Humans of Biology : Dr. Rima Manessa

Would you like to introduce yourself and your field of work?

Sure! My name is Rima Menassa and I work as a scientist at Agriculture Canada. I work in the field of producing recombinant proteins in plants and lately I have been focused on producing vaccines and antibodies for animal diseases. We do this because as Agriculture and Agri-Food Canada scientists, our mandate is to help farmers. We know that farmers who grow animals for food have problems with various diseases, so the idea is to try to produce relatively inexpensive vaccines that they can use to vaccinate their chicken, pigs or cattle.

How did you get involved with Agriculture Canada?

That’s an interesting story, actually. I was doing my PhD in plant molecular biology at McGill and I heard a talk by someone who had a company that produced recombinant proteins in plants – that totally inspired me. As I was finishing my PhD, I saw a post-doc job ad in London, Ontario to work exactly on that. I applied and got the job. So I came in as a post-doc, which lead to a permanent scientist position 5 years later. I consider myself one of the very lucky people who did not really have to go looking for a job after finishing their post-doc.

How do you like Western?

I like Western. I like the department of biology quite a bit. I have had many students from the department in my lab who are PhD, masters, and fourth year honours thesis students. I’ve had other students from other universities and I find that Western graduates do better than others. So, you have a really good program here in biology. I also participate on a lot of student advisory committees like the graduate education committee and my experience has been great.

What does your day-to-day look like? What do you beyond work?

I’m lucky because at the government we don’t have to do teaching or administration. So, we end up with approximately one third of the complexity of what the professors do here – basically all we do is research, which means that we are expected to publish more than university professors, but also to interact with the agricultural industry and help them address their problems.In any given day, I spend a lot of time discussing our research with students and staff, reading and writing papers, research proposals, reviewing papers, theses, and external proposals. I also spend time in meetings, often by phone, with various collaborators, such as a biotech company in Guelph on testing one of our candidate vaccines, and  biweekly lab meetings. I also participate in running the graduate student seminar series.

As for my hobbies, I like biking, cross-country skiing, going to the gym. I also like to watch live theater in Stratford and in London.

With a background in molecular genetics did you experience or witness within science a significant transition to synthetic biology?

No, I wouldn’t say so. In fact, I think that it was a natural transition. We started by producing proteins that were naturally occurring, then found that for getting an immune response we probably only needed to produce some antigenic epitopes. [An antigenic epitope is the part of a protein that induces an immune reaction in the animal]. Then, we looked at ways to display them, so it was a natural progression. We first looked at the soluble proteins and then we thought it would be better if they were displayed on the surface of a particle. So, we made virus-like particles and then began to work on nanocages, which are proteins that exist in microorganisms that live under extreme environments. These proteins are composed of multiple subunits that self-assemble with excellent precision into a caged structure. We thought that on the surface of the cage we could insert 24 epitopes, which would interact with the immune system to trigger an immune response. This would protect the animal from the disease that we got the epitope from.

I realized a few years ago that I couldn’t do this all by myself, so I convinced management to hire a structural biologist who understands proteins and he (Chris Garnham) actually came up with the idea to use nanocages.

I find it interesting that you actually use plants in your research in developing vaccines and antibodies against animal viruses, what are the advantages of using these models? 

Well, there are many answers to this question. The first and easiest answer is that I’m a plant biologist, so that’s the first thing I would think about because I started in this field using plants. But as we have progressed, we’ve found that we cannot produce some proteins in plants very well. So, my thinking changed in that what I’m interested in is the end product and not so much how it’s made. And so, I collaborated with my colleague Chris Garnham (the structural biologist) who works with E. coli while I work in plants. We produce the same proteins and whichever system works best, then that is the one that we will take forward for making the vaccine. However, we have also, through our collaborative experimentation, found that there are many proteins that he cannot make in E. coli that we can make very well in plants, so plants have several advantages. One of those being that plants are eukaryotes whereas bacteria are prokaryotes. Viruses invade eukaryotes and they use the eukaryotic translationmachinery to make their proteins. Oftentimes these proteins require posttranslational modifications that help in folding and stability, and prokaryotes just cannot perform them. On the other hand, if a protein can be made in E. coli, there is no point in trying to make it in plants because E. coli is a cheaper and better developed system..

What is molecular farming? How does synthetic biology tie into it?

Initially this term was used to produce all kinds of proteins, including proteins for human therapeutics.  The idea was that these plants were going to grow to produce value-added crops because they had these pharmaceutical compounds in them, which would allow farmers to make more money. But soon as this field developed, we realized this could be a problem for the environment because of the possibility of spreading transgenes from the planted crops. And so, everyone working in this field moved into greenhouses, and that’s how I kind of morphed into focusing on the end product for animal health rather than the plant agriculture aspect.

As for the role of synthetic biology, it depends on how you define it. Some people define synthetic biology as totally new organisms. I know that Dr. Karas in biochemistry is trying to produce yeast with novel chromosomes in which he will encode new biosynthetic pathways or develop new organelles in plants. The way I understand synthetic biology is something that is not found in nature. The nanocages that display epitopes that we are making right now do not exist in nature. The antibodies that we are making where we grafted a llama binding site to a bovine fixed chain does not exist in nature. So, these are all synthetic molecules that we are producing in plants – that’s how I see synthetic biology fitting in this.

What has been the most rewarding part of your research?

Whenever you succeed at something. When you formulate a hypothesis or you have a goal of making something, when you succeed at producing it, it gives you a huge high. In research usually 90% of what we try does not work so there are a lot of failures, which makes the few successes very powerful. In my career, I will be successful if I am able to bring to market 1 or 2 of the vaccines that I work on. Because the process is so complicated – you have to go through animal trials, regulation, getting a company to commercialize it.

But in my everyday life, my biggest reward is having students in the lab who are interested and motivated and who succeed in their projects – that is immensely rewarding for me.

What advice would you give to students looking to pursue a career in research?

Well if you want to do research you got have to have thick skin. You’ve got to be able to turn a negative result into positive thoughts. By that I mean that if something doesn’t work, you have to try to figure out why it doesn’t work. And so oftentimes when we write a research proposal we develop a goal, but very early on we realize our plan will not work. So, we diverge into something totally different but just as interesting! If you want to do research, you have to be able to troubleshoot, to think positively about something that didn’t work. You have to find a way – through reading literature, through thinking about it – to and learn from it and take it forward.

 

Dr Rima Manessa studies recombinant DNA at Agriculture Canada, to find out more about her research follow the link here.

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