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Foerster, S.

Publications and source records attributed to Foerster, S..

6 recordsLinked to original sources
bioRxiv2025

Myelin Basic Protein Binding Is Modulated by Leaflet Asymmetry and Lipid Composition

Compositional asymmetry between lipid bilayer leaflets is a defining feature of biological membranes, yet its role in modulating protein binding remains largely unexplored. Here, we investigate how leaflet-specific composition affects the interaction between Myelin Basic Protein and biomimetic myelin membranes using neutron reflectometry. Asymmetric supported myelin bilayers containing deuterated cholesterol in the cytoplasmic leaflet enabled resolution of structural asymmetry. Neutron reflectometry measurements show that Myelin Basic Protein binds preferentially to asymmetric supported bilayers mimicking native myelin, whereas Experimental Autoimmune Encephalomyelitis-modified compositions exhibit weaker binding and more pronounced protein insertion. Disruption of asymmetry--either by thermal-induced lipid redistribution or by using symmetric cytoplasmic myelin--leads to a marked reduction in Myelin Basic Protein binding, despite increased membrane charge. Following vesicle adsorption and formation of a second bilayer, the protein layer narrows to near in vivo thickness in both systems, with the diseased condition exhibiting a wider inter-bilayer spacing. These results underscore the relevance of lipid asymmetry and composition in governing protein - membrane interactions, with implications for the molecular basis of myelin stability and demyelination.

biophysics↗
bioRxiv2025

Age-related changes in behavioral and neural variability in a decision-making task

Age-related cognitive decline in learning and decision-making may arise from increased variability of neural responses. Here, we investigated how ageing affects behavioural and neural variability by recording >18,000 neurons across 16 brain regions (including cortex, hippocampus, thalamus, midbrain, and basal ganglia) in younger and older mice performing a visual decision-making task. Older mice showed more variable response times, reproducing a common finding in human ageing studies. Ageing globally increased firing rates and post-stimulus neural variability (quantified using the Fano factor), and decreased variability quenching-the reduction in neural variability upon stimulus presentation. Older animals showed higher overall firing rates across areas of visual and motor cortex, striatum, midbrain, and hippocampus, but lower firing rates in thalamic areas. Age-related attenuation in stimulus-induced variability quenching was most prominent in visual and motor cortex, striatum, and thalamic area. These findings show how large-scale neural recordings can help uncover regional specificity of ageing effects in single neurons, ultimately improving our understanding of the neural basis of age-related cognitive decline.

neuroscience↗
bioRxiv2020

Proliferation is a requirement for differentiation of oligodendrocyte progenitor cells during CNS remyelination

Oligodendrocytes that generate new myelin sheaths around demyelinated axons in the regenerative process of remyelination are generally derived from oligodendrocyte progenitor cells (OPCs). During this process, OPCs become activated, populate the area of myelin loss, and finally differentiate. Although much is known about the individual stages of remyelination, the exact sequence of events and whether a dependency of each individual stage on each other exists is unknown. Understanding the biology behind these questions is important for the development of remyelination therapies to overcome the age-related decline in remyelination efficiency observed in the chronic phase of multiple sclerosis (MS). Here we show that, following toxin-induced demyelination, all re-populating OPCs first migrate into the site of damage, undergo relatively few rounds of division and eventually differentiate. We further show that OPC proliferation is a requirement for differentiation. Together, our results reveal an unexpected link between OPC proliferation and differentiation, and opens up the possibility of novel regenerative strategies in MS focussing on stimulating OPC proliferation.

neuroscience↗
bioRxiv2019

Specific oligodendrocyte populations have differential spatial distribution and susceptibility to injury

Oligodendrocytes (OLs), the myelinating cells of the central nervous system, are transcriptionally heterogeneous,1 the origin and functional consequences of which are unknown. Functional heterogeneity of MOLs might correlate with the local environment or their interactions with different neuron types.2 Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system and differential susceptibility to traumatic spinal cord injury. We also show that the generation of distinct MOL populations is independent of the OPC developmental origin. We found that OPCs originating from the previously described developmental waves3-5 have comparable potential to differentiate into the main MOL populations. Furthermore, we found that MOL type 2 (MOL2) is enriched in the spinal cord and almost absent in the brain, while MOL5/6 is enriched with age in all analyzed regions. MOL2 and MOL5/6 also have differential preference for motor and sensory tracts in the spinal cord. In the context of disease, we found that MOL2 and MOL5/6 have differential susceptibility to traumatic spinal cord injury, where MOL2 are lost and MOL5/6 increased their contribution to the OL lineage. Importantly, MOL2 susceptibility is disease specific, as we found MOL2 is not lost in a mouse model of multiple sclerosis. Our results demonstrate that the MOL populations, previously described by single-cell transcriptomics,1 have distinct spatial preference and responses. We anticipate our study to pave the way for a better understanding of the MOL populations-specific functional roles in development, health, and disease, allowing for better targeting of the OL subtypes important for the regeneration and repair of the central nervous system.

neuroscience↗
bioRxiv2018

Oxford Nanopore MinION genome sequencer: performance characteristics, optimised analysis workflow, phylogenetic analysis and prediction of antimicrobial resistance in Neisseria gonorrhoeae

Antimicrobial resistant (AMR) Neisseria gonorrhoeae strains are common and compromise gonorrhoea treatment internationally. Rapid identification and characterisation of AMR gonococcal strains could ensure appropriate and even personalised treatment, and support identification and investigation of gonorrhoea outbreaks in nearly real-time. Whole-genome sequencing is ideal for investigation of the emergence and dissemination of AMR determinants that predict AMR in the gonococcal population and spread of AMR strains in the human population. The novel, rapid and revolutionary long-read sequencer MinION is a small hand-held device that can generate bacterial genomes within one day. However, the accuracy of MinION reads has been suboptimal for many objectives and the MinION has not been evaluated for gonococci. In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants. Nevertheless, using an in house-developed CLC Genomics Workbench, we show that ONT-derived sequences can be used for accurate prediction of decreased susceptibility or resistance to recommended therapeutic antimicrobials. We also show that the ONT-derived sequences can be useful for rapid phylogenomic-based molecular epidemiological investigations, and, in hybrid assemblies with Illumina sequences, for producing contiguous assemblies and finished reference genomes.

genomics↗