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About the Institute

Profile of Roman Melnyk

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Dr. Roman Melnyk

By: Alena Boczek

Dr. Roman Melnyk, PhD

  • Scientist, Molecular Medicine
  • Assistant Professor, Biochemistry, University of Toronto

1. Where are you from?/Where did you study?
I grew up north of Toronto, in a town called Newmarket. I attended Saint Andrew's College in Aurora for high school, and then did my undergraduate training at McMaster University in biochemistry. I then did my graduate training here at SickKids in Charles Deber’s lab as a graduate student. After getting my PhD, I went to Harvard Medical School in Boston where I was a postdoctoral fellow in John Collier's lab for three years.

Next, I did something which was a little different than most, I went to work at a pharmaceutical company in Montreal called Merck-Frosst, where I was a Senior Scientist. I spent almost five years there doing drug discovery, and I saw a whole different side of research and science. Of course, about a year ago I came back here, to SickKids and the University of Toronto.

2. What are you researching right now?
Drawing on my two previous training experiences, drug discovery and infectious diseases, my group right now is mostly focused on looking at bacterial toxins released by pathogenic bacteria during an infection that causes disease. We’re working on Clostridium difficile (C. difficile), which is a big problem in hospitals. In most developed countries, it’s emerging as the single greatest uncontrolled pathogen in hospitals today. It has become an even bigger problem than Methicillin-resistant Staphylococcus aureus (MRSA) in many hospital settings.

So our research group is looking at developing strategies for new therapies to manage C. difficile associated diseases. One of the features of this disease is that it is almost exclusively mediated by toxins. The bacteria secretes toxins in the gut, and the toxin damages the gut lining which produces the symptoms of diarrhea that can develop into colitis, so there is a very clearly defined target in the disease. The idea is to look for toxin-neutralizing therapeutics. To do that, we’re using a lot of the techniques and approaches used in pharmaceutical drug discovery and applying it here.

C. difficile is mostly in hospitals because it’s actually caused by antibiotics, so it’s often also referred to as antibiotic-associated C. difficile. What sometimes happens is that patients in a hospital or long-term care facility develop a bacterial infection, take antibiotics, which wipes out most of the bacteria in the gut. Naturally resistant, C. difficile then flourishes and secretes toxins and that’s how the cycle of disease works. The problem is you can’t treat it with antibiotics because that’s what causes the disease and that’s why we need novel therapeutics that are not antibiotic-based to treat the disease.

One of the things about toxins is that they are exquisitely designed to enter cells. This is important because one of the barriers for efficacy for many drugs is that they can’t get inside cells and reach their molecular targets. So, the other half of our lab will be looking at using toxins to deliver therapeutic cargo into cells. We’re hoping that this so-called synthetic biology approach where we engineer the toxins to deliver good cargo instead of deadly cargo, will be a new platform for enzyme replacement therapy.

3. Who is your all-time favourite scientist, and why?
Linus Pauling is somebody whose approach to science is something that I always admired. He was somebody who was interested in a lot of different things, and where he made his mark in science was really at the interface between fields. I think a lot of the power of discovery comes from drawing on two different things that maybe aren’t connected normally. This is a form of lateral thinking using a creative approach, taking two disparate topics and putting them together to come up with something new that was not obvious. He was a guy who worked on quantum mechanics, chemistry, molecular biology, medicine, and it was really at the interface of all those disciplines where he made a lot of all his greatest discoveries.

4. What in your opinion is the single most important scientific breakthrough, and why?
I think, in the last 50 years, it would be the ability to manipulate DNA, to mutate DNA. Kary Mullis and Michael Smith share the Nobel Prize for their ability to essentially manipulate DNA. Kary Mullis discovered Polymerase Chain Reaction (PCR), and Michael Smith was doing mutagenesis a different way but it completely opened up whole new fields and molecular biology was born out of those discoveries. And, Michael Smith actually gave the commencement speech at McMaster when I graduated and though I didn’t meet him, I got to hear him speak in person, which was great.

5. What are your major interests outside the lab?
My family of course. We have a five-year-old daughter and watching her discover her surroundings and her environment, is kind of this never-ending experiment. It is really amazing to watch how she interacts with the world around her. I take a lot of joy out of interacting with her, and spending time with her.

I run a lot, well as much as I can. Science is a taxing endeavor and one of the things that I’ve always tried to do is stay healthy and exercise as much as possible. I often get my best ideas when I am running. I took up rock climbing in graduate school and it is something that I recently got back into. I think climbing is a lot like science. You can do science and rock climbing in two ways. You can use a brute force approach, which works and will get you to a point, but to get to the next level, you need to be patient, look the problem then be creative and methodical.

6. Why science?
It was really just recognition of how I think and work, and what excites me. What excites me is that science is different every day; we never do the same thing. I was always good at math and science growing up, and I think, like a lot of people, I enjoyed it initially because I was successful at it. But I didn’t get passionate about science until I actually started doing lab work in University. I had some really great professors at McMaster who actually got me thinking about biochemistry and about science outside the textbooks. But I think my passion came the first time I actually got in a lab and got hands-on experience. The ability to create and discover – I don’t think there’s any job like this where you can create. You come to work in the morning and you think you’re going to do one thing, and at the end of the day it’s something totally different and that happens a lot. I think it’s a unique career and it resonates with the way I work and the way my mind works. I like to be challenged and do different things. Science is really a puzzle and we get to be kids all day and solve puzzles. What we do is essentially problem solve every day and it’s fun – it’s a great job.

7. Why SickKids?
I was in a unique position because I had been at SickKids during my training, so I knew a lot about this place. There are really two reasons. One is the people and the second is the environment.

My experience at Merck-Frosst helped me appreciate the power of having multiple disciplines and people with different backgrounds around you. Going back to the theme of working at the interface and between different things, SickKids is a really diverse place for science and it allows you to interact with people who are in different fields and ask questions that are outside your own field.

8. What is the most controversial question in your field right now?
There are two. The first is to do with the relative roles of the two toxins that C. difficile secretes. The two toxins, A and B, on the surface are very similar: they are highly homologous with each other. It’s a little peculiar because they seem to do the same thing, they seem to be redundant. The controversy is which of the toxins is really more important for causing the disease? There were two conflicting papers that came out in the last year in Nature. One paper said it was B the other said it was A and B and they seemingly did the same experiment. From my standpoint, therapeutically, it’s an important question because we have to know if we have to target both toxins, or just one of the toxins – which would be the easier path.

The other really peculiar question in the field is why infants who have toxigenic C. difficile don’t get sick? It’s really not clear why that is: Are they lacking some receptor? Is there something in the gut of infants that’s protecting them from toxins? I think it would be interesting to find out why kids don’t get sick from this bug. The unfortunate thing is that the epidemiology of this disease is changing now and kids are getting sick from C. difficile, but it’s still not as severe as in the elderly. I think there’s an opportunity to ask that fundamental question of why don’t kids get it – that’s really important to know.

9. What are you reading right now?
I am halfway through Steve Jobs’ biography by Walter Issacson right now. It’s a very interesting book because he was a visionary who has become very famous for the technology that’s sitting on my desk, in my pocket, and in my book-bag. His most defining feature was that he was at the head of the pack and knew what people wanted before they did. He had incredible focus on knowing what he wanted and on keeping it very simple. I think there’s a real message there about not cluttering discoveries (or products) and keeping things very simple for people. By analogy I think that’s the way science needs to be communicated. Often concepts in science are complicated, but at the end of the day you have to think about the customer, the patient, the end user, and make the experience a better experience for them by making it accessible.

10. If you could give one piece of advice to someone considering a research career, what would it be?
The advice I would give to somebody is to do it – to go and do science.

One of my greatest frustrations is the misconception about what science is, and what scientists do, and what graduate school is, and what a postdoctoral is. The general public mainly thinks of science as being a very impersonal pursuit with people locked away in a lab and they don’t interact with people. Science is the exact opposite. Science is all about collaborating, it’s about interacting, it’s about sharing your ideas with people.

I think from the perspective of students especially, there’s a real misconception about graduate school; people think graduate school is just a continuation of school – they sit in class all day. But as a graduate student you get the opportunity to do science – you’re not in the classroom – you’re in the lab doing research. That single misconception keeps a lot of smart people from doing science. A lot of people think, “Oh I don’t want to sit in class all day,” but it really is an exciting time. More education has to be put into making people understand what a science career entails. Whereas in medicine I think most people understand what medicine is because they interact with doctors a lot. We’ve all been to doctors, there’s lots of TV shows about doctors, but science is something a little more mysterious.

I think if someone is considering a career in science they should go do it because I think you have to have a certain kind of personality to really enjoy it, and it has to come from a thirst for knowledge. While at the same time, you have to have the stomach for failure. In this job you fail more than you don’t, and that’s part of the job – you move forward by moving backwards sometimes in science. I think a lot of people get really discouraged when they walk in and they try something and it doesn’t work. They panic because they think it’s something wrong with them, but that is what science is all about, the journey to discovery.

11. What does the SickKids Centre for Research and Learning mean to you?
On many fronts, the tower is a big part of my coming here. One, it is certainly going to be a great opportunity to be interacting closely with both new and present colleagues. The tower is designed is to be horizontally and vertically integrated within neighborhoods which is something I’m really excited about. It will enable more of a team atmosphere, and make it easier to collaborate. As I said before I think that’s one of the things that really enables the best science: collaboration – and when you have lot of walls between you and your peers it’s very difficult to collaborate. In that system, you have to be a lot more active to collaborate.

I also think having a really state-of-the-art building is going to help recruit top talent. It’s going to be a really nice environment to work in, it’s going to be modern, and you can’t underestimate what that does to your every day morale. I think people are going to enjoy coming to work every day and I think that’s important for recruiting top people.

March 2012

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