John O’Brien
This profile was originally published as part of the MRC Annual Review 06/07: People behind discovery. The review tells the stories of just a handful of MRC scientists, the work they do and the career paths they have chosen.
Research support scientist at the MRC Laboratory of Molecular Biology (LMB), Cambridge.
John O’Brien is an MRC scientist who has spent much of the past few years modifying a gene gun for use in neurodegeneration research. He is currently studying for a PhD by publication.
“When I left school after my A levels, my parents didn’t have the money to send me to university. I was offered a job at Lloyds Bank but turned it down because you have to wear a suit every day. The next day I went to an open day at the Babraham Institute and managed to climb onto the bottom rung of the ladder as a lab assistant.
I knew little about science, but the job taught me the bench skills I would eventually need to work on my own. I went to college one day a week to study for my Higher National Certificate in microbiology and biochemistry. I was studying from eight in the morning until after 10 at night and then back in the lab early the next morning. Then I approached Sir Barry Cross, the Director of the institute, about doing a biochemistry Honours degree on day release. I was the first person to be allowed to do this.
A move to the LMB
In 1996, I met Steve Hunt, then a neurobiology group leader at the Laboratory of Molecular Biology (LMB). Even though my background was cell biology and I had little knowledge of the brain, he took me on because of the skills I’d learnt at Babraham. Two years later I began to study how the gene gun could be adapted to inject DNA into brain cells rather than chloroplasts — the powerhouses of plant cells.
With brain cells, it was like shooting a clay pigeon with a 12-bore shotgun — it wasted ammunition and damaged the surrounding tissue. My job for the next ten years was to improve the gun’s accuracy. To do this I developed a special barrel to reduce the gas pressure and target area. My eureka moment came over coffee with a retired police firearms expert who explained to me how the barrel of a gun works.
In 2006 I fulfilled a major ambition in giving one of a series of annual talks to the whole of LMB. I’m still working on being a first author on a Nature paper.
Sights on a PhD
I’m one of the few people to become a fellow of the Society of Biology without a PhD, and this led to the idea of me doing a PhD by published work. This offers an alternative route to getting a PhD people with a body of work in a specific area — in my case the gene gun. The LMB is supporting me through this and I’m reaching the end of the process now and should have my viva in a few months.
It’s been satisfying writing up the work of the past 12 years of my life. I’m proud of what I’ve achieved but I know I was lucky to have been given the opportunity to explore the gene gun work in the first place. The PhD is the icing on the cake - the LMB see me as a professional anyway but gaining the ‘Dr’ and losing the ‘Mr’ will help me to show those outside the LMB that I am working at a professional level.
Looking for answers
In recent years I’ve been able to refine the use of gold particles as ‘bullets’ to deliver DNA into cells. Originally they were far too large and damaged the cells, but I’ve managed to use gold nanoparticles. That means we can start using these smaller particles to investigate neurodegenerative diseases — I can finally start using the gene gun and a technique I’ve developed for cutting and keeping mature brain tissue alive to start answering scientific questions.
In 2007 I set up my own business called Modolistics manufacturing the modified gene barrel for use with the off-the-shelf gene gun. I also spend a lot of time providing advice to researchers on how to use the gun, as well as starting to collaborate with researchers from other research institutes, using the gene gun to inject DNA into other cells. I feel really lucky. Throughout my career so much has depended on people giving me a chance. But I’ve also found out that you’ve got to keep at it. If you’re naturally inquisitive and want to learn, science is unique. It’s not a routine job, every day is different. And if you’re prepared to listen and learn and respect your scientist elders, it’s the best job in the world.”
Updated February 2012