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Boeglin, L.

Publications and source records attributed to Boeglin, L..

3 recordsLinked to original sources

Deep learning enables quantitative subcellular analysis of plant-microbe interfaces

Specialized host-microbe interfaces are central to cellular interactions in plants. Intracellular structures such as haustoria formed by filamentous pathogens mediate nutrient exchange and effector delivery to host cells. Despite their biological importance, the lack of quantitative frameworks has largely confined the study of these interfaces to qualitative observations, limiting our ability to compare infection strategies, cellular responses, and spatial organization across cells and tissues. Here, we present HFinder, a deep learning-based framework for automated detection, segmentation, and quantitative analysis of plant-microbe interfaces in confocal images. Using an object-centric deep learning approach, HFinder enables robust identification of haustoria, microbial hyphae, and host organelles across diverse imaging conditions and pathosystems. We demonstrate that this framework supports quantitative analyses of subcellular processes at host-microbe interfaces, including effector secretion, perturbation of host cellular processes, and immune receptor accumulation at haustoria. HFinder provides a practical and scalable solution for the systematic digitalization of plant infection imaging data and establishes a general framework for quantitative studies of cellular dynamics at host-microbe contact zones.

cell biology↗

CodonBERT: Large Language Models for mRNA Design and Optimization

AO_SCPLOWBSTRACTC_SCPLOWmRNA based vaccines and therapeutics are gaining popularity and usage across a wide range of conditions. One of the critical issues when designing such mRNAs is sequence optimization. Even small proteins or peptides can be encoded by an enormously large number of mRNAs. The actual mRNA sequence can have a large impact on several properties including expression, stability, immunogenicity, and more. To enable the selection of an optimal sequence, we developed CodonBERT, a large language model (LLM) for mRNAs. Unlike prior models, CodonBERT uses codons as inputs which enables it to learn better representations. CodonBERT was trained using more than 10 million mRNA sequences from a diverse set of organisms. The resulting model captures important biological concepts. CodonBERT can also be extended to perform prediction tasks for various mRNA properties. CodonBERT outperforms previous mRNA prediction methods including on a new flu vaccine dataset.

bioinformatics↗

Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates

An effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority1. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.

immunology↗