‘Complex autoimmune diseases don’t tend to have silver bullets’

13 Jun 2018

Dr Marcus Claesson, lecturer in the School of Microbiology at UCC and principal investigator at APC Microbiome Ireland. Image: SFI

Dr Marcus Claesson of UCC and APC Microbiome Ireland talks about the challenges of finding treatments for digestive autoimmune diseases.

The human body is a complex, natural machine, but the digestive system is on a whole other level when it comes to determining effective treatments for conditions with no apparent one-size-fits-all cure.

However, researchers are working hard to find answers. One of these is Dr Marcus Claesson, a lecturer in the School of Microbiology at the University of Cork (UCC) and a principal investigator at Science Foundation Ireland (SFI) research centre APC Microbiome Ireland.

After finishing his degree in chemical engineering and master’s in bioinformatics at the Chalmers University of Technology in Sweden, he worked as a bioinformatician at AstraZeneca Mölndal and a start-up called AngioGenetics.

After this, he went to UCC to do his PhD to sequence and analyse probiotic Lactobacillus genomes. This was followed by a stint at APC’s spin-out company, Alimentary Health, as well as a longer postdoctoral position in the UCC Eldermet project headed by Prof Paul O’Toole.

In April, he received a total of €504,426 under SFI’s Career Development Award Programme to further his research.

What inspired you to become a researcher?

As a kid, I was an avid Lego builder and reader of all kinds of fact books. Later on, a passion for scuba diving nearly led me to become a marine biologist, but an established researcher swayed me to instead go to engineering school for the better job prospects.

I wasn’t too excited by the local engineering opportunities and jumped ship to an MSc in bioinformatics, which eventually led to a PhD and postdoc research work.

At this stage, I knew I wanted to stay in research, but I only aimed for the academic route halfway into my second postdoc. I haven’t looked back since.

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

In my lab, we are trying to disentangle the role that gut bacteria has in digestive autoimmune diseases. These are primarily the inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis, which involves inflammation of the gastrointestinal tract.

We are working on combining different types of so-called ‘omics’ data from microbial communities called metagenomics with human transcriptomics (active genes), epigenomics (decides which genes become active) and genotypes (inherited genetic variants). When applying machine-learning algorithms on certain combinations of these data, it appears possible to predict future disease outcomes, like how patients respond to medication and when they relapse.

I started talking to Prof Ian Sanderson at the Queen Mary University of London who suggested we apply these methods to his paediatric patients just diagnosed with ulcerative colitis. Many of these children will experience debilitating relapse after six months, which could be prevented with medication if we knew who these were. We will now try to predict this based on microbiota and other ‘omics’ data from intestinal biopsies.

In your opinion, why is your research important?

My research could impact on the quality of lives of many ill children and their families.

The project will also develop the expertise and careers of several young scientists, who also will be able to apply their skillsets on other complex autoimmune diseases.

What commercial applications do you foresee for your research?

The disease burden of ulcerative colitis comes with personal and healthcare costs of up to €29bn in Europe. Positive results could lead to the development of a prognostic tool that predicts treatment outcome, which would be very useful in IBD clinics across the world.

The inner workings of this prognostic tool could also provide better insights into how the disease works, eventually leading to new therapies.

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

These ‘omics’ datasets are very complex and noisy with lots of inter-individual variation, even in separation. Combining these is even more challenging but, luckily, emerging artificial intelligence approaches could help in seeing the forest for the trees.

Are there any common misconceptions about this area of research?

People are naturally looking for simple solutions that will treat or cure them of disease, like changing diet or taking some new herbal remedy. Complex autoimmune diseases don’t tend to have such silver bullets and instead are caused by combinations of known and unknown factors.

The best way to address this is through more interdisciplinary and translational research using large and well-characterised cohorts. Unfortunately, this takes expertise, time and resources.