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Biology subjects

Gabriel, J.

Publications and source records attributed to Gabriel, J..

6 recordsLinked to original sources

Morphomolecular Longitudinal Endoscopy of Carcinogenesis

Current diagnostic approaches for head and neck cancer rely primarily on white-light endoscopy and tissue biopsy, providing only static, episodic assessments that fail to capture dynamic changes in tumour biology over time. This absence of continuous, detailed molecular and microscopic structural information makes early identification of dysplasia or cancer difficult and can delay critical treatment. Here, we introduce a unified, label-free endoscopic platform that combines Raman spectroscopy (RS) and optical coherence tomography (OCT) within a miniaturised, forward-viewing fibre-optic probe. This integration enables simultaneous video-rate OCT imaging and subsecond RS acquisition linking morphological and molecular tissue trajectories in vivo. We developed an explainable AI-based fusion framework that learns joint temporal representations of biochemical and structural features to classify tissue states while highlighting the most influential predictors. In a longitudinal 4NQO-induced murine model of carcinogenesis, the system tracked epithelial transformation in real-time from hyperplasia through dysplasia to neoplasia. By capturing temporally resolved morphomolecular trajectories in vivo, this platform establishes a new paradigm for early cancer detection and real-time surveillance, supporting timely and individualised clinical decision-making.

bioengineering↗

Multi-scale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this we have created a multi-scale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single cell RNA sequencing, spatial global transcriptional profiling and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community. Significance statementSingle cells RNA sequencing has revolutionised cell biology, enabling high resolution analysis of cell types and states within human tissues. Here, we report a comprehensive spatial atlas of adult human skin across different anatomical sites and basal cell carcinoma (BCC) - the most common form of skin cancer - encompassing in vivo optical coherence tomography, single cell RNA sequencing, global spatial transcriptomic profiling and in situ sequencing. In combination these modalities have allowed us to assemble a comprehensive nuclear-resolution atlas of cellular identity in health and disease.

cell biology↗

Alpaca Single B Cell Interrogation and Heavy-Chain-Only Antibody Discovery on an Optofluidic Platform

In vivo discovery approaches for single domain antibodies such as VHH have been limited by the lack of methodologies available for camelid B cell interrogation. Here, we report a novel application of the Berkeley Lights Beacon(R) optofluidic platform to the discovery of heavy-chain-only antibodies by screening single B cells from alpacas immunized with two different targets. Custom methods for alpaca B cell enrichment, culture, on-Beacon IgG2/3 detection, and sequencing were developed and used to discover target-specific VHH candidates from an alpaca immunized with either human prostate specific membrane antigen (PSMA) or a second blinded target, in a proof-of-concept study. PSMA-specific VHH hits discovered on the Beacon were recombinantly expressed as VHH-Fc, purified, and characterized using label-free techniques. All but one VHH-Fc bound PSMA with a single-digit nanomolar affinity, and four candidates were successfully humanized in silico using a rapid bulk humanization approach. In addition, next-generation repertoire sequencing was performed at longitudinal timepoints after immunization, uncovering additional variants within the clonal lineages of the validated hits discovered on the Beacon platform. The establishment of this single B cell VHH discovery workflow extends the powerful Beacon technology to enable rapid discovery of VHH directly from natural camelid immune repertoires.

immunology↗

Accelerated Antibody Discovery Targeting the SARS-CoV-2 Spike Protein for COVID-19 Therapeutic Potential

Rapid deployment of technologies capable of high-throughput and high-resolution screening is imperative for timely response to viral outbreaks. Risk mitigation in the form of leveraging multiple advanced technologies further increases the likelihood of identifying efficacious treatments in an aggressive timeline. In this study, we describe two parallel, yet distinct, in vivo approaches for accelerated discovery of antibodies targeting the SARS-CoV-2 spike protein. Working with human transgenic Alloy-GK mice, we detail a single B-cell discovery workflow to directly interrogate antibodies secreted from plasma cells for binding specificity and ACE2 receptor blocking activity. Additionally, we describe a concurrent accelerated hybridoma-based workflow utilizing a DiversimAb mouse model for increased diversity. The panel of antibodies isolated from both workflows revealed binding to distinct epitopes with both blocking and non-blocking profiles. Sequence analysis of the resulting lead candidates uncovered additional diversity with the opportunity for straightforward engineering and affinity maturation. By combining in vivo models with advanced integration of screening and selection platforms, lead antibody candidates can be sequenced and fully characterized within one to three months.

immunology↗

Phylogeny, morphology and the role of hybridization as driving force of evolution in grass tribes Aveneae and Poeae (Poaceae)

To investigate the evolutionary diversification and morphological evolution of grass supertribe Poodae (subfam. Pooideae, Poaceae) we conducted a comprehensive molecular phylogenetic analysis including representatives from most of their accepted genera. We focused on generating a DNA sequence dataset of plastid matK gene-3trnK exon and trnL- trnF regions and nuclear ribosomal ITS1-5.8S gene-ITS2 and ETS that was taxonomically overlapping as completely as possible (altogether 257 species). The idea was to infer whether phylogenetic trees or certain clades based on plastid and nuclear DNA data correspond with each other or discord, revealing signatures of past hybridization. The datasets were analysed using maximum parsimony, maximum likelihood and Bayesian approaches. Instances of severe conflicts between the phylogenetic trees derived from both datasets, some of which have been noted earlier, unambiguously point to hybrid origin of several lineages (subtribes, groups of genera, sometimes genera) such as Phalaridinae, Scolochloinae, Sesleriinae, Torreyochloinae; Arctopoa, Castellia, Graphephorum, Hyalopodium, Lagurus, Macrobriza, Puccinellia plus Sclerochloa, Sesleria, Tricholemma, American Trisetum, etc. and presumably Airinae, Holcinae and Phleinae. Calamagrostis flavens appears to be an intergeneric hybrid between Agrostis and Calamagrostis. Most frequently there is good agreement of other regions of the trees, apart from intrinsic different phylogenetic resolution of the respective DNA markers. To explore the to date rather unclear morphological evolution of our study group a data matrix encompassing finally 188 characters was analysed for ancestral state reconstructions (ASR) using the tree from the combined molecular dataset as presumably best approximation to the species phylogeny. For 74 characters ASRs were feasible and yielded partly surprising results for the study group as a whole but also for some of their subdivisions. Considering taxonomy and classification it became evident, that many morphological characters show a very high degree of homoplasy and are seemingly able to change within comparatively short timespans in the evolution of our grasses. Most of the taxonomic units distinguished within our study group, e.g. as subtribes, are defined less by consistent morphological characters or character combinations and should be rather understood as clades revealed by molecular phylogenetic analysis. One reason for this extreme homoplasy concerning traditionally highly rated characters of inflorescences or spikelets and their components might be that they have little to do with pollination (always wind) or adaptation to pollinators as in other angiosperms but rather with dispersal and diaspores. Easily changing structure of spikelet disarticulation, of glume, lemma or awn characters might be advantageous in the rapid adaptation to different habitats and micro-habitats, which was evidently most successfully accomplished by these grasses. A partly revised classification of Poodae is presented, including a re-instatement of tribes Aveneae and Poeae s.str. Following a comparatively narrow delineation of preferably monophyletic subtribes, Antinoriinae, Avenulinae, Brizochloinae, Helictochloinae, Hypseochloinae are described as new. New genera are Arctohyalopoa and Hyalopodium. New combinations are Arctohyalopoa lanatiflora, A. lanatiflora subsp. ivanoviae, A. lanatiflora subsp. momica, Colpodium biebersteinianum, C. kochii, C. trichopodum, C. verticillatum, Deschampsia micrathera, Dupontia fulva, Festuca masafuerana, Hyalopodium araraticum, Paracolpodium baltistanicum, Parapholis cylindrica, P. xpauneroi. Festuca masatierrae is a new name.\n\nSupporting Information may be found online in the Supporting Information section at the end of the article.

plant biology↗

Recovery of the type specimen of Avena breviaristata, an endemic Algerian grass species collected only once (1882): morphology, taxonomy and botanical history

Avena breviaristata, collected only once (1882) in Algeria and never re-collected since, is a very mysterious grass species because unfortunately even the type specimen got lost 60--80 years ago. Morphological information on this species was thus based on a few published descriptions, which made it difficult, however, to correctly infer the genus affiliation of this morphologically odd species. Avena breviaristata became affiliated in the past with various oat-like genera (Avenula, Helictotrichon, Tricholemma). Due to the recent rediscovery of the type specimen at the P herbarium and the opportunity to study this specimen, we report here on the morphological characters of A. breviaristata underpinned by meaningful illustrations. They are discussed in comparison with the morphology of representative species of the above-mentioned genera. Uncommon characters of the spikelets (type of disarticulation of the rachilla, lemma structure, lodicules) and to some extent of the inflorescences, leaves and leaf sheaths support the inclusion of A. breviaristata in the North African genus Tricholemma. Considering biogeography, T. breviaristatum from the arid Hauts Plateaux in Algeria is a highly xeromorphic counterpart of the mesomorphic species T. jahandiezii, which is confined to higher altitudes of the rather humid Moyen Atlas in Morocco. This underlines the status of Tricholemma as a relic endemic. Our morphological survey supports the classification of Avenula (only A. pubescens) as separate from Helictotrichon s.str. and Helictochloa. Moreover, morphological evidence does not support an origin of A. pubescens by intergeneric hybridization between the latter genera as hypothesized in some prior studies. Especially the glabrous palea, the special shape of the lodicules and the structure of the awn show no intermediacy. The complicated history of the type collection of T. breviaristatum and the role of botanical authors are given.

plant biology↗