5683099 research outputs found
Sort by
Results of the protein engineering tournament: An open science benchmark for protein modeling and design.
No full textThe grand challenge of protein engineering is the development of computational models to characterize and generate protein sequences for arbitrary functions. Progress is limited by lack of (1) benchmarking opportunities, (2) large protein function datasets, and (3) access to experimental protein characterization. We introduce the Protein Engineering Tournament-a fully-remote competition designed to foster the development and evaluation of computational approaches in protein engineering. The tournament consists of a predictive round, predicting biophysical properties from protein sequences, followed by a generative round where novel protein sequences are designed, expressed, and characterized using automated methods. Upon completion, all datasets, experimental protocols, and methods are made publicly available. We detail the structure and outcomes of a pilot Tournament involving seven protein design teams, powered by six multi-objective datasets, with experimental characterization by our partner, International Flavors and Fragrances. Forthcoming Protein Engineering Tournaments aim to mobilize the scientific community towards transparent evaluation of progress in the field
A Euro-BioImaging Scientific Ambassador's Role in Strengthening Research Communities
No full textThe Euro-Biolmaging Scientific Ambassadors program aims to raise awareness about the services and opportunities provided by Euro-Biolmaging. Our Scientific Ambassadors act as catalysts, connecting with like-minded individuals who share a common goal to impact in their communities. By effectively communicating the services offered by Euro-Biolmaging, our Scientific Ambassadors play a crucial role in expanding the reach of Euro-Biolmaging. Through their advocacy and engagement, Scientific Ambassadors help foster a greater understanding of Euro-Biolmaging services, making imaging technologies more accessible for researchers and creating opportunities for collaboration, scientific advancement, and innovation in bioimaging. </p
Enhancing research through image analysis workshops:experiences and best practices
No full textModern microscopy systems allow researchers to generate large volumes of image data with relative ease. However, the challenge of analyzing these data effectively is often hindered by a lack of computational skills. This bottleneck negatively impacts both research reproducibility and efficiency, as researchers frequently rely on manual or semi-automated analysis methods. Interactive image analysis workshops offer a valuable solution, equipping researchers with the skills and tools needed to automate image processing tasks. In this paper,we share our experiences and best practices from conducting such workshops,which emphasize the use of open-source software like ImageJ, FIJI, and Python-based tools such as JupyterLab and napari. We discuss key considerations for workshop design, logistics, and outcomes, while highlighting common pitfalls to avoid. Using two recent workshops as case studies, we also present strategies for optimizing participant engagement and learning. Our insights offer practical guidance for planning and conducting image analysis workshops and serve as a starting point for researchers looking to establish similar training initiatives and enrich their local imaging communities.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
The first Drosophila wing imaginal disc atlas
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
Timely TGFβ signalling inhibition induces notochord.
No full textThe formation of the vertebrate body involves the coordinated production of trunk tissues from progenitors located in the posterior of the embryo. Although in vitro models using pluripotent stem cells replicate aspects of this process1-10, they lack crucial components, most notably the notochord-a defining feature of chordates that patterns surrounding tissues11. Consequently, cell types dependent on notochord signals are absent from current models of human trunk formation. Here we performed single-cell transcriptomic analysis of chick embryos to map molecularly distinct progenitor populations and their spatial organization. Guided by this map, we investigated how differentiating human pluripotent stem cells develop a stereotypical spatial organization of trunk cell types. We found that YAP inactivation in conjunction with FGF-mediated MAPK signalling facilitated WNT pathway activation and induced expression of TBXT (also known as BRA). In addition, timely inhibition of WNT-induced NODAL and BMP signalling regulated the proportions of different tissue types, including notochordal cells. This enabled us to create a three-dimensional model of human trunk development that undergoes morphogenetic movements, producing elongated structures with a notochord and ventral neural and mesodermal tissues. Our findings provide insights into the mechanisms underlying vertebrate notochord formation and establish a more comprehensive in vitro model of human trunk development. This paves the way for future studies of tissue patterning in a physiologically relevant environment
TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.
No full textChromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency. FAT1 ablation causes persistent replication stress, an elevated mitotic failure rate, nuclear deformation and elevated structural CIN, including chromosome translocations and radial chromosomes. FAT1 loss contributes to whole-genome doubling (a form of numerical CIN) through the dysregulation of YAP1. Co-depletion of YAP1 partially rescues numerical CIN caused by FAT1 loss but does not relieve HR deficiencies, nor structural CIN. Importantly, overexpression of constitutively active YAP15SA is sufficient to induce numerical CIN. Taken together, we show that FAT1 loss in NSCLC attenuates HR and exacerbates CIN through two distinct downstream mechanisms, leading to increased tumour heterogeneity
Focal deletions of a promoter tether activate the IRX3 oncogene in T-cell acute lymphoblastic leukemia.
No full textOncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T cell acute lymphoblastic leukemia (T-ALL). Loss of this CTCF bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (-644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that 'promoter tethering' of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis
Intrinsic electrical activity drives small-cell lung cancer progression.
No full textElevated or ectopic expression of neuronal receptors promotes tumour progression in many cancer types1,2; neuroendocrine (NE) transformation of adenocarcinomas has also been associated with increased aggressiveness3. Whether the defining neuronal feature, namely electrical excitability, exists in cancer cells and impacts cancer progression remains mostly unexplored. Small-cell lung cancer (SCLC) is an archetypal example of a highly aggressive NE cancer and comprises two major distinct subpopulations: NE cells and non-NE cells4,5. Here we show that NE cells, but not non-NE cells, are excitable, and their action potential firing directly promotes SCLC malignancy. However, the resultant high ATP demand leads to an unusual dependency on oxidative phosphorylation in NE cells. This finding contrasts with the properties of most cancer cells reported in the literature, which are non-excitable and rely heavily on aerobic glycolysis. Additionally, we found that non-NE cells metabolically support NE cells, a process akin to the astrocyte-neuron metabolite shuttle6. Finally, we observed drastic changes in the innervation landscape during SCLC progression, which coincided with increased intratumoural heterogeneity and elevated neuronal features in SCLC cells, suggesting an induction of a tumour-autonomous vicious cycle, driven by cancer cell-intrinsic electrical activity, which confers long-term tumorigenic capability and metastatic potential
Annual (2024) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota).
No full textIn April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished. This article presents the updated taxonomy of Negarnaviricota as currently accepted by the ICTV, providing an essential annual update on the classification of members of this phylum that deepen understandings of their evolution, and supports critical public health measures for virus identification and tracking
Analysis of research data management policies in UK HEI: code and data
No full textR code, input data and output figures from "Do data management policies become more open over time?"Code is for Mann Kendal tests, Spearman correlations and Anova tests. The analyses are to determine if policies and policy language change over time. They are hardcoded to the specific terms used in this analysis but could be altered to be used for other similar analysis.Data and Figures are licensed under CC BY 4.0.</p