Questions and Answers with Professor of Biochemistry Luke O'Neill

By Clara Caslin

Luke O’Neill is a professor of Biochemistry in the School of Biochemistry and Immunology at Trinity College Dublin. He was educated there where he was awarded an undergraduate degree in Natural Sciences (Biochemistry) in 1985. He completed his postgraduate study at the University of London where he was awarded a PhD in Pharmacology. His research investigates inflammation. For largely unknown reasons it can flare up and cause a range of inflammatory diseases, like Inflammatory Bowel Disease, which remain difficult to treat. I asked him some questions about his studies and the information that he found about Inflammatory Bowel Disease.

Luke O'Neill

What is your title?

Professor of Biochemistry.

How long have you been in your field?

 30 years.

Where did your interest start in it?

In my final undergraduate year in TCD – a project on Crohn’s disease.

What can you tell me about genetics in Crohn’s and Ulcerative Colitis?

Lots of genes have been implicated in inflammatory bowel disease affecting multiple inflammatory pathways. 2 of particular interest to my own research are NOD2 and IRGM. NOD2 is a bacterial sensor, implicating bacteria in disease pathogenesis. IRGM is an inhibitor of an inflammatory pathway involving the NLRP3 inflammasome, which a company I co-founded called Inflazome is developing inhibitors of.

Is there any trends that you have noticed in these diseases?

Both are obviously inflammatory in nature, and most likely involve a disturbance in the gut bacteria. 

Is there anything in your studies that you have noticed leads to shifts of the intestinal bacterial composition in Inflammatory Bowel Disease patients?

No.

Do you think that diet has a lot to do with these diseases? 

Limited evidence of dietary involvement.

What do you think would cause there to be a disrupted immunological response to gut microbiota in genetically susceptible individuals? 

Clearly it is a disease where there is a dysfunction in the how the gut handles bacteria. This then provokes inflammation and the inflammatory process becomes unresolving – a wound that won’t heal.

What causes chronic inflammation in the gut?

Unknown – likely to be a combination of genetics and aberrant handling of gut bacteria, or some yet to be uncovered cause.

What change can be seen when patients are treated with immunosuppressant’s? 

Current therapies show some benefits (eg anti-TNF and mesalamine) but there is a desperate need for new medicines which will limit the inflammatory process locally and promote a healing response.