Biology subjects

Schuhmacher, M.

Publications and source records attributed to Schuhmacher, M..

3 recordsLinked to original sources

bioRxiv2023

Gut microbiota and maternal immune transfer at birth influence pre-allergic clinical outcome.

The gut microbiota of 2-3 month-old infants is associated with later pre-allergic signs, while the microbiota at the time of allergic manifestation is not. We hypothesized that the infant gut microbiota and immune system are primed shortly after birth, and that this is influenced by maternal transfer of humoral immunity. We investigated the association between allergic outcomes and composition and humoral immunity to gut microbiota at birth, 2 months, and 2 years-of-age. Meconium microbiota clustered into three groups dominated by Escherichia, Enterococcus, and mixed genera, respectively. The Escherichia cluster was associated with protection against later allergic manifestations. We moreover studied the proportion and specificity of humoral immunity to gut microbiota. Humoral immunity to gut microbiota at birth was associated with future allergies. Future studies should evaluate whether interventions to alter gut microbiota and humoral immunity in early-life protects against allergy.

immunology↗

bioRxiv2023

Quantifying single cell lipid signaling kinetics after photo-stimulation

Studying the role of molecularly distinct lipid species in cell signaling remains challenging due to a scarcity of methods for performing quantitative lipid biochemistry in living cells. We have recently used lipid uncaging to quantify lipid-protein affinities and rates of lipid transbilayer movement and turnover in the diacylglycerol signaling pathway using population average time series data. So far, this approach does not allow to account for the cell-to-cell variability of cellular signaling responses. We here report a framework that allows to uniquely identify model parameters such diacylglycerol-protein affinities and transbilayer movement rates at the single cell level for a broad variety of structurally different diacylglycerol species. We find that lipid unsaturation degree and longer side chains generally correlate with faster lipid transbilayer movement and turnover and higher lipid-protein affinities. In summary, our work demonstrates how rate parameters and lipid-protein affinities can be quantified from single cell signaling trajectories with sufficient sensitivity to resolve the subtle kinetic differences caused by the chemical diversity of cellular signaling lipid pools.

cell biology↗

bioRxiv2019

Addressing lipid structural diversity in signalling: Photochemical probes for live-cell lipid biochemistry

Every cell produces thousands of distinct lipid species, but methodology for studying the biological roles of individual lipids is insufficient. Using the example of diacylglycerols, prominent second messengers, we here investigate whether lipid chemical diversity can provide a basis for cellular signal specification. We developed novel photo-caged lipid probes, which allow acute manipulation of distinct diacylglycerol species in the plasma membrane. Combining uncaging experiments with mathematical modelling enabled the determination of binding constants for diacylglycerol-protein interactions and kinetic parameters for diacylglycerol transbilayer movement and turnover in quantitative live-cell experiments. Strikingly, we find that affinities and kinetics vary by orders of magnitude due to diacylglycerol structural diversity. These differences are sufficient to explain differential recruitment of diacylglycerol binding proteins and thus differing downstream phosphorylation patterns. Our approach represents a generally applicable method for elucidating the biological function of single lipid species on subcellular scales.

biochemistry↗