Meet the Community – Michael Booth

Michael Booth was determined to find his way in synthetic biology and synthetic cell research. After a PhD in nucleic acid chemistry* at Cambridge, during which Michael invented new DNA sequencing techniques, he took a career turn and joined Professor Hagan Bayley’s group at Oxford. There, he used his knowledge of nucleic acid chemistry to try to make synthetic cells from droplets. Michael Booth is now a Royal Society University Research Fellow and leads his own research group at University College London.

He tells us more about his team’s expertise, his collaborations, and the innovations that could be developed through synthetic cell research.

What is your definition of a synthetic cell?

There is a lot of conversation about this, but I think everyone has a reasonably similar definition, that is a compartment with at least some minimal cell-like functionality. But what changes from person to person are the applications and the direction of research. Many people are trying to build synthetic cells that recapitulate as closely as possible the functionality of living cells. However, my motivation is rather to take advantage of synthetic cells for interesting applications, such as the development of smart medicines or the development of biotechnologies to study specific pathways in cells.

What is the specialty of your team?

The main focus of our research is to use chemistry to develop methods to remotely control the function of nucleic acids*. One of the applications we are exploring is to use these nucleic acids to control the functions of synthetic cells, such as their interactions with living cells. We are focusing on remote stimuli, such as light, temperature and magnetism, as these allow precise, non-invasive activation with the potential for future in vivo application.

What promises can synthetic cells offer our society?

I expect there will be a niche for them in many different areas, including as therapeutics. Synthetic cells are interesting because they sit in an intermediate position. They are not living cells, so they won’t have the drawbacks of cell-based therapies; but they still have much more functionality than single molecules. Furthermore, like single molecules, they can easily incorporate synthetic components, which living cells cannot.

With our added ability to remotely control their function, synthetic cells might be applied to synthesize in situ a signaling molecule or therapeutic, especially something you can’t normally store, in any location you choose.

The European Synthetic Cell initiative aims to bridge the gap between research and technology to deliver smart, green innovations based on synthetic cell research. What are the main requirements for you to achieve this?

We need more conversations and collaborations with researchers and more conversations with industry, but above all more research. And research funding!

You mentioned the need to collaborate. Can you give us a few examples of your current collaborations?

* Nucleic acids are long chain of molecules made out of units called nucleotides. The two main classes of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). More info

I’m collaborating with Matthew Baker and Shelley Wickham who are based in Australia. We have a grant on novel mechanisms of synthetic cell communication and control. Matthew is a biophysicist, working on protein function, droplets, and microscopy, while Shelley is an expert in DNA nanotechnology. I was also recently involved in an article published in the Journal of American Chemical Society from the lab of Lorenzo di Michele, from the University of Cambridge, in which we combined my experience of cell-free expression** with his recent development of DNA-based compartments.

** The cell-free gene expression approach involves reproducing in vitro cellular processes such as transcription, copying a DNA segment into a new messenger RNA (mRNA) molecule, and translation, decoding the mRNA to synthesize proteins.

Thank you Michael for answering our questions!  Who would you like to hear from next in our community? Let us know!

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