Periodic Reporting for period 2 - circRTrain (circular RNA Biology Training Network: from biogenesis to biomarkers)
Période du rapport: 2019-01-01 au 2021-09-30
The overall aims of circRTrain are to:
1. Elucidate the generation and function of circRNAs;
2. Define their role in diseases;
3. Exploit their potential as biomarkers and for medical applications; and
4. Combine cutting-edge technologies and disciplines.
Understanding circRNAs and exploring their medical relevance requires integrating various technologies, such as sequencing, imaging of single molecules as well as whole organisms, elimination and delivery of certain (circular) RNAs, and gene editing. To achieve this circRTrain was formed by a network of investigators, with common interests but from different disciplines, such as biochemistry, computational biology, and genetics. They are experienced with using different model systems, such as worm, fly, mouse, as well as human samples to apply their respective approaches.
CircRTrain combines these diverse approaches and industrial technologies by training 19 early stage researchers (ESR) at one industry and six academic partners and in cooperation with two R&D companies and one academic partner in the United States. The network provided scientific exchange formats at 4 Network Meetings, scientific training in 4 technical skills workshops and complementary training in 5 transferable skill workshops including science writing, visualization and publishing; intellectual property rights and entrepreneurship. The ongoing global COVID 19 pandemic had a major impact on the execution of the secondment plan, one of the mobility components of the network, but scientific exchange and the execution of trainings have always been a high priority for the whole network.
CircRTrain network partners developed, established, and validated technologies for isolating, analysing, expressing and depleting circRNAs while facing a growing need for common experimental standards in this relatively young research field. For this, circRTrain network partners, who are world experts in the circRNA research field, jointly authored a Nature Review article which proposes a set of guidelines for circRNA studies based on the network’s experience. circRTrain network partners believe that the implementation of consensus principles for circRNA research will help move the field forward and allow a better functional understanding of this fascinating group of RNAs.
1. Elucidate the generation and function of circRNAs: By developing computational pipelines for the analysis of circRNAs from RNA sequencing data, network members identified structural requirements for the formation of circRNAs which will help to predict new circRNA species and to identify conserved tissue-specific circRNA regulators. Visualization and localization of circRNA species may contribute to understand their function. CircRTrain developed novel software tools and experimental protocols to visualize single circRNA molecules in the context of the entire macroscopic sample.
2. CircRTrain partners developed and applied a number of tools to manipulate the expression of specific circRNAs independently from their linear counterpart. This led to the identification of regulatory pathways of specific circRNA species during development and disease .
3. Different approaches have been applied to explore the role of circRNAs in neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis, Parkinson’s Disease and Temporal Lobe Epilepsy. The consortium profiled the levels of (specific) circRNAs during the course of the disease, validated their potential as biomarkers in certain diseases, and identified interactors of specific circRNAs in the brain. Additionally, the potential of circRNAs to generate functional proteins has been validated. Through these efforts the importance of specific circRNAs in different pathologies could be explored and new medical applications for specific circRNAs have been identified.
4. Cutting edge technologies, such as new sequencing strategies together with newly developed computational algorithms for data analysis have been necessary to start exploring the function of circRNAs in health and disease state. Network members developed and validated new technologies to observe circRNAs in single cells either by sequencing the transcriptome of single cells or by imaging single circRNA molecules within cells and tissues.