Bioscience Research Use Cases


Background

To fully exploit the joined-up potential of multiple BMS RIs in a scientific project, the handover must be supported by technical and scientific capabilities: molecular profiling of novel model organisms needs data services for annotation, analysis and archiving; bridging the nano to micro scale for structures and imaging requires adaptation of sample handling and data acquisition pipelines.

Through four distinct access tracks with different pilot projects, WP4 will drive the development of these scientific connectors in partnerships with advanced users. Vetted by a process of cross-RI prioritisation, the access tracks cover all aspects of a bioscience translational pipeline: from novel model organisms to genotype-phenotype predictions. Requirements, feedback and testing by the external partners will drive the development of shared services. The outcome will be a framework for transnational open user access across infrastructures for the sustainable use of the shared services.

The 1st CORBEL Open Call for Research Projects is part of this WP.

Access Track 1: Genotype-to-Phenotype analysis

Predicting disease risk and treatment outcomes for individuals based on ever increasing genomic data is a challenge in biomedicine. Personalized medicine aims to facilitate predictions about phenotypes of individuals (e.g. susceptibility to diseases or therapies). It builds on the analysis of complete genome sequences, functional genomic data, clinical assays and lifestyle parameters. Mathematical Models of genotype-to-phenotype relations are generated by systems biologists to integrate genetic with molecular, physiological and imaging data. These models need to be available to researchers in biomedical areas handling biological samples or in vivo models, large data sets, screens, images and physiological data. Precision biotechnology (white, red, green and blue) will benefit from the same type of model provision.

The aims of Access Track 1 are (i) to provide a set of integrative models with associated data and technologies for life scientists to relate genotype to phenotype and (ii) to establish a pipeline for users to produce such integrative models.

The objective is to establish corresponding research (i) and service (ii) pipelines between RIs. The integration of the RIs will be implemented by research projects that aim to predict specific aspects of phenotypes from individual information. The pipelines will empower users to address main research topics, such as systems and personalized medicine, rare diseases, metabolic and inflammatory diseases, cancer, precision biotechnology and modern non-recombinant agriculture. There will be imminent impact for translational research and the health and biotechnology industry.

Example of an ongoing pilot project:
Terminate-NB: From Cancer DiagnOMICS to Precision Medicine: Model Neuroblastoma 

Access Track 2: Predictive systems pharmacology for safer drugs and chemical products

Chemical compounds are omnipresent in our daily lives as natural or synthetic products, be they drugs to treat diseases, pesticides to protect crops, food additives, and many more. Understanding how these chemicals affect biological processes is fundamental to a knowledge-based management of the needs and risks of the world´s growing population. It embraces all aspects of life such as human health and well-being, aging, nutrition and environment.

The aim of this Access Track is to build a seamless workflow with the experimental and virtual services of BMS RIs and complementary RIs that contribute to the quantitative analysis, description, comprehension and modelling of the effects of chemical substances on biological systems (pharmacology). A broad variety of major research topics in the field of health, food and environment that are in line with EU-funding strategy to solve societal challenges can be addressed. This includes most obviously the field of medical drug research (target validation, drug repurposing strategies, synergistic drug combinations and drug adverse effects, toxicology, safety, reduction of attrition rates, biomarker discovery), but extends seamlessly to the impacts of chemicals on veterinary, agricultural and environmental applications exploiting target structure similarities.

There is a significant cross-talk to the other access tracks as well as to the use cases in the medical sciences; the participating RIs will ensure a tight alignment with this pharmacology workflow.

Example of an ongoing pilot project:
Cystic Fibrosis

Access Track 3: Structure-function analysis of large protein complexes

Understanding how the structure of protein complexes and organelles gives rise to their function is a central challenge to comprehend the molecular mechanisms of health and disease. Such information is also fundamental to rational therapy design: knowledge of the atomic and molecular structure of life’s machinery allows predicting its function and interfering with it. Clearly, this process requires an integrated approach combining high-resolution structure determination of isolated protein complexes with validation of the structure, interactions and, ultimately, their functions in a physiological context in situ. Only by directly combining in vitro and in situ imaging methods can structure be determined in its functional context and the predicted function be validated.

The main research topics that will be supported are in line with the EU funding strategy, including systems medicine, disease mechanisms etc. Moreover, there is imminent impact for pharmaceutical applications and drug design, as well as imaging technology innovation and image data sharing through the development of new standards.

Example of an ongoing pilot project:
Visualising picorna entry in the context of a novel viral entry pathway

Access Track 4: Marine Metazoan Developmental Models

Advances in the understanding of many fundamental biological processes are hampered by their inaccessibility to experimentation in traditional animal model species, ethical considerations concerning research on vertebrates and particularly mammals, and incomplete linkage to data analysis pipelines, data integration and predictive models. The advent of high-volume low-cost ‘omics approaches, along with major improvements in imaging and functional genomics technologies, and a vast increase in computer power, has opened a potential goldmine of novel animal models covering the vast range of marine biodiversity across all the animal phyla.

With this access track, we aim for a complementary set of selected marine metazoan models for developmental and cell biology:
1) Set up integrated databases combining sequence and imaging data via pipelines linking EMBRC-ERIC, Euro-BioImaging, EMBL-ELIXIR and ISBE as user-friendly entry portals for both established and new users. These would be designed to allow integration with computational models of development, and future integration also of gene manipulation phenotypes and chemical response data.
2) Provide access to biological material as well as functional genomics and imaging capabilities for testing and exploitation of these models in selected pilot user test cases.

This Access Track is geared to provide advanced understanding of biological mechanisms underlying disease, through promoting the use of diverse and experimentally accessible alternative model species. Marine species have long proved powerful models for understanding many cellular phenomena including the gene regulatory networks underlying cellular and developmental transitions, fertilisation, cell division, differentiation, stem cell biology, morphogenesis, regeneration, ageing and physiological responses. Promotion of invertebrate marine models empowered with computational analysis and predictions will make a significant impact on reducing the use of vertebrates and in particular mammals in biomedical research.

Example of an ongoing pilot project:
Developing Clytia as a neurobiology research model

This project receives funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654248.