Team:Heidelberg/Description
The Legend of Cellda
Project Overview
The Legend of Cellda - A link between proteins
Abstract
After decades of work, synthetic biologists have gathered a vast repertoire of biological standard parts to manipulate organisms. Usually, this manipulation is exerted through the regulation of DNA and its expression, but there are many other cellular gateways that may be just as suited to exert control on, yet remain widely unexplored. A lost opportunity! This year we, the iGEM Team Heidelberg 2020, aimed to develop tools that would extend the capabilities of biological manipulation to more domains than just the control of DNA, but to harness the power of RNA and RNA-binding proteins to create new tools with which cellular systems could be controlled.We created design principles for the construction of RNA-linked fusion proteins and designed an assay to assess the association strength of RNA-linked fusion proteins. Further we explored PPR and Pumilio Homology domains and designed assays to test them for their suitability as RNA control elements. In support of our assays and proposed implementation applications containing RNA binding proteins we created PRISM, a language model trained on 500.000 protein sequences and their corresponding annotations, fine-tuned on RNA-binding protein sequences, their annotations and their related RNA-motif. Upon user input of the annotations and/ or a RNA-motif the corresponding sequence is generated. Further, with 3DOC we provide a tool, which is capable of generating 3D structures of concatenated protein domains and fusion proteins.
But when designing new tools for cellular regulation, we did not stick blatantly to proteins. With designs of RNA Triple-Helices we tried mimicking dCas-Transcriptionfactor complexes. With our redesign of the famous Tetrahymena Trans-splicing Ribozyme, we present a modular tool that allows RNA based RNA translation control. To support the structural design of our RNA constructs we created CoNCoRDe. The scripts provided include scripts for classical RNA design as well as a reinforcement-learning environment for RNA design. We also provide a RNA Combinatorics Model.
In times of Corona science communication is a daunting and an encouraging experience at the same time. For us, it was important to bring up an educational concept with a long-lasting effect. This is why we created our experiment booklet about synthetic biology for schools and extracurricular courses. With our digital science slam we were able to reach out to people across society. Last but not least we built RISE for the iGEM community. RISE is our universal search engine for the iGEM Registry, which enables users to filter and search for documentation and parts.
An introduction to our project is also given in our project promotion video:
You can see a more comprehensive explanation of our project in our presentation video: