The splice of life: In conversation with a Nobel laureate

4 Oct 2018

Dr Richard J Roberts and Dr Sally Cudmore. Image: Tomas Tyner/UCC

On a recent visit to APC Microbiome, Dr Sally Cudmore chatted with 1993 Nobel Prize winner Dr Richard J Roberts about what we still have to learn from the microbiome.

Nobel laureate Dr Richard J Roberts loves bacteria. “I find humans too complicated,” he explained. “There is, however, an important connection between humans and bacteria: we couldn’t survive without them.”

Roberts received the 1993 Nobel Prize for his discovery of introns in eukaryotic DNA and the mechanism of gene splicing. His main research interest these days is how bacterial cells control gene expression by using methylation.

Last month, Roberts delivered a talk in University College Cork (UCC) on the ‘Bacterial Methylome’, during which he explained that there is a lot more DNA methylation taking place in bacteria than we have good biological explanations for – so there is probably another big discovery awaiting curious and persistent researchers.

He also spoke to undergraduate students on ‘The Path to the Nobel Prize’ and encouraged students to be curious, follow their interests, take opportunities as they arise and harness their luck. “Do what you love, you will enjoy every day and your career will never feel like a job,” he advised.

‘Every living thing has a microbiome. We tend to focus on humans, which I find are the least interesting of the organisms because they are too complicated’

On his recent visit to APC Microbiome Ireland and the School of Microbiology in UCC, the Science Foundation Ireland research centre’s general manager, Dr Sally Cudmore, caught up with Roberts to ask him about his love of bacteria and a research career that has spanned more than 50 years.

When is the first time you remember being mindful of a microbiome associated with humans, and its importance to our health?

I first became conscious of bacteria living on humans in the period between 1969 and 1972, when I was working with the bacteria Staphylococcus epidermidis and Staphylococcus aureus, which are all over your skin. Around that time, I was also part of a team that worked on bacterial cell wall synthesis. But the consciousness that we have trillions of bacteria living symbiotically in our gastrointestinal tract came along later.

Do you ever personally stop to think about your microbiome, and how life choices (such as diet, exercise, antibiotics etc) might affect it?

No, not really. I don’t think we can do a lot about it as we don’t have the necessary knowledge at the moment to sensibly influence our microbiota. However, I am a vegetarian and would consider myself to have a healthy diet.

Do you have a favourite microbiome fact?

No, but I do have a favourite gut bacterium – Helicobacter pylori – for a number of reasons. It has a number of interesting restriction modification systems (my research area), and is one of a few bacteria that we know for sure can cause cancer.

If you live in the developing world, you almost certainly have a H pylori infection, but you never get asthma. If you live in the developed world, where there is a very low incidence of infection, there is a much higher rate of immune allergic conditions such as asthma, which is a nasty disease. So there is a good correlation.

I knew [the late American microbiologist] Dr Stan Falkow very well, and he believed it was good to have a Helicobacter infection, as Helicobacter has co-evolved with humans. It would be great to develop strains of Helicobacter that can’t cause cancer but are still protective against asthma.

There are other microbiota members that we still don’t know much about, and that is [APC Microbiome Ireland’s] job to figure out.

‘It’s the young people who make the advances, who are willing to take the risks. If you look at Nobel laureates, the majority made their discoveries when they were under 40 years old’

Are there particular directions you believe that microbiome research should go in the next decade?

It is such a broad field. Every living thing has a microbiome. We tend to focus on humans, which I find are the least interesting of the organisms because they are too complicated.

We do now have the tools to start tackling the microbiome, and one of the things I am involved in is a microbiome research institute in Shenzhen in China, which will be named after me. One aspect we will study is the soil microbiome; in particular, the remediation of soil that has been destroyed by industrial activity, as there are large swathes of China where you can’t grow anything.

Microbes do a great job, as do trees. They can take up heavy metals and other contaminants. You could imagine ways in which the microbiomes of trees could absorb heavy metals and persuade the trees to sequester the metals in a useful part of their anatomy. Once mature, these trees could be harvested and the heavy metals extracted.

What research topics will this new microbiome institute focus on?

We will hire young people who are just coming out of a postdoc position, give them five years of support and let them do what they think is interesting.

Usually, new recruits in China tend to be told what to do by senior members, so they don’t have any freedom. We are hoping there will be plenty of Chinese applicants who have been trained abroad and will want to return to China.

It’s the young people who make the advances, who are willing to take the risks. If you look at Nobel laureates in medicine, chemistry or physics, the majority made their discoveries when they were under 40 years old. I was 33 when I discovered splicing.

What are your views on the paucity of women higher up the career ladder? How can we take steps to increase female research leaders?

We should be gender-blind, and just attract and hire good people. But we need to look at how we measure the ‘quality’ of researchers, and measures such as the number of publications or the impact of the journal are not the best systems. If researchers publish good work, why does it matter where? Universities, particularly in Europe, care too much about impact factors and are busy measuring things that bureaucrats monitor.

How can we measure publication quality, as there is no universal measure?

I like an approach where job candidates list their ‘best’ five papers, and indicate their own contributions to that piece of research. Then I read the paper and decide for myself. I don’t care where it was published.

I won’t publish in non-open access journals. Funding agencies have introduced policies to ensure that all research funded by them will be open access from 2020. New open access platforms, such as arXiv, will help to make publicly funded research more accessible.

What advice do you have for microbiome researchers who are starting out on their career?

There are so many aspects to microbiome research. One of my own particular interests would be to find out how the microbiome interacts with the brain. I would love to know what the microbes are saying!

We know that bacteria produce anti-cancer compounds. The way I look at it, bacteria make us their home and they don’t want anything to happen to us, so they go out of their way to protect us against pathogens and against cancer.

Dr Sally Cudmore is the general manager of APC Microbiome Ireland. She previously served as group leader of cell biology at Elan Pharmaceuticals, where she led a gene delivery joint venture with Seattle-based biotech Targeted Genetics. She has a biochemistry degree from UCC, a PhD from the European Molecular Biology Laboratory and an MSc in technology management from University College Dublin.