Construction of a protocell capable of in-situ RNA computation

Motivation

Understanding and engineering living cells, a basic unit of life, is one of the biggest goals in biology. However, even modelling of simple cells like E. coli is a challenging task due to its complexity. A simpler synthetic alternative to real cells – protocells – can therefore be built to design systems with cell-like traits. Protocells can provide us with insight on the principles of biology, and could, in the long run, be used in biomedical applications such as drug delivery and biosensing. Among available biomaterials, RNA molecules can be programmed to perform various molecular computing including logic gates and neural networks. Indeed, RNA molecules are an important part of the regulatory network of living cells, with a significant portion of RNAs being non-coding RNAs.

The project

In this project, you will have the exciting opportunity to build a protocell system bearing rationally designed RNA reaction circuits. State-of-the-art in-situ RNA circuits based on our recent work (Bae et al., 2021, Nano Lett.) will be used to build RNA reaction circuits inside protocells that mimic genetic networks of living cells. Specifically, you will encapsulate RNA transcription machinery consisting of T7 RNA polymerase, DNA templates and ribonucleotides inside of a giant unilamellar vesicle with ~5 μm diameter. The water-in-oil emulsion method will be used for high-efficiency encapsulation of the transcription machinery. The operation of the RNA circuits will be monitored by an external probe or a light-up RNA aptamer system such as Broccoli. The project also involves a significant amount of computational work as you will be rationally designing the interaction between different RNA species using a set of designing rules to implement circuits for logic gates, signal amplification and sensing of biomolecules.

We are looking for an enthusiastic, self-motivated student to work on this exciting project. The ideal candidate will have experience in wet-lab experiments, good communication skills in English and most importantly, a determined mindset to pursue the research project. We are particularly interested in candidates with previous experience in nucleic acids nanotechnology, membrane biophysics and/or synthetic biology.

Applicants are expected to hold a first or upper-second class degree in a relevant discipline (or equivalent overseas qualification), or a lower second plus a good masters degree (distinction normally required).

English Language requirements 

International applicants may also require an IELTS (English-language test) score of 6.5 or above (or equivalent) with 6.0 in each individual category.

The project will be supervised by Dr Wooli Bae and Prof. André Gerber at the University of Surrey. Wooli Bae is a lecturer at the Department of Physics with the research area of nucleic acid nanotechnology and synthetic biology. André Gerber is Professor of RNA Biology at the School of Bioscience and Medicine with a research interest in post-transcriptional gene regulation mediated by RNA-binding proteins and non-coding RNAs.