Biology subjects

Murray, C. J.

Publications and source records attributed to Murray, C. J..

3 recordsLinked to original sources

bioRxiv2025

LICHEN: Light-chain Immunoglobulin sequence generation Conditioned on the Heavy chain and Experimental Needs

In developing therapeutic antibodies, the heavy chain is often prioritised due to its higher variability and its central role in antigen binding. An appropriate pairing of the light sequence is however important for antibody function. Here we present LICHEN, a heavy chain conditioned light sequence generation tool that enables collaborative light sequence design by leveraging computational capabilities alongside experimental expertise. LICHEN generates light sequences which are valid (antibodylike), diverse in sequence and structure, and conditioned on a specific heavy chain. LICHEN can also condition on germline and CDRs and automatically filter generated sequences for required properties. This allows LICHEN to be used across multiple antibody development use cases. We carry out experimental validation of the method conditioning only on the heavy sequence and on the heavy sequence and binding information. Our in vitro results show that sequences created by LICHEN have effective expression yields and can retain antigen-binding.

bioinformatics↗

bioRxiv2024

Dark Microglia Are Abundant in Normal Postnatal Development, where they Remodel Synapses via Phagocytosis and Trogocytosis, and Are Dependent on TREM2

This study examined dark microglia--a state linked to central nervous system pathology and neurodegeneration--during postnatal development in the mouse ventral hippocampus, finding that dark microglia interact with blood vessels and synapses and perform trogocytosis of pre-synaptic axon terminals. Furthermore, we found that dark microglia in development notably expressed C-type lectin domain family 7 member A (CLEC7a), lipoprotein lipase (LPL) and triggering receptor expressed on myeloid cells 2 (TREM2) and required TREM2, differently from other microglia, suggesting a link between their role in remodeling during development and central nervous system pathology. Together, these results point towards a previously under-appreciated role for dark microglia in synaptic pruning and plasticity during normal postnatal development.

neuroscience↗

bioRxiv2024

A comparison of microglial morphological complexity analysis in adult mouse brain samples using 2-dimensional and 3-dimensional image analysis tools

Characterizing cell morphology has been an essential aspect of neuroscience for over a century to provide essential insights into cellular function and dysfunction. Microglia, the resident innate immune cells of the central nervous system, undergo drastic changes in morphology in response to various stimuli, with many classifications proposed in recent years. Increased availability of advanced analysis software to study microglial morphology represents a step forward in the field. However, whether the use of advanced analysis tools provides equivalent or varied outcomes remains undetermined. This study re-analyzed raw data, previously processed using a standard 2D microglial morphology analysis method, using 3D analysis methods. The published article observed significant changes in microglial morphology in the mouse ventral hippocampus after administration of a ketogenic diet and exposure to repeated social defeat stress in young adult male mice. Overall, we observed different statistical outcomes in the 3D dataset compared to the previously published 2D results, with both maintained and new findings. This may indicate that the 3D analysis method is better able to capture minute changes in morphology. However, overall conclusions on microglial morphology changes remain consistent between methods. Lastly, we highlight the difference between a nested statistical design, which considers within animal variability, and a non-nested design. Overall, we highlight and discuss differences between 2D and 3D microglial morphology analysis and explore the contribution of individual cell and animal variability to statistical outcomes. Main PointsO_LI3D analysis method generates similar and novel results compared to a 2D method. C_LIO_LIverall microglial morphological changes to stimuli are comparable between methods. C_LIO_LInested statistical design produces distinct significant differences. C_LI

neuroscience↗