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Teaser, summary, work performed and final results

Periodic Reporting for period 1 - circRTrain (circular RNA Biology Training Network: from biogenesis to biomarkers)

Teaser

CircRTrain focuses on circular RNAs (circRNAs), a new large class of single-stranded RNAs which have only very recently attracted high general interest and become the focus of an increasing number of publications covering diverse fields across basic molecular biology...

Summary

CircRTrain focuses on circular RNAs (circRNAs), a new large class of single-stranded RNAs which have only very recently attracted high general interest and become the focus of an increasing number of publications covering diverse fields across basic molecular biology, neurobiology, neurodegenerative disease, aging, cancer, and biomarker research. The reason for this is twofold. Firstly, circRNAs are unique because of their circular structure and, as a consequence, their unusually high stability. Secondly, only recent breakthroughs in sequencing technology and computational analyses revealed the widespread existence of circRNAs in animal cells, particularly in neural tissues, where circRNA levels are high, dynamic, and similar among different species. Moreover, in aging animal brains the levels of certain circRNAs are strongly elevated, suggesting connections to age-related diseases. Finally, the fact that thousands of different circRNAs can be readily detected in human blood and its components make circRNAs attractive biomarker candidates. The study of circRNAs thus emerges as a novel topic with highest importance for the understanding of such diverse conditions as neurodegenerative diseases, aging, and cancer.
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, who share research interests, but come from different disciplines, such as biochemistry, computational biology, and genetics and thereby tackle scientific research questions from different angles. They are experienced with using different model systems, such as worm, fly, mouse, as well as human samples to apply their respective approaches. The ultimate goal of the project is to establish new medical applications for circRNAs which could be used as potent biomarkers, use circRNAs as stable binders of others RNAs or proteins or exploit the potential of circRNAs to generate stable protein which can be delivered into human cells.
CircRTrain combines these diverse approaches and industrial technologies by training 15 early stage researchers (ESR) at one industry and seven academic partners, which are all leaders in their respective fields. Additionally, cooperation with two R&D companies and one academic partner in the United States extend trainings of the ESRs during exchange visits. ESRs have the opportunity to attend circRNA devoted conferences, and winter- and summer schools which extend their education with expertise in science communication, including science writing, visualization and publishing; intellectual property rights and BioBusiness as well as technical expertise.

Work performed

In order to achieve the ambitious research plan, circRTrain’s first goal was to recruit young researchers to all hosting network partners. After the successful recruitment of 15 early stage researchers via an open and international call, the network was formed and projects were kicked-off during the first network meeting. Within the first 2 years of the project circRTrain researchers performed initial experiments on all objectives of the project:
1. 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.
2. Key experiments have been performed to eliminate but also to deliver circRNAs without affecting the levels of the linear counterpart of the respective circRNA. This was a prerequisite to identify the function of specific circRNAs.
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, first steps have been made validating the potential of circRNAs to generate functional proteins. This will help to explore the function of circRNAs in different pathologies and allow the identification of new medical applications.
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 are now developing 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.

Final results

CircRTrain proposed an ambitious research proposal and is on track with developing the proposed technologies, applying them to different models and defining the role and function of circRNAs. Beyond the scientific impact that circRTrain has on establishing a new research field, it provides a structured network-wide training across countries, sectors and disciplines, which helps to strengthen the connection between research, innovation and education. All fellow projects are situated at the forefront of knowledge of a highly innovative field, so that the ESRs have the opportunity to make important contributions to circRNA research, acquiring scientific achievements from which they can optimally develop a career as an independent researcher. Given their international experience as a prerequisite of the training network, both during their stay at their host institution as well as during secondments, ESRs are equipped with an increased international awareness and competence, and a proven record of adaptability to working in different countries, cultures and working environments. Through their participation in the circRTrain project, ESRs are trained in building their own valuable network of contacts at different levels, with fellow ESRs, supervisors, and other network participants alike, from different sectors and countries. This provides a solid basis for new research collaborations during their future careers, or direct employment opportunities. Ultimately, circRTrain accelerates the formation of highly collaborative a scientific community with focus on circRNA research and high technical expertise and scientific competences.

Website & more info

More info: https://circrtrain.eu/.