How a study on ‘bubble boy’ syndrome sparked a career in gene editing

8 Apr 2020

Dr Ciaran Lee, APC Microbiome Ireland/UCC. Image: Tomas Tyner/UCC

Dr Ciaran Lee of APC Microbiome Ireland and UCC is using CRISPR to better understand the mysterious interaction between bacteria and our gut.

After completing his undergraduate degree at University College Cork (UCC), Dr Ciaran Lee undertook a PhD to develop gene-editing techniques to correct mutations causing cystic fibrosis.

He later obtained a postdoctoral fellowship from the Cystinosis Research Foundation to investigate the use of gene editing in the rare disease cystinosis. Lee then travelled to the US as a postdoc to the Georgia Institute of Technology to develop gene-editing systems to treat sickle-cell disease, and followed this to become director of the Genome Editing Core at Rice University.

After six years in the US, Lee moved to the SFI centre APC Microbiome Ireland to investigate the role of the immune system in gut inflammation and colorectal cancer.

What inspired you to become a researcher?

Growing up, I was always a curious child and developed a strong sense of critical thinking from conversations with my father. My interest in genetics and DNA then began by watching detective shows with a heavy focus on forensics.

Still, it wasn’t until the final year of my undergraduate degree at UCC when I read a research paper describing the use of zinc finger nucleases (ZFNs) to correct a gene defect which causes ‘bubble boy’ syndrome that the spark was ignited.

I found the concept of being able to edit the genetic code of life fascinating and, within a year of reading the paper, I started a PhD working on designing ZFNs to target mutations causing cystic fibrosis. Starting my PhD was a steep learning curve but the freedom to dream up a project and see it through got me hooked on academic research.

Can you tell us about the research you’re currently working on?

Currently my research is focused on understanding the interaction between the bacteria in our gut and our immune system, and how commensal species of bacteria elicit anti-inflammatory responses. My work uses the exciting new gene editing tool CRISPR, which provides the shaky plot device in the Hollywood blockbuster Rampage and is the focus of the Netflix documentary Unnatural Selection.

The ultimate goal of the research is to understand how commensal bacteria in the gut communicate with the host organism and identify mechanisms and targets for engineering immune cells.

My time is split between the labs of Prof Douwe van Sinderen and Dr Ken Nally and builds on their work describing the effects of the commensal bacteria Bifidobacterium breve on the host immune system.

In your opinion, why is your research important?

Inflammatory diseases and autoimmune disorders are on the rise, particularly in developed nations. This has been linked to changes in lifestyle, including diet, which affect the composition of microbes in the gut.

A deeper understanding of the interaction between microbes and the immune system in our gut and how specific strains of bacteria can induce immune tolerance will lead to novel therapies for inflammatory diseases.

What commercial applications do you foresee for your research?

The knowledge gained from studying host-microbe interactions will open up opportunities for new drug therapies and novel live biotherapeutics for treating inflammatory diseases.

What are some of the biggest challenges you face as a researcher in your field?

While academic research gives the freedom to pursue any avenue of research, obtaining funding to support your work is an ongoing challenge. Preparing grant applications is very time consuming and success rates are quite low due to competition for limited funding.

This can be frustrating and perseverance is essential. Having recently become a father, I am learning that achieving a good work-life balance with a young family is a constant challenge given the pace at which the research field is moving.

Are there any common misconceptions about this area of research?

There are many health claims about the effects of probiotic bacteria based on correlative studies without definitive underlying mechanisms or causative studies. This has the unfortunate effect of creating hype in the media surrounding potential health benefits.

To help address these misconceptions, it is important for scientists to choose our words carefully when presenting our work to the public and to our peers. APC Microbiome Ireland has an excellent public engagement and education programme which aims to increase the public’s understanding of the gut microbiome.

What are some of the areas of research you’d like to see tackled in the years ahead?

I would like to see strong mechanistic studies defining the role our gut microbes play in influencing how our immune systems function during inflammatory bowel disease and cancer.

Outside my current field of study, I would like to see the clinical translation of personalised gene editing-based therapies with innovative pricing strategies to make these widely available, and improvements in renewable energy systems.

Are you a researcher with an interesting project to share? Let us know by emailing with the subject line ‘Science Uncovered’.