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Aurelia Chaise's picture

Developing a green economy is a top European priority. This creates an urgent need to train European researchers in the fields of synthetic biology and bio-analytics, focusing particularly on the ability to solve complex challenges in the design of relevant proteins.

 

The Marie Skłodowska-Curie Innovative Training Network “RNAct - Enabling proteins with RNA recognition motifs for synthetic biology and bio-analyticsaddresses this need by creating a comprehensive and cross-disciplinary consortium of 10 Early Stage Researchers (ESRs) at the forefront of their research. The RNAct project’s main goal is to post-transcriptionally regulate gene expression and to detect specific RNAs by designing and characterising proteins containing RNA Recognition Motifs (RRM), which are regions that recognise these biomolecules.

 

The consortium

RNAct brings together seven beneficiary institutions from five different European countries. Four academic organizations (VUB, CNRS, CSIC, and HMGU) and three companies (Giotto Biotech, Dynamic Biosensors and Ridgeview Instruments AB) join forces with the support of six partner universities (University of Liège, Lorraine University, Technical University of Munich, University of Florence, Polytechnic University of Valencia and Uppsala University) to build up a highly interdisciplinary network to tackle the ambitious goals of the project.

 

The computational/experimental binomial

The project promotes and integrates interactions between the computational and experimental fields as well as academic and industrial settings. ESRs 1-5 are developing computational methods whereas ESRs 6-10 are working on in vitro and in-cell experiments. All the data and results obtained from both sides are integrated in a central database, favouring the cross-fertilisation of wet and dry disciplines. On one hand, computational and experimental ESRs will be paired with each other to gain interdisciplinary insights through buddy visits; on the other hand, secondments will allow the fellows to be exposed to innovation both in academy and industry.

 

The work packages

The RNAct research is organised in three connected scientific work packages to accomplish the main goals of the project:

 

Work package 1 aims to design and characterise RRMs. The ESRs will work with proteins containing one RRM and proteins containing several of these domains.

 

Work package 2 aims to represent and design dynamic proteins. Since dynamic regions of proteins adopt different conformations, obtaining accurate in silico structural models from experimental data is a difficult challenge. Here the ESRs will integrate experimental data in computational approaches at the protein sequence, structure and interaction levels, and will study how these data can be actively used for protein design.

 

Work package 3 is focused on the bio-analytics and synthetic biology fields. The ESRs will test the designed RRMs in cells and will incorporate them in biosensors to detect specific RNAs. All the results generated in this part will be useful to keep improving the RRM design cycle.

 

The design cycle in a nutshell

The three work packages are connected in a yearly design cycle. This ‘RRM design cycle’ starts with computational approaches at the sequence and structure levels of proteins and RNA. In this way, we identify positions and mutations along the proteins and check how they might affect the RNA binding. After an experimental validation with high-throughput methods, the best performing RRMs will be further investigated at the atomic level with structural biology approaches and will be applied in (i) synthetic biology (e.g., incorporate an RRM in  bacteria to enable post-translational regulation) and in (ii) bio-analytics (e.g., incorporate the selected RRMs in disruptive technologies such as switchSENSEⓇ and LigandTraceⓇ to detect specific RNAs in vitro and in vivo, respectively).

RNAct introduces new elements in existing computational approaches to enable the incorporation of protein dynamics and RNA interactions in protein design, and connects this new computational methodology via a tight feedback loop with experimental approaches at the molecular and cell levels.

 

Current status

All the ESRs have started working on their respective projects and InteR3M, the first version of the database, is already up and running. It includes all the available information about RRM and RNA binding, and all the ESRs will provide new data from their computational or experimental assays to keep improving it.

 

The RNAct ESRs are now reaching their scientific cruising speed and are ready for the challenges ahead by collaboratively looking for the best solutions and innovations in both the synthetic biology and bio-analytics fields.

 

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Written by:

Anna Pérez-Ràfols (Giotto Biotech, rafols@giottobiotech.com);

Joel Roca-Martínez (VUB, joel.roca.martinez@vub.be

 

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