Biological Physics Seminars 2023/2024

Building a new biology: design and construction of synthetic cells

Dr Yuval Elani; Dept. of Chemical Engineering, Imperial College London

Abstract:

Artificial cells are structures that are constructed from the bottom-up using both synthetic and biological components, which resemble biological cells in form and function (Figure below). They are used both as simplified cell models, and as smart microdevices with a range of potential applications in industrial and clinical biotechnology. However, there are a lack of tools available for the construction of artificial cells that allow biomimetic architectures and behaviours to be dialled in a controlled and reproducible fashion. This means that the capabilities of artificial cells cannot match their biological counterparts.

In this talk, I will present some of our efforts to combat this. We have developed a toolkit for the construction of artificial cells of defined size, content, compartmentalisation, and connectivity. These are based on microfluidic, optical tweezer, and novel bio- membrane technologies. We are now moving away from reproducing cellular architectures, and towards mimicking biological behaviours that can be considered the hallmarks of life (sense/response, communication, motility, metabolism, signalling, symbiosis etc.) We are also exploring how artificial cells can be interfaced with the biological cells to form a new class of hybrid living/synthetic organisms (cellular bionics).

Coarse-grained modelling of DNA-RNA hybrids

Eryk Ratajczyk; Turberfield Group, Biophysics & Kavli, University of Oxford

Abstract:

DNA-RNA hybridisation is involved in biological processes such as transcription and DNA replication and is also highly relevant to biotechnological applications including antisense therapy and CRISPR-Cas9 gene editing. By combining existing coarse-grained models for DNA and RNA, we enable the computational study of DNA-RNA hybrid systems on timescales inaccessible to all-atom simulations. We use our model to simulate toehold-mediated strand displacement, finding good agreement with experimental data on sequence-dependent kinetics, and subsequently demonstrate how the base distribution along a strand can be used to modulate displacement kinetics. Finally, we use the model to study R-loops, which reveals a free energy landscape governed by entropic effects. Currently, we are beginning to use the model for simulations of RNA strand invasion in the context of CRISPR-Cas9.