patterns in L across models and for the different links. Six models showed a clear dominance of larger relative changes in NPP than in GPP in global simulations (LNPP:GPP >1 for >60% of gridcells), indicating increased carbon use efficiency under eCO2. Only three models had LNPP:GPP < 1 for >60% of gridcells. Four models showed a clear dominance of larger relative changes in steady-state Cveg than in NPP, while five models showed an opposite pattern - in both cases with a large spread of LCveg*:NPP across gridcells within models. Three models showed a larger relative increase in root C than in Cveg, while two models showed a clear dominance of the opposite pattern. Widely differing distributions of L across models and links reveal a strong influence of alternative process representations (nonlinear behaviour) in individual models. However, for all links, L deviations from 1 were roughly balanced across the model ensemble, leading to an overall linear behaviour of terrestrial C cycle representations.

ecology↗

bioRxiv2025

A large global soil carbon sink informed by repeated soil samplings

Partitioning the terrestrial carbon sink between vegetation and soil is crucial for predicting future climate change, but the role of soils remains poorly quantified. Here, we compiled 3,099 soil organic carbon time series spanning five decades. We found a global soil organic carbon sink of 1.83 {+/-} 0.9 (mean {+/-} SE) petagrams per year from 1992 to 2020, driven by extratropical young forests, boreal old forests, and grasslands, while trends in tropical ecosystems remain uncertain. Our findings suggest the net land sink resides almost exclusively belowground as soil carbon, emphasizing the global opportunity of soil conservation and restoration for climate mitigation.

ecology↗

bioRxiv2022

STAT3 gain-of-function mutations connect leukemia with autoimmune disease by pathological dysregulation of NKG2Dhi CD8 killer T cells

The association between cancer and autoimmune disease is unexplained, exemplified by T-cell large granular lymphocytic leukemia (T-LGL) where gain-of-function somatic mutations in STAT3 correlate with co-existing autoimmunity. To resolve whether these mutations are the cause or consequence of CD8 clonal expansions and autoimmunity, here we analyse patients with germline STAT3 GOF syndrome and mice with the T-LGL mutation STAT3K658Nor the most common germline mutation, STAT3T716M. STAT3 GOF mutations drove accumulation of effector CD8 T cell clones highly expressing the NKG2D receptor for MHC-I-related molecules expressed on stressed cells, and the genes for inflammatory/cytotoxic granzymes, perforin, interferon-{gamma} and Ccl5/Rantes. CD8 cells were essential to lethal disease in Stat3K658Nmice and their accumulation required NKG2D and the receptor for IL-15 and IL-2, IL2RB. These results demonstrate that STAT3 GOF mutations cause effector CD8 T cell oligoclonal accumulation and that these rogue T cells contribute to autoimmune pathology, supporting the hypothesis that somatic mutations in leukemia/lymphoma driver genes contribute to autoimmune disease. IN BRIEFLeukemia and autoimmune-associated STAT3 gain-of-function mutations dysregulate CD8 T cells to cause autoimmune pathology and oligoclonal expansion of cytotoxic killer CD8 T cells, that depend upon NKG2D and IL2RB receptors for signals displayed on stressed, damaged, infected, or mutated tissues.

immunology↗

bioRxiv2021

Improved neutralization of the SARS-CoV-2 Omicron variant after Pfizer-BioNTech BNT162b2 COVID-19 vaccine boosting

In late November 2021, the World Health Organization declared the SARS-CoV-2 lineage B.1.1.529 the fifth variant of concern, Omicron. This variant has acquired 15 mutations in the receptor binding domain of the spike protein, raising concerns that Omicron could evade naturally acquired and vaccine-derived immunity. We utilized an authentic virus, multicycle neutralisation assay to demonstrate that sera collected one, three and six months post-two doses of Pfizer-BioNTech BNT162b2 has a limited ability to neutralise SARS-CoV-2. However, four weeks after a third dose, neutralising antibody titres are boosted. Despite this increase, neutralising antibody titres are reduced four-fold for Omicron compared to lineage A.2.2 SARS-CoV-2.

microbiology↗