Biology subjects

Niemeyer, F.

Publications and source records attributed to Niemeyer, F..

3 recordsLinked to original sources

bioRxiv2026

Spatial transcriptomics reveals interferon pathway enrichment in early relapsing serous carcinoma

High-grade serous carcinoma (HGSC) is characterized by extensive inter and intra-patient heterogeneity, complicating the identification of reliable prognostic biomarkers and the prediction of treatment response. In clinical practice, the origin of diagnostic biopsies varies, from tubo-ovarian (adnexal) tissue to omental or peritoneal metastatic foci. Whether the different sites provide similar information for molecular characterization or treatment decisions remains unclear. Studies comparing site-specific molecular details and the spatial relationship of HGSC tissue from patients with different treatment outcomes could provide answers to the open questions. Here, we used spatial transcriptomics to profile matched treatment-naive adnexal and omental tumor samples from nine HGSC patients stratified by platinum-free interval (PFI). Pathway enrichment analysis revealed several differences between short and medium- and long PFI tumors, however most of these differences were site-agnostic. Most strikingly, tumor epithelium from short PFI patients showed an inflammatory phenotype driven by increased interferon response signaling, carried by effector interferon-stimulated gene expression at both tumor sites. Further, medium- and long PFI tumors were enriched for proliferative and cell cycle regulatory programs. Differential gene expression and copy-number analyses identified three genes, complement gene C3, and interferon-related genes IFI27 and BST2, consistently associated with short PFI across adnexal and omental sites. These were validated at the tissue level using RNA in-situ hybridization. A case study of copy-number-defined subclones further suggested that this phenotype can arise as a distinct subclonal population within a single tumor. Outcome analysis, using two publicly available ovarian cancer cohorts, showed that high C3 expression was significantly associated with shorter platinum-free survival. Together, these findings implicate complement and interferon signaling as concurrent features of treatment-naive HGSC tumors with early relapse in both adnexal and omental tissue, and nominate C3 as a candidate prognostic biomarker and potential therapeutic target.

cancer biology↗

bioRxiv2024

The archaeal family 3 polyphosphate kinase reveals a function of polyphosphate as energy buffer under low energy charge

Inorganic polyphosphate, a linear polymer of orthophosphate residues linked by phosphoanhydride bonds, occurs in all three domains of life and plays a diverse and prominent role in metabolism and cellular regulation. While the polyphosphate metabolism and its physiological significance have been well studied in bacteria and eukaryotes including human, there are only few studies in archaea available so far. In Crenarchaeota including members of Sulfolobaceae, the presence of polyphosphate and degradation via exopolyphosphatase has been reported and there is some evidence for a functional role in metal ion chelation, biofilm formation, adhesion and motility, however, the nature of the crenarchaeal polyphosphate kinase is still unknown. Here we used the crenarchaeal model organism Sulfolobus acidocaldarius to study the enzymes involved in polyphosphate synthesis. The two genes annotated as thymidylate kinase (saci_2019 and saci_2020), localized downstream of the exopolyphosphatase, were identified as the missing polyphosphate kinase in S. acidocaldarius (SaPPK3). Thymidylate kinase activity was confirmed for Saci_0893. Notably Saci_2020 showed no polyphosphate kinase activity on its own but served as regulatory subunit (rPPK3) and was able to enhance polyphosphate kinase activity of the catalytically active subunit Saci_2019 (cPPK3). Heteromeric polyphosphate kinase activity is reversible and shows a clear preference for polyP-dependent nucleotide kinase activity, i.e. polyP-dependent formation of ATP from ADP (12.4 U/mg) and to a lower extent of GDP to GTP whereas AMP does not serve as substrate. PPK activity in the direction of ATP-dependent polyP synthesis is rather low (0.25 U/mg); GTP was not used as phosphoryl donor. A combined experimental modelling approach using quantitative 31P NMR allowed to follow the reversible enzyme reaction for both ATP and polyP synthesis. PolyP synthesis was only observed when the ATP/ADP ratio was kept high, using an ATP recycling system. In absence of such a recycling system, all incubations with polyP and PPK would reach an equilibrium state with an ATP/ADP ratio between 3 and 4, independent of the initial conditions. Structural and sequence comparisons as well as phylogenetic analysis reveal that the S. acidocaldarius PPK is a member of a new PPK family, named PPK3, within the thymidylate kinase family of the P-loop kinase superfamily, clearly separated from PPK2. Our studies show that polyP, in addition to its function as phosphate storage, has a special importance for the energy homeostasis of S. acidocaldarius and due to its reversibility serves as energy buffer under low energy charge enabling a quick response to changes in cellular demand.

microbiology↗

bioRxiv2023

Stromule geometry allows optimal spatial regulation of organelle interactions in the quasi-2D cytoplasm

In plant cells, plastids form elongated extensions called stromules, the regulation and purposes of which remain unclear. Here we quantitatively explore how different stromule structures serve to enhance the ability of a plastid to interact with other organelles: increasing the effective space for interaction and biomolecular exchange between organelles. Strikingly, electron microscopy and confocal imaging showed that the cytoplasm in Arabidopsis thaliana and Nicotiana benthamiana epidermal cells is extremely thin (around 100 nm in regions without organelles), meaning that inter-organelle interactions effectively take place in 2D. We combine these imaging modalities with mathematical modelling and new in planta experiments to demonstrate how different the elongation of stromules (single or multiple, linear or branching) could be employed to optimise different aspects of inter-organelle interaction capacity in this 2D space. Stromule formation and branching is shown to provide a proportionally higher benefit to interaction capacity in 2D than in 3D. Additionally we find this benefit depends on optimal plastid spacing. We hypothesize that cells can promote the formation of different stromule architectures in the quasi-2D cytoplasm to optimise their interaction interface to meet specific requirements. These results provide new insight into the mechanisms underlying the transition from low to high stromule numbers during biotic stress, the consequences for interaction with smaller organelles, how plastid access and plastid to nucleus signalling is balanced, as well as the impact of plastid density on organelle interaction.

plant biology↗