How a TB expert found a potential cause of Parkinson’s disease

25 May 2018

 Mx Gutierrez

By studying the mechanism our immune cells use to clear bacterial infections, Crick group leader and tuberculosis (TB) expert, Max Gutierrez, has uncovered a potential cause of Parkinson's disease - something that has evaded Parkinson's specialists for decades. The study, published in The EMBO Journal this week, highlights the valuable contributions that field 'outsiders' can make in the pursuit of discovery science. Max tells us what it's like to be a TB researcher pushing the boundaries of Parkinson's research.  

When I started investigating the role of LRRK2 in the immune system, I had no idea that I was embarking on a project that would shed light on Parkinson's disease.

The connection between these seemingly disparate fields is that mutations in LRRK2 are the most common genetic cause of Parkinson's disease. So, while cell biologists like me are studying the role of this protein in the immune system, neuroscientists are trying to work out whether LRRK2 causes neurons to degenerate and, if so, how they can stop it.

It was actually a neuroscientist colleague of mine, Patrick Lewis, who convinced me that we should look at the connection between these two diseases. As a neurodegenerative disease expert, he was my guide in the Parkinson's field. His knowledge of LRRK2 was critical for many important decisions that we made during this five year-long project.

Coming to the subject as an outsider, I obviously had a lot of catching up to do. But I was pleasantly surprised at how many novel links emerged between the two fields - influencing the way that we approached our respective research questions.

I still remember a time when I was asked to present my research findings at the Michael J Fox foundation in New York. Everyone around me was sharing their data from brains and neurons and when it got to me, I stood up to give a talk about lungs! Even though I didn't understand all the nuances of the complex neuroscience findings, this experience enabled me to visualise where the important gaps in the field were, and where my expertise could help.

Exchanging ideas with Parkinson's specialists was of course integral to this project, but it also wouldn't have been possible without collaborating a little closer to home too.

At a macrophage conference in 2016, I had a beer with Matthias Trost, who was independently investigating the role of LRRK2 in macrophages. We decided to have an honest chat about our findings and discovered that we had very similar data but in different systems!

As a scientist, you do your best to test your hypotheses but you will always have some doubts about whether other labs will be able to repeat your experiments and get the same result. Finding out that an independent lab had similar data made us confident that we were on the right track.  

But of course, there was the problem of who would publish their results first.

We decided to join forces and together with Anetta, a post-doc in Matthias' lab, and Susanne, a post-doc in my lab, we finalised the remaining experiments that made the link between LRRK2 and phagosome function for first time, making a key contribution to the biology underlying Parkinson's.

I've learnt that it is much more stimulating to join forces rather than compete. I believe that scientific discoveries can be accelerated if we work together, rather than against, each other.

I am so happy that Matthias and I decided to go the way we did and this has clearly been an eye-opening experience for me. It has been a pleasure working with him and we now have more projects in collaboration.

Many things have changed since then and there is now a growing understanding of the overlap between Parkinson's disease and infection.

Our work raised new questions and we will continue addressing them in the lab. Watch this space!