£2m study to open doors in synthetic biology

Scientists in Liverpool are leading a new £2m study to open up a new superhighway in synthetic biology.

The four-year project is led by Dr Femi Olorunniji in the School of Pharmacy and Biomolecular Sciences at Liverpool John Moores University and Dr Phoebe Rice at the University of Chicago and funded by the Biotechnology and Biological Sciences Research Council (UK) and National Science Foundation (US).

Together they will develop tools to engineer synthetic cells to carry out specific tasks in the fields of medicine, environmental protection, food production and more.

“Cells are like a car; they have parts we can customise in order to make them perform at different speeds and take different routes,” explained Dr Olorunniji, a research fellow in synthetic biology.

“Cars have some parts which are essential – like the engine – and others you can take out and replace with your own modified parts, like changing the size of the tyres. The project is about testing how we can exert more control by replacing or customising more parts of the cell.”

One of the goals of Synthetic Biology is to design synthetic cells that can be customised for our own use. While this looks and sound exciting, there is a snag. Cells are highly regulated systems because they receive instructions from genes mandating them to carry out prescribed tasks, and they tend to be pretty good at sticking to the scripts.

For example, a pancreatic cell is instructed to produce insulin, a kidney cell detoxifies our system, and so forth. At a simpler level, we can engineer microbes to make interesting products like proteins or enzymes for us. When we succeed in repurposing those microbes to do things for us, they still do so within the context of their in-built control mechanisms, some of which are non-negotiable.

“Given that cells are highly specialised, there is only so much we can coax a bacterial cell to produce more proteins than its system can cope with, or the cells may not like to make our favourite protein because they found the protein to be toxic to their system,” stressed Dr Olorunniji. One way of dealing with the problem is to design ‘synthetic cells’ that are more flexible for us to manipulate.

Applications of synthetic biology could shape medicine, biotechnology and our approach to environmental challenges - Dr Femi Olorunniji

“To continue the car analogy, if we can remove those in-built brakes, we can get the cell motor to run and run and produce as much of our useful protein as we need.”

Using tools called DNA recombinases (enzymes that rearrange DNA in the cell), the UK-US team will engineer, test, rebuild and optimise cells in the laboratory to build a picture of the pathways they need to control.

They will engage with the vast genomic information available online to source hundreds of different segments of DNA and recombinase enzymes to repurpose cells for different uses and will employ recent AI tools to model how the systems behave.

Added Femi: “Synthetic biology is rapidly advancing, and we can see how their applications could shape medicine, biotechnology, and our approach to tackling some environmental challenges, but the better we understand how processes are switched on and switched off in nature (basic science), the better the chance of achieving useful results.

LJMU’s Synthetic Biology Research Group is now recruiting two postdoctoral researchers to the project to work alongside four PhD students already engaged with projects on the DNA recombinase enzymes.

LJMU will receive £850,000 (BBSRC) and University of Chicago £1.25m (NSF) for the duration of the four-year project.

IMAGE: Abdul Alsaleh, Makeba Lawson-Williams, Femi Olorunniji, Cody Hooper-Linegar and Aron Baksh in the Synthetic Biology Lab at LJMU.