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
CircRTrain focuses on circular RNAs (circRNAs), a new large class of single-stranded RNAs which have 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, 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.
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.
In order to achieve the ambitious research plan, excellent early stage researchers have been recruited by circRTrain network partners via an open and international call. Within the project time, circRTrain researchers successfully contributed to the general understanding of all objectives of the project:
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.
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.
CircRTrain proposed an ambitious research proposal including the development of novel 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 provided a structured network-wide training across countries, sectors and disciplines, which helped establishing tight connections between research, innovation and education. All fellow projects have been placed at the forefront of knowledge of a highly innovative field, so that all ESRs had 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 exposure to international scientific environments during their scientific training at their host institution, during secondments as well as during in-person and virtual network trainings, ESRs were 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 were 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 facilitated the establishment of a highly collaborative scientific community with focus on circRNA research and high technical expertise and scientific competences.