Exploring genetic frontiers: An interview with Andrew Simmonds

We have the pleasure of introducing Dr. Andrew Simmonds, the newly appointed Co-Editor-in-Chief of Genome. Dr. Simmonds is a distinguished Professor and Chair at the University of Alberta, where he earned his PhD. His research is dedicated to advancing our understanding of gene regulation pathways pivotal to human health.

Dr. Simmonds leads a multidisciplinary research group that employs diverse techniques including live-cell imaging, Drosophila genetics, cell culture, and molecular biology. Using this holistic approach, his lab explores how a range of cellular mechanisms—from metabolism to gene regulation at both the transcriptional and post-transcriptional levels—influence organ development. One of his key areas of focus is peroxisomes—small, membrane-enclosed organelles that carry out a variety of metabolic reactions and, when not functioning correctly, can cause several disorders.

In this Q&A, Dr. Simmonds shares insights into his career journey, recent breakthroughs in his lab, and the challenges and rewards of an academic career. He also discusses the vital role of undergraduate students in scientific research and offers advice for those embarking on a career in cellular biology.

Congratulations, Dr. Simmonds, on becoming co-Editor-in-Chief of Genome! You’ve had a very impressive career and we’re curious about how it began. Was there a defining moment or experience that inspired you to pursue genetics and cell biology? 

I actually started my undergraduate degree studying computer science. It was during my second year that I took a genetics course and decided to change my major. For graduate training, I asked my undergraduate mentors where the best genetics departments in Canada were, and I ended up at the University of Alberta for my PhD working on fruit flies. Since then, my research focuses have encompassed transcriptional and post-transcriptional gene regulation and, most recently, organelle co-regulation (peroxisomes and lipid droplets regulation), but all of these are in terms of how these events regulate animal development.

Your lab studies several intricate cellular mechanisms, from peroxisome function to cell fate determination. What’s a recent “aha” moment or breakthrough from your lab that advanced our understanding of these processes?

A lot of our recent research direction came from a chance observation of cells that overexpress a small subset of the Peroxin genes linked to peroxisome assembly. Peroxisomes are normally small, punctate, motile bodies that, among other functions, regulate aspects of lipid metabolism. We saw that a small subset of Peroxin proteins formed large ‘rings’ in the cell and that these rings outlined lipid droplets, which store lipids. A large part of my lab’s work is now focused on determining how some Peroxins have a ‘second job’ coordinating lipid storage along with their canonical function in peroxisome assembly.

Can you elaborate on your work studying the cellular mechanisms underlying peroxisome disorders? What potential implications do your findings have for the diagnosis and treatment of these disorders?

The Department of Cell Biology at the University of Alberta is a long-standing leader in studying peroxisome disorders, led by my colleague Dr. Richard Rachubinski and his groundbreaking work characterizing these organelles in yeast. One day, Dr. Rachubinski poked his head into my office and asked what was known about peroxisomes in Drosophila. It turned out that, despite flies being a model for a multitude of human diseases, there was relatively little work using the fly to model peroxisome diseases. Using the fly, our group, including Dr. Francesca Di Cara (now at Dalhousie University), showed that peroxisomes are required for antimicrobial activity, similar to other studies from the University of Alberta indicating their role in antiviral responses. This alerted those treating patients with peroxisome disorders about the potential for reduced immune function.

That’s a powerful story of collaboration and innovation, not to mention a brilliant example of the value of Drosophila as a model for human disease. In 2023, you co-wrote the introduction to Genome’s special issue containing selected papers from the 15th Canadian Drosophila Research Conference (CanFly), which brought together Drosophila experts from across the country. Can you share a memorable moment or influential partnership that arose from attending conferences like this one?

Many of the ‘big’ papers in my lab have come from collaborations that stem from conferences. The most memorable one would have to be when a leader of a group tracked me down at the poster I was presenting with the opening line, “We have the other half of that story on Drosophila RNAse MRP. We should publish together.”

The CanFly meeting is special to me as Canada is a big country and individual labs do not have the chance to meet in person as often as they would like. My first ever meeting as a PhD trainee was CanFly in 1991. I came out of that conference with a lifelong love of flies as a laboratory animal, a lot of good friends and colleagues, and my spouse of 29 years (still going).

Academic careers are often challenging. There is the stress of balancing research with teaching, the trials of grant applications and, of course, the universal frustration of biological research: experiments that inexplicably go wrong. (That’s not to mention the small annoyances of lab upkeep!) Was there ever a moment that you faced doubt in your career path, and how did you navigate it?

It was early in my career. I actually failed my first attempt at my PhD candidacy exam in 1995 due to a misunderstanding on my part as to what ‘recent’ genetics research meant. The learned (older) members of my committee had a much broader definition of ‘recent’ than I did (ie., going back to the 1960s and 70s). Fortunately, I was given a second chance and after reading a lot of papers from those decades I came back with a new appreciation for that groundbreaking research and managed to pass on the second go around.

When you aren’t teaching, editing, attending conferences, or running a successful lab, what hobbies or activities do you enjoy?

A great part of living in Edmonton is that I can spend a lot of my free time visiting the mountains in Jasper National Park, downhill skiing in the winter, and backpacking in the summer. To relax, I also play recreational hockey. This is actually a new sport that I started after learning to ice skate at the youthful age of 46.

You’re a strong supporter of undergraduate students. Could you speak a bit about how you see the role of undergrads in advancing scientific research?

I see three major roles for undergraduates. The first is to be exposed to the process of scientific research during their ‘formative years’ as they discover themselves and their passions. The second is that in active laboratories there are always projects that need attention and talented undergraduates can have a significant impact. I make it a point to include undergraduates on papers that they have contributed to. Lastly, undergraduates are the future of our field; they provide vitality and new ideas.

What advice—conventional or unconventional—would you offer to students and early-career researchers eyeing a career in cellular biology or genetics?

I tend toward the unconventional when it comes to the advice I give. I guess my most famous advice is to try as many things as you can and make as many mistakes as you need to—once; always learn from your mistakes. I truly believe that genetics and cellular biology are transitioning from ‘legacy’ fields to the ‘future’ of biology and medicine via a landslide of new technologies. Both fields are moving from reductionist approaches to integrative approaches that consider the entire spectrum of processes from transcription/translation to their products and how these are integrated into cellular and organismal functions. It is somewhat trite to say, but unless you understand how things work, it will be prohibitively difficult to properly understand how things go wrong.