Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins

BACKGROUND: Trisomy of human chromosome 21 (Chr21) results in Down's syndrome, a complex developmental and neurodegenerative disease. Molecular analysis of Down's syndrome, however, poses a particular challenge, because the aneuploid region of Chr21 contains many genes of unknown function. Subcellular localization of human Chr21 proteins may contribute to further understanding of the functions and regulatory mechanisms of the genes that code for these proteins. Following this idea, we used a transfected-cell array technique to perform a rapid and cost-effective analysis of the intracellular distribution of Chr 21 proteins. RESULTS: We chose 89 genes that were distributed over the majority of 21q, ranging from RBM11 (14.5 Mb) to MCM3AP (46.6 Mb), with part of them expressed aberrantly in the Down's syndrome mouse model. Open reading frames of these genes were cloned into a mammalian expression vector with an amino-terminal His(6 )tag. All of the constructs were arrayed on glass slides and reverse transfected into HEK293T cells for protein expression. Co-localization detection using a set of organelle markers was carried out for each Chr21 protein. Here, we report the subcellular localization properties of 52 proteins. For 34 of these proteins, their localization is described for the first time. Furthermore, the alteration in cell morphology and growth as a result of protein over-expression for claudin-8 and claudin-14 genes has been characterized. CONCLUSION: The cell array-based protein expression and detection approach is a cost-effective platform for large-scale functional analyses, including protein subcellular localization and cell phenotype screening. The results from this study reveal novel functional features of human Chr21 proteins, which should contribute to further understanding of the molecular pathology of Down's syndrome

Ten simple rules for making training materials FAIR

Author summary: Everything we do today is becoming more and more reliant on the use of computers. The field of biology is no exception; but most biologists receive little or no formal preparation for the increasingly computational aspects of their discipline. In consequence, informal training courses are often needed to plug the gaps; and the demand for such training is growing worldwide. To meet this demand, some training programs are being expanded, and new ones are being developed. Key to both scenarios is the creation of new course materials. Rather than starting from scratch, however, it’s sometimes possible to repurpose materials that already exist. Yet finding suitable materials online can be difficult: They’re often widely scattered across the internet or hidden in their home institutions, with no systematic way to find them. This is a common problem for all digital objects. The scientific community has attempted to address this issue by developing a set of rules (which have been called the Findable, Accessible, Interoperable and Reusable [FAIR] principles) to make such objects more findable and reusable. Here, we show how to apply these rules to help make training materials easier to find, (re)use, and adapt, for the benefit of all

iAnn: an event sharing platform for the life sciences

Summary: We present iAnn, an open source community-driven platform for dissemination of life science events, such as courses, conferences and workshops. iAnn allows automatic visualisation and integration of customised event reports. A central repository lies at the core of the platform: curators add submitted events, and these are subsequently accessed via web services. Thus, once an iAnn widget is incorporated into a website, it permanently shows timely relevant information as if it were native to the remote site. At the same time, announcements submitted to the repository are automatically disseminated to all portals that query the system. To facilitate the visualization of announcements, iAnn provides powerful filtering options and views, integrated in Google Maps and Google Calendar. All iAnn widgets are freely available. Availability: http://iann.pro/iannviewer Contact: [email protected]

Systems Biology in ELIXIR: modelling in the spotlight

In this white paper, we describe the founding of a new ELIXIR Community - the Systems Biology Community - and its proposed future contributions to both ELIXIR and the broader community of systems biologists in Europe and worldwide. The Community believes that the infrastructure aspects of systems biology - databases, (modelling) tools and standards development, as well as training and access to cloud infrastructure - are not only appropriate components of the ELIXIR infrastructure, but will prove key components of ELIXIR\u27s future support of advanced biological applications and personalised medicine. By way of a series of meetings, the Community identified seven key areas for its future activities, reflecting both future needs and previous and current activities within ELIXIR Platforms and Communities. These are: overcoming barriers to the wider uptake of systems biology; linking new and existing data to systems biology models; interoperability of systems biology resources; further development and embedding of systems medicine; provisioning of modelling as a service; building and coordinating capacity building and training resources; and supporting industrial embedding of systems biology. A set of objectives for the Community has been identified under four main headline areas: Standardisation and Interoperability, Technology, Capacity Building and Training, and Industrial Embedding. These are grouped into short-term (3-year), mid-term (6-year) and long-term (10-year) objectives

Ten simple rules for making training materials FAIR.

Everything we do today is becoming more and more reliant on the use of computers. The field of biology is no exception; but most biologists receive little or no formal preparation for the increasingly computational aspects of their discipline. In consequence, informal training courses are often needed to plug the gaps; and the demand for such training is growing worldwide. To meet this demand, some training programs are being expanded, and new ones are being developed. Key to both scenarios is the creation of new course materials. Rather than starting from scratch, however, it's sometimes possible to repurpose materials that already exist. Yet finding suitable materials online can be difficult: They're often widely scattered across the internet or hidden in their home institutions, with no systematic way to find them. This is a common problem for all digital objects. The scientific community has attempted to address this issue by developing a set of rules (which have been called the Findable, Accessible, Interoperable and Reusable [FAIR] principles) to make such objects more findable and reusable. Here, we show how to apply these rules to help make training materials easier to find, (re)use, and adapt, for the benefit of all

ELIXIR and Toxicology: a community in development [version 2; peer review: 2 approved]

Toxicology has been an active research field for many decades, with academic, industrial and government involvement. Modern omics and computational approaches are changing the field, from merely disease-specific observational models into target-specific predictive models. Traditionally, toxicology has strong links with other fields such as biology, chemistry, pharmacology, and medicine. With the rise of synthetic and new engineered materials, alongside ongoing prioritisation needs in chemical risk assessment for existing chemicals, early predictive evaluations are becoming of utmost importance to both scientific and regulatory purposes. ELIXIR is an intergovernmental organisation that brings together life science resources from across Europe. To coordinate the linkage of various life science efforts around modern predictive toxicology, the establishment of a new ELIXIR Community is seen as instrumental. In the past few years, joint efforts, building on incidental overlap, have been piloted in the context of ELIXIR. For example, the EU-ToxRisk, diXa, HeCaToS, transQST, and the nanotoxicology community have worked with the ELIXIR TeSS, Bioschemas, and Compute Platforms and activities. In 2018, a core group of interested parties wrote a proposal, outlining a sketch of what this new ELIXIR Toxicology Community would look like. A recent workshop (held September 30th to October 1st, 2020) extended this into an ELIXIR Toxicology roadmap and a shortlist of limited investment-high gain collaborations to give body to this new community. This Whitepaper outlines the results of these efforts and defines our vision of the ELIXIR Toxicology Community and how it complements other ELIXIR activities

Informatics approaches to understanding TGFβ pathway regulation

In recent years, informatics studies have predicted several new ways in which the transforming growth factor β (TGFβ) signaling pathway can be post-translationally regulated. Subsequently, many of these predictions were experimentally validated. These approaches include phylogenetic predictions for the phosphorylation, sumoylation and ubiquitylation of pathway components, as well as kinetic models of endocytosis, phosphorylation and nucleo-cytoplasmic shuttling. We review these studies and provide a brief `how to' guide for phylogenetics. Our hope is to stimulate experimental tests of informatics-based predictions for TGFβ signaling, as well as for other signaling pathways, and to expand the number of developmental pathways that are being analyzed computationally

Cellular senescence in cancer treatment: friend or foe?

Damage to DNA, the prime target of anticancer therapy, triggers programmed cellular responses. In addition to apoptosis, therapy-mediated premature senescence has been identified as another drug-responsive program that impacts the outcome of cancer therapy. Here, we discuss whether induction of senescence is a beneficial or, rather, a detrimental consequence of the therapeutic intervention