Designing RNA Logic Assemblies for Transcriptional RNA regulators

The innovation of logical RNA structures in synthetic biology aims to forge programmable RNA assemblies capable of executing complex computational operations within biological systems. The ambition is to design logic operations rooted in RNA assemblies, facilitating multiple inputs.

RNAs based regulators include with the toehold switch: Soon after, the introduction of straightforward logic with multiple inputs further advanced the concept, leading to significant advances in RNA regulation based devices-.

Recent advancements in RNA-based logic systems have expanded to incorporate transcriptional activators like STAR elements. In contrast to toehold switches, which operate based on the availability of the ribosome binding site (RBS), STAR elements act by removing an entire RNA terminator, typically a hairpin structure.

The idea of this project is to explore assembly designs using computational methods to determine specific input and output sequences for any given logic table. Natural transcriptional regulators often exhibit complex structures, such as repC and RNAII, in contrast to the more straightforward synthetic constructs like STAR elements.

Goals

The project aims to explore and potentially compare multiple methodologies:

  • Using genetic search/optimisation informed by thermodynamic predictions and NUPACK's computational tools.
  • Constructing regulators based on existing models, akin to ribocomputing devices.
  • Investigating natural RNA transcriptional regulation mechanisms through genomic analysis to derive general construction rules for RNA regulators, with the support of deep learning for improved design precision and innovation.

The ideal candidate for this project would have a keen interest in both computational biology and experimental laboratory work, with a stronger emphasis on the computational aspect due to the project's intricate nature.

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  7. Duo Ma, Yuexin Li, Kaiyue Wu, Zhaoqing Yan, Anli A. Tang, Soma Chaudhary, Zachary M. Ticktin, Jonathan Alcantar-Fernandez, Jos ́e L. Moreno-Camacho, Abraham Campos-Romero, and Alexander A. Green. Multi-arm RNA junctions encoding molecular logic unconstrained by input sequence for versatile cell-free diagnostics. Nature Biomedical Engineering, 6(3):298–309, March 2022.
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Additional Information

Project Capacity One IREP student
Project available for Spring, Summer and Fall 2024
Credits 18
Available via Remote No
Project Supervisor Jérémie Marlhens