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Training the next cohort of bioimaging data stewards
No full textWorking with biological images can pose significant challenges requiring research technical professionals (RTPs) with appropriate technical expertise. This project aims to address these by working to build image data stewardship skills, role recognition and career pathways within the UK community. We will provide direct training support for RTPs integrating their data generation, curation and annotation work into the permanent scientific record. After a succession of events where the community was able to share their challenges and give their feedback, we have proposed a comprehensive curriculum in image data management and stewardship, and plan to deliver it via on-demand courses and in-person workshops.Poster presented as part of the Crick BioImage Analysis Symposium 2025.Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.</p
Engineered neural tissue (EngNT) containing human iPSC-derived Schwann cell precursors promotes axon growth in a rat model of peripheral nerve injury
No full textTissue engineering has the potential to overcome the limitations of using autografts in nerve gap repair, using cellular biomaterials to bridge the gap and support neuronal regeneration. Various types of therapeutic cells could be considered for use in aligned collagen-based engineered neural tissue (EngNT), including Schwann cells and their precursors, which can be derived from human induced pluripotent stem cells (hiPSCs). Using Schwann cell precursors may have practical advantages over mature Schwann cells as they expand readily in vitro and involve a shorter differentiation period. However, the performance of each cell type needs to be tested in EngNT. By adapting established protocols, hiPSCs were differentiated into Schwann cell precursors and Schwann cells, with distinctive molecular profiles confirmed using immunocytochemistry and RT-qPCR. For the first time, both cell types were incorporated into EngNT using gel aspiration–ejection, a technique used to align and simultaneously stabilise the cellular hydrogels. Both types of cellular constructs supported and guided aligned neurite outgrowth from adult rat dorsal root ganglion neurons in vitro. Initial experiments in a rat model of nerve gap injury demonstrated the extent to which the engrafted cells survived after 2 weeks and indicated that both types of hiPSC-derived cells supported the infiltration of host neurons, Schwann cells and endothelial cells. In summary, we show that human Schwann cell precursors promote infiltrating endogenous axons in a model of peripheral nerve injury to a greater degree than their terminally differentiated Schwann cell counterparts
Microscopy Nodes: 3D data visualization in Blender
No full textPoster presented as part of the Crick BioImage Analysis Symposium 2025.Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.</p
Hybrid Hydrogels for Tissue Mimics: Multimodal native imaging to understand structure and cell interactions
No full text• Periodontitis is one of the most common chronic inflammatory diseases worldwide (>50% of the population — Image 2)• Bacterial plaque + gum inflammation & imbalance in the microbiome • Irreversible damage: soft tissue & bone degradation, tooth loss, impact on quality of life (Image 1) • Risk factors: poor oral hygiene, smoking, and genetic predisposition • Correlated with and influences systemic diseases ex: cancers, obstetric and cardiovascular conditions Poster presented as part of the Crick BioImage Analysis Symposium 2025.Permission has been given by authors to upload to Crick Figshare. Copyright remains with the original authors.</p
Horizontal acquisition of prokaryotic hopanoid biosynthesis reorganizes membrane physiology driving lifestyle innovation in a eukaryote.
No full textHorizontal gene transfer is a source of metabolic innovation and adaptation to new environments. How new metabolic functionalities are integrated into host cell biology is largely unknown. Here, we probe this fundamental question using the fission yeast Schizosaccharomyces japonicus, which has acquired a squalene-hopene cyclase Shc1 through horizontal gene transfer. We show that Shc1-dependent production of hopanoids, mimics of eukaryotic sterols, allows S. japonicus to thrive in anoxia, where sterol biosynthesis is not possible. We demonstrate that glycerophospholipid fatty acyl asymmetry, prevalent in S. japonicus, is crucial for accommodating both sterols and hopanoids in membranes and explain how Shc1 functions alongside the sterol biosynthetic pathway to support membrane properties. Reengineering experiments in the sister species S. pombe show that hopanoids entail new traits in a naïve organism, but the acquisition of a new enzyme may trigger profound reorganization of the host metabolism and physiology
Divergent DNA methylation dynamics in marsupial and eutherian embryos.
No full textBased on seminal work in placental species (eutherians)1-10, a paradigm of mammalian development has emerged wherein the genome-wide erasure of parental DNA methylation is required for embryogenesis. Whether such DNA methylation reprogramming is, in fact, conserved in other mammals is unknown. Here, to resolve this point, we generated base-resolution DNA methylation maps in gametes, embryos and adult tissues of a marsupial, the opossum Monodelphis domestica, revealing variations from the eutherian-derived model. The difference in DNA methylation level between oocytes and sperm is less pronounced than that in eutherians. Furthermore, unlike the genome of eutherians, that of the opossum remains hypermethylated during the cleavage stages. In the blastocyst, DNA demethylation is transient and modest in the epiblast. However, it is sustained in the trophectoderm, suggesting an evolutionarily conserved function for DNA hypomethylation in the mammalian placenta. Furthermore, unlike that in eutherians, the inactive X chromosome becomes globally DNA hypomethylated during embryogenesis. We identify gamete differentially methylated regions that exhibit distinct fates in the embryo, with some transient, and others retained and that represent candidate imprinted loci. We also reveal a possible mechanism for imprinted X inactivation, through maternal DNA methylation of the Xist-like noncoding RNA RSX11. We conclude that the evolutionarily divergent eutherians and marsupials use DNA demethylation differently during embryogenesis
DiffCom22Oct-5Nov_SAGperturbations
No full textDifferentiations from 5th Nov and 22nd October with SAG perturbations "UpSAG" (24h 0nM SAG, followed by 500 nM SAG) or "DownSAG" (24h 500 nM SAG, followed by 0 nM SAG). </p
NeuralProg_DiffCom30Oct
No full textDifferentiation from 30 October. Constant SAG at different concentrations.</p
Clinical referral to the NHS following multi-cancer early detection test results from the NHS-Galleri trial.
No full textINTRODUCTION: The large, randomised, controlled NHS-Galleri trial (NCT05611632) is assessing the clinical utility of a multi-cancer early detection (MCED) test for asymptomatic cancer screening in England. We describe how we enabled the efficient referral of trial participants into existing National Health Service (NHS) urgent suspected cancer pathways for diagnostic investigations. METHODS/RESULTS: Participants were enrolled across eight of the 21 Cancer Alliance regions in England, served by 56 Hospital Trusts. We used the existing NHS e-Referral Service (e-RS) and a new e-referral form to enable referrals from the trial into any participating Trust, and to standardise information provided with trial participant referrals. Referrals were made by trial nurses directly into secondary care, minimising any additional burden on primary care. At most Trusts, a designated Trust-based referral coordinator triaged referrals and referred participants into the most appropriate local pathway, selected based on the tissue type or organ associated with the cancer signal (cancer signal origin; CSO). At other Trusts, trial nurses referred participants into the appropriate pathway. Guidance mapping predicted CSO(s) to NHS pathways was provided by the trial team to help clinicians understand trial referrals. The trial team and Trust referral coordinators were responsible for central and Trust-level safety netting measures, respectively. CONCLUSIONS: To our knowledge, the NHS-Galleri trial has established the first model for the standardised clinical referral of asymptomatic individuals from a trial into NHS standard-of-care cancer pathways. We hope insights from our work could help accelerate screening trial conduct in the UK, and support MCED population screening programme implementation in future
Bacterial effectors mediate kinase reprogramming through mimicry of conserved eukaryotic motifs.
No full textBacteria have evolved numerous biochemical processes that underpin their biology and pathogenesis. The small, non-enzymatic bacterial (Salmonella) effector SteE mediates kinase reprogramming, whereby the canonical serine/threonine host kinase GSK3 gains tyrosine-directed activity towards neosubstrates, promoting Salmonella virulence. Yet, both the mechanism behind the switch in GSK3's activity and the diversity of this phenomenon remain to be determined. Here we show that kinase reprogramming of GSK3 is mediated by putative homologues from diverse Gram-negative pathogens. Next, we identify both the molecular basis of how SteE targets GSK3 and uncover that the SteE-induced tyrosine activity conferred on GSK3 requires an L/xGxP motif. This motif, found in several CMGC kinases that undergo auto-tyrosine phosphorylation, was previously shown to mediate GSK3 autophosphorylation on a tyrosine. Together, we suggest that the SteE family of intrinsically disordered proteins mediates kinase reprogramming via several short linear motifs that each appear to mimic eukaryotic signalling motifs. With this insight comes the potential for the rationale design of synthetic reprogramming proteins