Professor Susan Rosser: making cells count

And according to Susan, her journey has been more what scientists call a ‘random walk’ than a smooth meteoric trajectory. Her career has taken many an unexpected turn. 

Both of Susan’s parents came from mining families, and she was the first person in her family to have A-levels. Secondary school had its challenges, as she recalls in a stark memory: ‘The windows in the chemistry labs have been bashed in, so we’re sitting there in duffle coats and fingerless gloves.’

But supported by parents who knew university would open untold doors, and surrounded by similarly determined friends, she did get those A-levels – albeit via re-sits after ‘failing spectacularly’ – and arrived on an undergraduate course in Microbiology and Genetics at the University of Dundee.

Again the road was anything but smooth: first she had to retake a failed year (‘I liked to party’), and just as she was getting to grips with studying, she suffered the loss of both her parents to illness within a year; her mum just three weeks before her final exams. 

By that time, Susan’s final-year project had given her a taste for research and, having already decided to study for a PhD, she chose to stay on at Dundee, craving stability and continuity after the loss of her parents. For the next three years she researched the mechanisms of multiple antibiotic resistance.

Today, Susan reflects that it’s PhD students and postdocs, not the heads of labs, who enjoy many of the eureka moments of research, as they’re the ones running the experiments and measuring the results. Looking back to her own PhD days though, she remembers another close encounter with academic disaster. After a year of collecting environmental microbial samples for her research, she returned from a conference trip to discover they’d all been left out of the freezer. A lot of work had to be re-done.

 

Transposon: the jumping gene

But disaster was averted, and by the time Susan became Dr Rosser, she had picked up a travelling companion that stayed with her for the next stage of her scientific life: the transposon, also known as the ‘jumping gene’.

This genetic element was one of the keys to the multiple antibiotic resistance of her PhD research.

‘Transposons jump around the genome picking up antibiotic resistance genes from different genetic contexts. They can also knock genes out if they jump into the sequence that encodes a protein with a function you are interested in – so you can use that. You’ve got a marker in the gene of interest,’ she explains. ‘They can be used as genetic tools as well.’

Her PhD experience led to a post at the University of Cambridge’s Institute of Biotechnology. Her research here, as summarised on her Wikipedia page, might cause a double-take: the biotransformation ‘of cocaine and explosive material’.

She used transposons to try to identify genes encoding the enzymes for metabolising cocaine. These enzymes could act as biosensors for cocaine, useful for catching smugglers or to identify enzymes that can break down cocaine in the event of an overdose. For the explosives project, Susan worked on the insertion of genes into plants that enable them to remove toxins from contaminated soils at former explosives factory sites or in former war zones, a technique that is now being used on military sites in the US.

The next stop was the University of Glasgow, and again Susan’s arrival was far from straightforward. She applied for a post in the Plant Science Department, but says she ‘didn’t have a snowball’s chance …  because I’m not a plant scientist by any stretch of the imagination’. But she put her hat into the ring, partly motivated by the opportunity to visit friends in Glasgow should she land an interview, which she did.

‘I didn't get offered the plant science job, but they liked my interview and gave me a position in biotechnology.’

Ten years of fruitful and reputation-building research followed, during which Susan became Professor Rosser, now focused clearly on engineering biology.

It took a trip many miles west, to Berkeley, California, for a six-month sabbatical, to nudge Susan into moving her research to the east side of Scotland.

She was such a recognised figure in her field that she was asked to sit on the interview panel for the Edinburgh Professorship in Synthetic Biology, and found herself thinking ‘why am I not going for this job?’ She says being out in California gave her the perspective she needed to put in a late application.

That was in 2013 when Susan’s unique professorship spanned two of the University of Edinburgh’s academic schools: the School of Engineering and the School of Biological Sciences.

There quickly followed two major funding awards to build nationally leading facilities serving engineering biology, identified as one of the ‘eight great technologies’ by the UK Government. The first established the Edinburgh Genome Foundry, of which Susan is Co-Director, to build capacity for DNA synthesis and assembly. The second, even larger, award established the UK Centre for Mammalian Synthetic Biology.

Edinburgh has since been firmly recognised as a leader in synthetic biology. Susan says this field does not have a single agreed definition but involves ‘using an engineering approach to build biological systems’. This might mean making cells do something they do not ordinarily do, or making them produce a molecule they do not usually produce, which could range from a therapeutic drug to a fuel molecule to replace fossil fuels.

A large amount of research is dedicated to ‘learning by building’ – synthesising a biological system that replicates what a cell does naturally, to gain a better understanding of that cell’s processes.

For someone who says she set out without clear direction, Susan now has her sights set firmly on one scientific goal. She wants to engineer cells that can deliver a three-stage disease-prevention mechanism. The cells first need to sense a disease state in their host, then crucially they need to be able to ‘compute’ by interpreting multiple inputs, and finally respond by producing a therapeutic to stop the disease from developing.

 

Biology computing

The second step, ‘biology computing’, is where the big challenge lies, and Susan describes it as requiring cells to count and act as switches. For example, a therapeutic response may be needed only if two of three possible biomarkers are present, and the engineered cell needs to be able to sense and respond to that precise combination of inputs.

This is the remit of the ten-year Royal Academy of Engineering Chair in Emerging Technologies that Susan was awarded in 2018: to genetically engineer implantable ‘surveillance cells’ that recognise and process information associated with disease.

And Susan’s work is anchored firmly in real-world demand. She’s working with industry to help deliver new therapeutic products and processes that will benefit patients. One of her team’s most significant collaborations, facilitated with the help of Edinburgh Innovations, is with FUJIFILM Diosynth Biotechnologies (FDB), which supplies pharmaceutical firms with products they use to manufacture major medicines.

Seven of today’s 10 biggest-selling drugs are ‘biologics’, meaning they are based on complex protein molecules, not chemical compounds, and they require cells to manufacture them. Through  Prosperity Partnership funding awarded in 2021, Susan’s team is leading a three-university project with FDB to learn more about the cells that biologics manufacturers rely on and find ways to engineer them to make the manufacture of drugs more efficient and effective. This will speed up clinical trials, and, as Susan says, ‘if you can make drugs cheaper, then it’s cheaper for health providers and the NHS and ultimately available to more patients’.

So what would Mum and Dad think of today’s Professor Susan Rosser and her work at the very edge of human scientific knowledge?

‘I think they would have just been pleased that I got a degree. They didn’t know what was after that, and to be honest I didn’t either.’