This Dagstuhl Seminar will bring together Computer Scientists, Biologists, Biochemists, and Mathematicians with strong interest, and recent research activities, in the process and outcome of the rational design of RiboNucleic Acids (RNAs). Rational design here is to be understood in its broadest possible definition, and extends beyond the well-studied preferential adoption of a specified (secondary) structure. It particularly includes the design of mutants, multi-stable RNAs, protein-encoding mRNAs, and circuits of interacting RNAs.

Accordingly, design encompasses a variety of computational and experimental tasks that are essential to many areas of molecular biology, system biology, structural biology, synthetic biology, and modern therapeutics. Computationally, design tasks represent a relatively unexplored instance of inverse combinatorial optimization, subject to objective functions that urgently need to capture complex underlying realities.

• To address the future needs and challenges in those areas a fruitful crosstalk between experimentalists, modelers, and providers of computational methods is required. A non-exhaustive list of key questions addressed by the seminar includes:
• Which constructs can be designed for validating/refining functional models and to disentangle errors?
• How to capture complex structural aspects (pseudoknots, kinetics, 3D, interactions...) and how to experimentally validate structural features of designed constructs?
• Can modern techniques in machine learning be used to design RNAs?
• Are the capacities of predictive computational methods sufficient to define suitable objective functions?
• Should rational design be statistical, e.g. to be used as a background model for comparative studies?
• What are the computational and combinatorial properties of design related problems?

The overarching goal of this seminar is to establish a comprehensive repertoire of existing computational methods and to identify novel computational needs to fuel the development of various areas of biology.

In addition to presentations of recent research, the Dagstuhl Seminar will include expository talks presenting existing available methodologies and surveys of key biological questions where design tasks are central. Opportunities will be provided for the discussion of open problems and other topics of shared interest.

Creative Commons BY 3.0 DE

Sven Findeiß, Christoph Flamm, and Yann Ponty