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I joined Ingenza in 2009 as a graduate in biomedical sciences. Five years later, with some industrial experience behind me, I decided that I would like to do a PhD, ideally while continuing to work at Ingenza. However, although there are a number of opportunities to study for a PhD and gain some industrial experience, there aren’t many that are fully industrially focused. That led me to apply for an 1851 Royal Commission Fellowship, a scheme that funds innovative doctoral research with commercial potential.
What really attracted me to this scheme was that I could continue my work at Ingenza, trying to solve some of the challenges facing biotech companies, and submit the results of my research to the University of Edinburgh to obtain my PhD. We put together a proposal focused on speeding up the manufacture of fuels, chemicals and new pharmaceuticals by improving and accelerating the way microbial strains are engineered and, in 2014, I was awarded an Industrial Fellowship – a first for Ingenza.
in 2014, I was awarded an Industrial Fellowship – a first for Ingenza.
Despite the promise of synthetic biology, the engineering of microbes is not yet predictable. As a result, you need to cast your net wide and work on a large scale to be successful. Rather than making two or three constructs, you want to make 50 to 100 constructs, and test them all to see what works – and learn from what doesn’t – which then drives the next round of optimisation.
The more constructs you can test at one time the better, and automation is an obvious way forward. At that time, our inABLE® technology – which allows very rapid DNA assembly – was still largely a manual process, and so I looked at each step of the process to see where liquid handling technologies could be introduced.
This patent-pending process is now being used throughout Ingenza and is accelerating the engineering of microbes for a number of industrial bioprocesses.
One of the biggest obstacles to automation was that the purification step involved running the DNA on a gel, visualising it and then isolating the required fragment from the gel, which could only be done manually. To overcome this issue, I developed a novel purification technology that could be automated. This approach uses phosphorothioate bonds to protect the DNA of interest from exonuclease attack in vitro. The unprotected DNA fragments are then degraded, and a quick spin column-based clean-up is all that is required to generate assembly-ready DNA. This patent-pending process is now being used throughout Ingenza and is accelerating the engineering of microbes for a number of industrial bioprocesses.
Alongside this research, I also collaborated with the School of Chemistry at the University of Edinburgh, which has a world-class mass spectrometry facility with expertise in protein characterisation. This gave me the opportunity to use high tech mass spec systems to analyse the engineered microbes at the proteome level – rather than looking at one specific protein in great detail – to see how they had been affected and guide the next stage of my research.
For me, the exciting thing about achieving my PhD through an 1851 Fellowship was that my research was industry led – focusing on the challenges facing biotech companies – and I remained a member of the Ingenza staff. At the same time, the university provided the academic and mass spec support I needed, and benefitted from an industrial collaboration. It’s a win-win situation.