Researchers Under the Microscope

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Dr. Simon Chen

Canada Research Chair in Neural Circuits and Behavior

After completing his postdoctoral studies at the University of California, San Diego, Dr. Simon Chen took on the role of Canada Research Chair in Neural Circuits and Behavior and established his new lab at the University of Ottawa with a focus on using two-photon imaging to study how the brain changes during learning. With his research resulting in first-author citations on papers in Cell, Neuron, Nature, and Nature Neuroscience, Chen continues to inspire us as he uses advanced methodologies and collaboration with uOttawa professors to extend his research further. We sat down with him to get to know a little more about the man behind the research:

OSURJ: Why did you choose research as profession? Did you consider other professions?

SC: I did. So I started working in the lab when I was in 3rd year. And at that time I really wanted to go into pharmacy or med school. But after I worked in the lab I just really enjoyed the passion that people have. You’re surrounded by masters, PhD students and they talk about science every day. And another thing I really like is the hours: I’m that type of person that doesn’t like to go to a job from 9 to 5. I really enjoy the flexible hours that you get from working in the lab. It’s by responsibility -you have a project, you know you have to get it done, and you can choose to work on whatever schedule you like. You can come in morning, night - as long as you get it done. Whereas a lot of jobs, I find, talking to my friends, they start from 8-4, 9-5, sometimes overtime. That’s why I really enjoy research. Just the conversation with the colleagues, that felt really different when I was in undergrad.

OSURJ: As an undergraduate student any pieces of wisdom that your past teachers/mentors gave you that has stuck with you?

SC: You would rather work smart than hard. In any job, (students) think "if I put enough hours in I’ll get the return." But that’s not how it works in science. You need to be thinking while you’re doing the experiments and observing so you can change things in between to have the maximum outcome. I find that sometimes a lot of students think that if I just come here and do the work I’ll get a return. I always tell students that you’d rather work smart than hard. As a PI, I don’t care how many hours you put into the lab. If you work smart and get good conclusive results, even if negative, it’s meaningful. But if you tell me you work 10 hours in the lab everyday but your data is all over the place, then that work almost means nothing. So you want to work smart not hard.

OSURJ: Can you describe an embarrassing or funny moment as a grad student or undergraduate student?

SC: The most embarrassing thing that happened to me was when I was undergrad... same lab I did my PhD in, I remember the first time I presented at the lab meeting and showed the plot with error bars. My PhD supervisor asked me “How did you get the standard error bar?”. I just said “I used Excel and they have this function called “Standard Error Bar”” and my supervisor just went crazy. That’s probably my most embarrassing moment [laughs].

OSURJ: What inspired you to start in your current research field?

SC: So the long-term goal of my research is always on learning and memory. And what drives me to this particular research is technology. So I think it’s really important, especially in neuroscience, that you bridge technology with basic science. One of the really cutting-edge techniques we use in our lab is two-photon imaging. This two-photon microscope was only developed in the early 2000s. You use a really advanced laser to image in deep tissue in the brain. In normal microscopes like confocal, light cannot penetrate the brain tissue; it gets scattered out before getting 200µm into the brain. So with this two-photon, it can be used after 1mm into the brain and also in awake mice. This allows you to study learning and memory in live animals. Back in the day when people studied learning and memory, they studied behavior but didn’t know how the brain was changing  - or in culture, where they saw neurons changing but didn’t know the behavior. Now with this technology of the two-photon microscopy, you can bridge the two and see how the mice are changing as they do a task.

The one downside is that the mouse has to be head-fixed on the stage, limiting the behavior tasks we can do. Everything we do in our lab is built by our electrical engineer. It’s not commercially available. So we can change different parameters of the behavior test based on the question we want to ask.

OSURJ: What is your favorite aspect of being a researcher? Is there anything you dislike?

SC: Dislike would probably be writing grants. [laughs] That’s always the hardest part.

My favorite part [about research] is when students bring you data that you don’t expect. And this is actually what drove me to continue science during my PhD. I ran a Western gel and we had a control, a treatment that we thought was supposed to change, and another treatment that we thought was a control as well. The gel showed that there was no difference for the one treatment but the other treatment changed. We repeated this 5 times and the results were always the same. We derived a completely new project based on that observation. And that got into Cell in 2012.

And then with my own lab now too, we have a story about autism. Not something we hypothesized, but during the summer, one of the undergrads did staining and we saw a change that we didn’t expect. So now the whole lab is geared toward that finding. So you can never hypothesize what you expect. That’s science. You always get new data and you interpret the new data and derive the new stories out of it.

OSURJ: What made you decide to come to uOttawa? What is it like being a new professor?

SC: I got two offers in the US and also from Ottawa. I think Ottawa is one of the rising research universities especially in neuroscience. We have a really strong Brain Mind Institute. Also they offered the biggest startup in Canada. So in order to buy that two-photon microscope, it cost $700 000 Canadian. More than my house [laughs]. And they’re the only school in Canada that can afford that startup. And I’m a Canadian so I always wanted to return to Canada and do my research here.

OSURJ: Can you think of any common research misconceptions?

SC: A lot of people think that a masters or PhD is more about knowledge. But it’s more about endurance. I always tell my students and younger grad students that doing grad school is not a sprint. You can’t just work really hard and think that it’s going to be over soon. Doing a PhD these days takes almost 6-7 years. It’s a marathon. Even today, you get really good results, you write a paper and submit it. From the moment you submit a paper till your paper gets accepted, it can take up to a year, year and a half. So a lot of students are burnt out by the time their paper is submitted. But they don’t understand that when the revision comes back, you need more energy again to do more experiments to the last sprint. So in some ways it’s like a marathon. You do it, get tired and think you’re done but you have to do a sprint that you have to go through to get it out.

OSURJ: What do you look for in prospective students who want to work in your lab?

SC: We’re always looking for students. We always welcome undergrads and currently we’re looking for other masters or PhD students.

I look for responsibility and independence. One thing - in our area particularly - for our work is that you need to be responsible for your project and always have to plan ahead. We do a cranial window and wait two weeks before we can water restrict the mice (and that’s another two weeks) and then we train the mouse for another two months. So if you’re a person who isn't really independent or responsible, you don’t plan ahead. Then one day you come to me and say you don’t have mice because you didn’t do the surgery two weeks ago. Once you didn’t do that, you've basically lost two months of work. One sixth of the year is gone. In our lab, I really look for these aspects in students. They need to be really organized, responsible, and able to plan ahead so they know what to do every week.

OSURJ: But that’s tough to screen for before seeing them work in your lab right?

SC: Yes, that’s why I guess the turnover rate would be high. I take students and if they don’t show those aspects I probably won’t keep them. 

OSURJ: Are there any new cutting-edge methodologies that you are excited about?

SC: We’re now doing this technique called rabies tracing. So rabies, as you know, is this disease that you get when bitten by a mad dog. It’s a really unique virus in that it jumps synapses. It goes from your finger’s nerve terminal and jumps a synapse to a motor neuron and all the way to your brain. Scientists in the US made a modified version of this rabies. They take the toxicity out and modify the genome of the rabies so it can only jump one synapse. So now this has become a really powerful tool to do circuit dissections. Now you can imagine there are five cell types in the motor cortex and I want to know where cell type A receives its inputs from. Is it from the somatosensory cortex, the striatum? You use this pseudotype rabies virus, you express it in cell A, and then the virus will only jump one synapse to where it receives its input from. So now you can know exactly where in your brain your cell receives input from. That’s what we’re working on in our lab right now.

OSURJ: If you won lottery what would you do? Let’s say like a $100 million prize.

SC: I would probably put half into my lab. Because probably to run our lab without any stress is $500 000 per year. So if you put $20 million in, you could function for 40 years. And the rest would be for family. And wine [laughs].

OSURJ: What pieces of advice can you offer to students looking to pursue a career in research?

SC:  I would say you need passion. If you find interpreting results is just like washing dishes and like a normal job, then this is not a good career for you - for research, you really don’t get good pay until you become a professor. And often compared to your classmates or friends in the same year, they go into engineering or business and right out of undergrad they’re making 50 or 60k whereas if you become grad student, you’re making 20k. If you have really good grades, you probably get a scholarship and make 30-35k. Then you become a postdoc (and that’s 6 years after you graduate from undergrad) and at that time you’re making 40k. So in the first 10 years after you finish your undergrad, you’re not really making that much. You really need that passion to keep you going. Otherwise if you just compare yourself to your friends, you’ll find it hard.

This interview has been edited for clarity.

If you are interested in joining Dr. Simon Chen's lab, please contact him at schen2@uottawa.ca.