The Marie Skłodowska-Curie Actions Doctoral Network nEXt-RNA (next generation scientists studying extracellular RNA) brings together 7 beneficiaries with 11 PhD students and 8 associated partners from the academic and non-academic sector. The network is designed to to combine excellent research projects with inter-disciplinary and inter-sectoral collaborations, student exchange and network-wide training programmes to educate the next-generation of research leaders in the field of exRNA.

To address most outstanding questions and knowledge gaps in the exRNA field, nEXt-RNA research will follow a systems approach to investigate the mechanisms of cross-kingdom exRNA communication at the molecular, cellular, and organismal levels accross diverse host-pathogen interactions, comparing viral, microbial, plant, animal and human systems. Gaining a fundamental understanding of exRNA mechanisms and modes-of-action will allow to develop innovative solutions for pathogen control.

The overall goals of nEXt-RNA:

• Conduct excellent research projects hosted by top-ranked European universities and supervised by expert PIs, working together to address key knowledge gaps in exRNA biology.
• Educate and supervise DCs in inter-disciplinary and intersectoral exRNA research and innovations through implemented secondments and training visits at academic and non-academic institutions.
• Provide a network-wide training programme to educate and train DCs in scientific technologies, transferable skills, and entrepreneurship through dedicated workshops and training courses.
• Broaden scientific networking of European exRNA researchers and innovators.
• Foster an environment for exchanging new ideas and knowledge to boost exRNA applications and innovation in Europe.

The nEXt-RNA research and training programme

The next-RNA research projects are interconnected and embedded into 3 scientific work packages (WPs) addressing fundamental research questions of exRNA functions. Together they aim to fill conceptual gaps in exRNA biology and, by sharing exRNA technologies, to create unique synergies and promote exRNA research, innovation, and education.

WP1: Mechanisms of cross-kingdom exRNA transmission, lead: ENS UDUS, DC1 : mRNA transmission from Ustilago into maize UoC, DC2: Small RNA transmission upon viral/viroid infections in plants ENS, DC3: Small RNA transmission from plants and humans into Pseudomonas spp. UEDIN, DC4: Small RNA transmission from parasitic nematodes into mouse ↓ Develop novel tools to track and visualize RNA transmission Identify exRNA functional interaction partners relevant for the transmission Explore functional roles and modes-of action of exRNAs in target cells

WP2: Mechanisms of exRNA uptake and delivery, lead: UHAM UHAM, DC5: Uptake of fungal EVs into plant cells UEDIN, DC6: Uptake of EVs and non-vesicular exRNA into mouse cells UU, DC7: Correlating EV fusion and RNA delivery in human cells ↓ Advance understanding on EV attachment, uptake and delivery of exRNA Explore uptake of exRNA transported by different carriers Correlate EV fusion and endosomal escape with RNA delivery

WP3: exRNA application and innovations, lead: UNIPA UNIPA, DC8 : Exploit citrus-derived nanovesicles for RNA delivery into  mammals UHAM, DC9: Exploit microalgae-derived EVs for RNA delivery into fungi UDUS, DC10: VLP-based mRNA delivery into human and plants ENS, DC11: Engineer exAGOs for small RNA delivery through VLPs ↓ Translate gained knowledge in WP1 and WP2 into synthetic exRNA approaches Collaboration between academics with university spin-off and start-ups Develop plant-derived nano-scale technologies for RNA in diverse target organisms

Partner universities: University of Düsseldorf (UDUS), University of Crete (UoC), University of Paris (ENS), University of Edinburgh (UEDIN), University of Hamburg (UHAM), Utrecht University (UU), University of Palermo (UNIPA).

Inter-disciplinary and intersectoral student exchange through secondments and network-wide training programmes will offer all DCs a unique perspective to develop skills and creativity needed for their future career development.

Training modules include:

• Workshop on RNA in vivo visualisation techniques
• Hands-on exRNA bioinformatics course
• Entrepreneur boot camp
• Workshop on exRNA applications
• Project and data management
• Science communication skills
• Workshop on EU funding opportunities and grant writing skills