Biology subjects

Kolb, S.

Publications and source records attributed to Kolb, S..

5 recordsLinked to original sources

bioRxiv2026

The structural mechanism of eukaryotic fluoride channel activation and inhibition by monovalent cations

Fluoride is an environmentally prevalent inhibitor of fungi, plants, and other eukaryotes. The fluoride exporter (FEX) is the major resistance mechanism that prevents intracellular fluoride accumulation in eukaryotes. FEX activity is sodium-dependent, but the mechanism for Na+ activation and the impact of other cations on FEX function remain poorly understood. Here, we show that sodium and lithium have different effects on channel activity. We leverage these differences to understand how monovalent cations regulate FEX. Functional assays in a reconstituted system show that lithium acts as a competitive antagonist of channel activation by competing with sodium for the central cation binding site. We further demonstrate that FEX inhibition by lithium has consequences in vivo, as lithium markedly reduces fluoride tolerance of yeast. A cryo-EM structure of Candida albicans FEX with Li+, together with molecular dynamics (MD) simulations, reveals the structural mechanism underlying cation-dependent FEX activity. Whereas sodium binding supports a dynamic structure with a broader pore radius, lithium coordination causes a more rigid conformation that is more compact in the channels vestibule. These changes perturb the tilt angle of a pore lining helix, and the alter the rotamer of a key phenylalanine in the pore, which together constrict the permeation pathway. In addition to providing general insight into the mechanism of fluoride channel regulation by monovalent cations, these results identify lithium as a previously unknown environmental antagonist of eukaryotic fluoride export and tie cellular fluoride stress tolerance to the abundance of additional ions in the cellular milieu.

biochemistry↗

bioRxiv2026

SATB1 is a targetable modulator of JAK-STAT signaling and cytokines in human Treg and Tconv cells

The chromatin organizer SATB1 is indispensable for thymic regulatory T cell (Treg cell) development and T helper cell induction. Several gene loci have been described to be SATB1-controlled, including the transcription factor GATA3 and the cytokine loci IL-4 and IL-17. However, the global effects of SATB1 on fully differentiated human CD4 conventional T cells (Tconv cells) and Treg cells, and thus SATB1s potential as a target for T cell engineering, are poorly understood. We describe SATB1-regulated gene signatures as largely subset-specific, with broader effects on Treg cells. Despite of the distinct gene-regulatory patterns, we observe overarching dysregulated cytokine and JAK-STAT signaling after SATB1 ablation. Functionally, SATB1 KO reduces human Treg cell suppressive capacities but boosts tumor clearance via CD4 CAR T cells in a preclinical, humanized mouse model. Together, Treg destabilization and simultaneous increased activation of CD4 CAR T cells by SATB1 modulation may be an interesting strategy to boost the efficiency of CAR T cell therapies.

immunology↗

bioRxiv2025

Methane sink function of grassland soil microbiomes - negative effects of intensive management persist three years after land-use extensification

Grassland soils are important methane (CH4) sinks through CH4 oxidation by methanotrophs, but intensive management with high nitrogen inputs and grazing densities reduces this potential. While long-term recovery of the CH4 sink after land-use change is generally established, little is known about the short-term effects of reducing land-use intensity index (LUI) through extensive management in grassland. We did not find an effect on potential CH4 oxidation rates (PMORs) and the abundances atmospheric CH4-consuming methanotrophs after three years of LUI reduction (no fertilization, no grazing, and one mowing per year) in 45 intensively managed grassland sites located in three different pedoclimatic regions of Germany. However, we observed a decline in the abundance of CH4 producing methanogens. Moreover, we found greater PMORs and higher abundance of Upland Soil Cluster {gamma} (USC{gamma}) methanotrophs on additional, historically low LUI sites. Soil bulk density decreased already after three years of LUI reduction and was even lower in historically low LUI sites. Strong correlations between the abundance canonical methanotrophs and methanogens highlight a CH4 filter function that was independent from LUI reduction across regions. Our study consistently shows that three years of LUI reduction are not sufficient to restore the CH4 sink function of temperate grasslands. However, the lower soil bulk density and the decreased abundance of methanogens indicate that LUI reduction will affect the habitat and living boundary conditions for CH4-cycling microorganisms in the long term. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=133 SRC="FIGDIR/small/646387v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@876847org.highwire.dtl.DTLVardef@1cf2e69org.highwire.dtl.DTLVardef@f02df9org.highwire.dtl.DTLVardef@5a3f1f_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2022

Elucidating the systemic response of wheat plants under waterlogging based on transcriptomic and metabolic approaches

Extreme weather conditions lead to significant imbalances in crop productivity, which in turn affect food security. Flooding events cause serious problems to many crop species such as wheat. Although metabolic readjustments under flooding are important for plant regeneration, underlying processes remain poorly understood. Here, we investigated the systemic response of wheat to waterlogging using metabolomics and transcriptomics. A 12-day exposure to excess water triggered nutritional imbalances and disruption of metabolite synthesis and translocation, reflected by reduction of plant biomass and growth performance. Metabolic and transcriptomic profiling in roots, xylem, and leaves indicated anaerobic fermentation processes as a local response occurring in roots. Differentially expressed genes and ontological categories revealed that carbohydrate metabolism plays an important role as a systemic response. Analysis of the translocation rate of specific compounds in the xylem showed how waterlogging alters the composition of xylem exudates and thus the root to shoot communication. Interestingly, among all metabolites determined in our study, alanine was the most abundant transported in the xylem. Our results suggest an important role of this amino acid not only as amino-nitrogen source but also as the major root-to-shoot translocated and systemically acting metabolite crucial for balancing C/N between roots and shoots during waterlogging. The relevance of this study relies on the basis to characterize the important role of alanine as HighlightMetabolic and transcriptomic changes in wheat highlight alanine as the major root-to-shoot translocated and systemically acting metabolite crucial for balancing C/N between roots and shoots.

physiology↗

bioRxiv2021

Transcriptional dynamics of methane-cycling microbiomes are linked to seasonal CH4 fluxes in two hydromorphic and organic-rich grassland soils

Soil CH4 fluxes are driven by CH4-producing and -consuming microorganisms that determine whether soils are sources or sinks of this potent greenhouse gas. Using quantitative metatranscriptomics, we linked CH4-cycling microbiomes to net surface CH4 fluxes throughout a year in two drained peatland soils differing in grassland land-use intensity and physicochemical properties. CH4 fluxes were highly dynamic; both soils were net CH4 sources in autumn and winter and sinks in spring and summer. Despite similar net CH4 emissions, methanogen and methanotroph loads, as determined by small subunit rRNA transcripts per gram soil, differed strongly between sites. In contrast, mRNA transcript abundances were similar in both soils and correlated well with CH4 fluxes. The methane monooxygenase to methanogenesis mRNA ratio was higher in spring and summer, when the soils were net CH4 sinks. CH4 uptake was linked to an increased proportion of USC and {gamma} and pmoA2 pmoA transcripts. We assume that methanogen transcript abundance may be useful to approximate changes in net surface CH4 emissions from drained peat soils; high methanotroph to methanogen ratios would indicate CH4 sink properties. Our study shows the strength of quantitative metatranscriptomics; mRNA transcript abundance holds promising indicator to link soil microbiome functions to ecosystem-level processes.

microbiology↗