Interview with scientist – Dale Martin

Welcome to this week’s eLife Ambassador interview with scientist series. We had a pleasure talking to Dr. Dale Martin. Welcome Dr. Martin and thank you for taking time to talk to us.

Dr. Martin is originally from Halifax, Nova Scotia, Canada, but moved every few years while growing up and lived in Montreal, New Brunswick and all over NS. This helped prepare me for the unwritten rule in science that dictates scientists must move to new cities to demonstrate growth.

He completed his undergrad at Dalhousie University in Halifax, NS. While completing a co-op work term in Dr. Roger McLeod’s lab in the Department of Biochemistry, he was fortunate to meet Dr. Robert Ryan while he was a guest speaker. He offered him a summer position in his lab at the Children’s Hospital Oakland Research Institute (CHORI) in Oakland, California studying the structure and function of the then new apolipoprotein AV. Upon completing his undergrad, he wanted a break from school, so he returned to CHORI for a year to work as a technician in the lab of Dr. Ryan’s former postdoctoral fellow, Dr. Michael Oda. There he studied the structure of lipid-free and lipid-bound apoA-I using electron paramagnetic resonance.

During the development of the detection assays, he found that the protein mutated in Huntington Disease, huntingtin, undergoes a little know modification known as post-translational myristoylation following proteolysis of the protein. Interestingly, this fatty acylated proteolytic fragment of huntingtin promoted autophagy, a process required for the removal of aggregating proteins like mutant huntingtin. This discovery led him to Dr. Hayden’s laboratory at the University of British Columbia in Vancouver, BC, Canada. There, he was exceptionally lucky and met his wife, Dr. Shaun Sanders. Shaun is not only his partner in life, but in science as well. Several of their papers and projects have come from discussing research over dinner or while out at a pub. He is very fortunate to have her in my life.

Dale Martin

After Shaun graduated from UBC she accepted a postdoctoral fellowship in Philadelphia. Not wanting to do the long-distance relationships that many have to do when they have the “two body problem” he followed her shortly thereafter and joined Dr. Gareth Thomas’ lab at Temple University studying dual leucine-zipper kinase in axonal degeneration. After a brief time there, he was lucky enough to land a faculty position at the University of Waterloo in Waterloo, ON, Canada.

Here, he will be starting a program looking at how the highly dynamic post-translational modification involving the addition of palmitate, palmitoylation, to regulates autophagy in neurodegeneration. He is interested in learning how stress and diet may alter palmitoylation of these proteins.

Let’s start with you telling us something about yourself

My name is Dale Martin. I am originally from East Coast Canada. I started doing research as a co-op student at Dalhousie University in Halifax, Nova Scotia, Canada. My first project was studying lysosomal multidrug resistance proteins in yeast with the late Dr. Douglas Hogue. My next two co-op positions involved structure-function analyses of apolipoproteins B and A-V with Drs. Roger McLeod and Robert Ryan, respectively. One of these jobs took me to the Bay Area at the Children’s hospital Oakland Research Institute (CHORI) in Oakland, California. After I graduated from Dalhousie, I returned to CHORI for a year where I researched the structure of lipid-bound apolipoprotein A-I using electron paramagnetic resonance (EPR). Subsequently, I decided to return to Canada where I joined Dr. Luc Berthiaume’s lab in the Department of Cell Biology at the University of Alberta in Edmonton, AB, Canada. There I developed a non-radioactive labeling assay for the detection of myristoylated proteins. Myristoylation involves the covalent addition of the saturated fatty acid myristate to N-terminal glycine residues. Until relatively recently, it was only thought to occur on nascent polypeptides as they are translated on ribosomes. Then the late Stanley Korsmeyer’s lab showed that the pro-apoptotic protein Bid is myristoylated on a newly exposed glycine of the new C-terminal product after caspase cleavage. Interestingly, the whole protein remains intact through non-covalent interactions and the new lipid moiety directs the protein to the mitochondria to promote cell death. While investigating the role of posttranslational myristoylation of caspase cleaved proteins, I identified a small domain within huntingtin (HTT) that is post-translationally myristoylated and promotes autophagy when overexpressed in cells. Autophagy is required for the removal of damaged organelles and toxic proteins like mutant HTT, the causative agent in Huntington disease (HD), a progressive and devastating neurodegenerative disease. This finding was one of the first to suggest that the normal function of HTT may play a role in autophagy.

What’s your area of research?

The identification of HTT as a potential modulator of autophagy led me to Vancouver, BC, Canada where I joined Dr. Michael Hayden’s group at the University of BC to study the role of autophagy in HD and how we might be able to exploit autophagy to promote the removal of the mutant HTT protein. My approach involved looking at multiple post-translational modifications (PTMs) of HTT including myristoylation, caspase cleavage and palmitoylation. Palmitoylation involves the reversible addition of the saturated fatty acid palmitate to cysteines of proteins. Along with promoting protein-membrane interactions, the lipid group also promotes protein-protein interactions and conformational changes of proteins. It is a very dynamic PTM similar to phosphorylation.

Subsequently, I joined Dr. Gareth Thomas’s lab at the Shriners Hospital Pediatric Research Center and Department for Neural Repair and Rehabilitation where I applied my knowledge of fatty acylation to axon degeneration and drug screening.

I will continue many aspects of my latest work on palmitoylation in neurodegeneration in my own lab in the department of Biology at the University of Waterloo. My research will focus on the role of palmitoylation in directing autophagy regulators to membranes and how this affects autophagy in neurodegeneration. I am particularly interested in proteins that we know are mutated in diseases like HD and ALS.

What do you think about the current publication trend?

This is a big question. I think there are some great trends opening up like open access and preprint servers. In contrast, there are definitely some very troubling trends. I think many people misunderstand ‘publish or perish’ for ‘only publish in high impact journals or perish.’

Is publish or perish a valid statement for young scientists?

Yes, it is, at least in academia. But I think there needs to be more emphasis on publishing good quality and reproducible science than publishing in high impact journals. If you focus on doing good science, people will find it, read it and cite it.

What do you think of preprint servers? Do you think they are useful?

I think they are incredibly useful. My co-authors and/or I have deposited our last 3 publications on BioRxiv and I plan to continue to use BioRxiv in the future. For 2 of the 3 archived papers, I think it helped protect our research from being scooped. Considering that it can take over a year just at one journal, I think preprints can also help for job and grant applications, particularly for young scientists that might have several papers in various stages of submission. They show progress and indicates that a paper has been submitted while allowing hiring or granting committees to evaluate the work prior to publication.

Do you think science is communicated well to non-scientists? What are some ways to improve science communication?

I think science is much better communicated now than it has been in past years. I think researchers are more comfortable with promoting their research on social media and I think they are more supportive of trainees that want to share both their research and their experiences. A great example of this in the HD field is HD Buzz, started by Drs. Jeff Carroll and Ed Wild. Now, there are many scientific contributors helping to break down recent publications in HD research for patients in multiple languages. They also help tone down some of the hype in the media surrounding over interpreted data.

Dr. Rachel Harding, also known as @LabScribbles, shares her research almost in real time with an open lab notebook that she publishes on Zenodo. She posts everything from the bench to the publication.

While I was a postdoctoral fellow in Dr. Hayden’s lab, we hosted lab tours for HD patients and their families where we gave lay presentations of different areas of research going on in the lab. I think that this was helpful for both the researchers and the patients. It opens the research to the patients and allows them to ask questions that sometimes don’t occur to the researchers.

Personally, in my own lab, I would like to have vlogs that highlight the day to day struggles and successes of research. The scientific process is neither easy nor straightforward and I think both scientists and the public can benefit by acknowledging and understanding this fact.

Overall, I also think learning how to communicate your research to broader audiences also helps us as scientists. You should really be able to explain your research to anyone.

As we know, there are more PhD’s graduating every year as compared to available tenure track positions. Do you think there is way to improve this?

I don’t think it’s necessarily a problem. I think we need to promote alternative careers other than just tenure track jobs in academia. It’s not for everybody and there is nothing wrong with that. There are so many other career options other than academia. If it’s not something you want to do than you shouldn’t be forced to do it.
What are alternative career options for young scientists apart from applying for tenure track positions?

Everything and anything they want. Personally, my goal as a PI is to help make critical thinkers and good scientists that can apply their skills however they want. Ultimately, science impacts many aspects of our lives and, in turn, it is impacted by many other facets. For instance, it can be difficult to convey science without illustrations, so science needs art. Science also inspires art. Cajal’s work is a perfect example of this. We also need lawyers for licensing and patenting, etc., and as science reaches more areas, we need more people to communicate its effects in all of these domains, so we need science communicators. We also need administrators that understand the challenges that researchers encounter on a daily basis. And we need more law makers that have scientific backgrounds. The more research trained people we have in these positions the better.

Apart from science, what do you enjoy doing the most?

Over the past few years, cooking has become my new hobby and passion. It’s actually a lot like being in the lab in the sense that once you understand how things work and you build a flavour palette, it really opens up what you can do. I find that it lets me be creative while doing something I need to do anyway.

What do you think is a recent scientific invention which has changed the way we do science now?

I am going to take some artistic liberty here. I think it’s difficult to state one invention that has changed all areas of science since “science” really encompasses so many different fields that don’t all overlap. However, I think social media, and perhaps Twitter, is the one invention that is changing how we do ‘science’ by integrating multiple disciplines, or at least the scientists themselves, together. On Twitter, I interact with a large variety of scientists outside of my narrow field. That exposure has given me insight into different fields, techniques, and approaches to research. It has helped me build an incredibly diverse network of patients, scientists, reporters, science communicators, and artists that I have found to be very supportive, not just scientifically, but really in all aspects of work and life. The Science Twitter community can be pretty amazing. These people will also lift you up when you feel like you’re failing, they’ll celebrate the good results and all your moments, even when they feel small.

It was a pleasure speaking to you Dr. Martin. We wish you the very best with your research and with your tenure track position at the University of Waterloo.

 

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