Clary Clish

#WhyIScience Q&A: A microbiologist and immunologist finds links between our own microbes and disease mechanisms

arinavetta — Tue, 15 Oct 2024 18:32:38 +0000

#WhyIScience Q&A: A microbiologist and immunologist finds links between our own microbes and disease mechanisms

By Ari Navetta October 15, 2024

#WhyIScience Q&A: A microbiologist and immunologist finds links between our own microbes and disease mechanisms

Eric Brown discusses finding purpose in the unpredictability of research and his personal connection to his work.

By Ari Navetta

October 15, 2024

Credit: Allison Colorado, ӳ��ý Communications

Eric Brown is studying the links between the microbiome and disease.

Though his focus shifted over time, being a scientist was always the plan for Eric Brown since kindergarten. “First it was dinosaurs and whales, and then it turned into birds, and then it turned into microbes,” he said.

Years later, Brown began studying structural biology as an undergraduate student at the University of Guelph in Ontario, Canada. But it was working in another lab where Brown became fascinated with the vast world of the microbiome and its complex relationship with our bodies and health. He investigated using probiotic bacteria as a possible treatment for C. difficile colitis, a severe bacterial infection in the colon that frequently resists antibiotics.

In 2015, while pursuing a PhD in microbiology at the University of British Columbia, Brown received a scholarship opportunity to work abroad for a summer. He reached out to Ramnik Xavier, core institute member and co-director of the Infectious Disease and Microbiome Program at the ӳ��ý of MIT and Harvard, and continued collaborating with Xavier and Brown’s PhD advisor following that summer. After completing his PhD in 2017, Brown joined Xavier’s lab as a postdoctoral researcher and has been at the ӳ��ý ever since, now as a staff scientist.

We spoke with Brown about his experience as both a researcher and a patient in this #WhyIScience Q&A.

What are you working on right now?

The Xavier Lab looks at interactions between microbes in your gut and your immune system, and diseases such as arthritis and inflammatory bowel disease (IBD). Microbes can shape our immune response, and we’re trying to understand what T cells are involved in that process and how it plays into chronic inflammation. For a lot of this work we collaborate closely with Clary Clish and the Metabolomics Platform.

Many risk genes require an environmental trigger to cause disease. I’m researching a disease called ankylosing spondylitis (a type of arthritis that affects the spine) because there’s overlap in people who have it and people who have IBD, and both are linked to a common variant of the gene HLA-B27. About 6 percent of the U.S. population has this variant of HLA-B27, and it gives you approximately a 200-fold increased risk for types of autoimmune arthritis, where your immune system attacks your joints and causes inflammation. In a related disease called reactive arthritis, a bacterial infection triggers arthritis, and you’re much more likely to get it if you have this form of HLA-B27. We’re looking to see if ankylosing spondylitis works in a similar way and might be triggered by microbes in our gut that become systemic and create this inflammation in the lower back.

I was recently diagnosed with ankylosing spondylitis and, with support from Ramnik, we started the project two and a half years ago. Reading about it, I realized we don't know much about the immunological mechanisms of the disease. As a microbiologist and immunologist, I started thinking, given our capabilities in understanding genetic links and microbes in IBD, which we study a lot in the lab, we are well positioned to make a contribution — let’s work on that. I feel lucky I’ve had that ability to look into it.

What approaches are you taking to study these questions?

People have been trying to solve this problem for 50 years. The HLA-B27 gene was linked to ankylosing spondylitis in 1973, before we even knew its function. Most of the previous work has been done by rheumatologists, and we’re coming at it from a different approach, leveraging my unique experience and the lab’s capabilities working with the microbiome and IBD.

Recently, there’s been a breakthrough in recognizing the role of T cells in ankylosing spondylitis. We have so many more tools now to study T cells, the microbiome, and the interactions between the two. We use a broad range of techniques, working with animal models, using cell cultures, high-throughput sequencing and flow cytometry. The sequencing depth and access to data we have here are really helpful, and we can analyze cohorts of many people who are HLA-B27 positive and some who have ankylosing spondylitis.

What do you find most challenging about your work?

Science can be really slow and often things don’t work out. A lot of the time, the work you put in doesn't necessarily equal a tangible output. I could try to clone a gene for a year and it might not work, and I have nothing to show for it. But maybe I spend one day doing an experiment and it's perfect. It's not linear. There's a huge iceberg of stuff that isn't communicated because it didn’t work out the way we expected.

What keeps you motivated to keep doing research?

You need a north star purpose in your research so that you can say: maybe things aren’t working right now, but when they do, I’m confident it will matter.

When you publish a paper, nothing really happens at first. But then five years later, somebody cites your paper or you realize that this work was part of something bigger. You realize that what you find and what you publish is timeless. I'm even going back to papers from the ‘70s and ‘80s. It’s motivating to build on knowledge — you’re creating the building blocks for people to learn new things.

Are there any trends you’re seeing in your field?

One is AI and large language models. For this arthritis project, we're trying to find the peptide that binds to HLA-B27 and to a T-cell receptor that’s been linked to the disease. To do this, we’re working in collaboration with Caroline Uhler’s group in the Schmidt Center who are experts at these computational models. With their help, we can better choose which experiments to do in the lab.

Do you have any advice for early-career researchers?

When you’re going towards grad school, try not to see those degrees as a means to an end to a job. Work on something that gives you purpose and that you're interested in — and that might keep changing. Think about the journey, because there's a huge network of people you can meet along the way. There are careers other than academia now. As scientists, often we go into the lab and we put the blinders on, but I don't think we realize the network of people that surrounds us. I still keep in touch with a lot of my graduate school friends who now hold positions around the world, and I’ve found these connections very meaningful in my scientific journey.

Tags:

Immunology Program

Inflammatory bowel disease

Metabolism

Caroline Uhler

Clary Clish

Ramnik Xavier

Scientists work out the effects of exercise at the cellular level

adicorat — Wed, 01 May 2024 15:00:00 +0000

#WhyIScience Q&A: A microbiologist and immunologist finds links between our own microbes and disease mechanisms

By Ari Navetta October 15, 2024

#WhyIScience Q&A: A microbiologist and immunologist finds links between our own microbes and disease mechanisms

Eric Brown discusses finding purpose in the unpredictability of research and his personal connection to his work.

By Ari Navetta

October 15, 2024

Credit: Allison Colorado, ӳ��ý Communications

Eric Brown is studying the links between the microbiome and disease.

We spoke with Brown about his experience as both a researcher and a patient in this #WhyIScience Q&A.

What are you working on right now?

What approaches are you taking to study these questions?

What do you find most challenging about your work?

What keeps you motivated to keep doing research?

You need a north star purpose in your research so that you can say: maybe things aren’t working right now, but when they do, I’m confident it will matter.

Are there any trends you’re seeing in your field?

Do you have any advice for early-career researchers?

Tags:

Immunology Program

Inflammatory bowel disease