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Profile of Julie Lefebvre

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Dr. Julie Lefebvre, PhD

By: Mackenzie Hill-Strathy

Dr. Julie Lefebvre, PhD

  • Scientist, Neurosciences & Mental Health
  • Assistant Professor, Department of Molecular Genetics, University of Toronto

1. Where are you from?/Where did you study?
I am originally from Cornwall, which is in Eastern Ontario. I went to McGill University and completed my undergraduate degree in physiology. Then I moved to Philadelphia to complete my PhD in cell molecular biology with Michael Granato at the University of Pennsylvania. There, I studied neuromuscular development in zebrafish. After that I went to Boston for my postdoctoral fellowship in the laboratory of Josh Sanes at Harvard University. In December 2013, I moved to Toronto to begin my position at SickKids.

2. What are you researching right now?
I am interested in understanding how the brain develops. I investigate how different types of nerve cells develop and form precise connections with other neurons to build neural circuits. There are a huge number of distinct types of neurons with different functions. The proper assembly of these neurons into circuits is critical in developing a normally functioning nervous system and brain. My approach is to study molecular pathways that regulate the formation of these specific connections. To do so, I use a variety of genetic tools and microscopy to visualize the structure of developing nerve cells and circuits in the mouse retina and brain. Through my research, I hope to gain a better understanding of the molecules and genetic pathways that are important to the development of neural circuits. This can be used to gain insights into how defects in these processes underlie disorders such as autism, schizophrenia, and epilepsy.

3. Who is your all-time favourite scientist and why?
My all-time favourite scientist is Seymour Benzer, a pioneer in neurogenetics. In graduate school, I saw him give a talk on his work, and I learned more about him in his biography ‘Time, Love, Memory’. Benzer was a molecular geneticist who embraced the fruit fly as a model system to understand how genes influence behavior. Through many decades of really important work, Benzer and his many excellent trainees, made the foundational discoveries in identifying the genetic bases of behaviours in fruit flies, such as their circadian rhythms, mating rituals, attraction to light and avoidance to other stimuli. They generated flies with defects in these behavioural responses, and then used genetics to understand what genes are defective and what their roles are in the larger context of the development and function of the nervous system. They also developed techniques to study neural wiring that are still used today. The capacity to sequence genes came later but it turned out that many genes and pathways are conserved in other organisms and in humans, making Benzer’s work very significant in modern neurobiology.

4. What in your opinion is the most important scientific breakthrough and why?
Understanding how neurons and their electrical properties work is crucial in my field. This began when Luigi Galvani discovered that when a frog leg nerve was shocked, the muscle twitched. In the twentieth century the science progressed so much that we now know that neurons conduct electricity and that patterns of neural stimulation are the basis for nervous system function. There are some fantastic scientists who further investigated electrophysiology, such as Gasser and Erlanger who measured the small discrete neural electrical signals in nerve fibers. Huxley and Hodgkin furthered research in the field by demonstrating that dramatic changes in electrical signals give rise to neuron firing and neural information is represented in electrical firing patterns. Now, there’s a new class of research tools called ‘optogenetics’ that enable neuroscientists to manipulate and analyze electrical properties of select neurons. This approach is leading to rapid advances in understanding how neural circuits function and holds therapeutic potential for nervous system disorders.

5. What are your major interests outside the lab?
I am an avid cyclist and runner. I began cycling competitively as a grad student, and continued throughout my postdoctoral fellowship for fun. In the winter my husband and I also love to go cross-country skiing. Most recently, we’ve been doing a lot more running and exploring the amazing network of paths through Toronto in preparation for our first marathon.

6. Why science?
What attracted me most to a career in science is the process of discovery. As a scientist you ask a question, devise the hypothesis and come up with an experiment to try to find the answer to the question. I enjoy this curiosity driven process. In my first year in undergrad, I became interested in scientific research as I found the most captivating part of my courses were those presenting emerging biological concepts, beyond textbook material. Through my research experiences, I was drawn to genetics and microscopy to investigate how the nervous system develops. I’m fascinated with brain development and I want to understand how neurons become interconnected and how defects might underlie neurodevelopmental disorders. I find this very exciting and stimulating!

7. Why SickKids?
There are two main reasons. The first is that I got the impression it was a very collegial and collaborative place to work. I felt I would be surrounded by colleagues who would support my early years as an investigator, and also that it would open doors to pursue new avenues through collaboration. Although I use primarily molecular genetic approaches to study the development of the nervous system, I’m surrounded by people who study electrophysiology, behaviour and genomics. These other areas of expertise open doors to pursue new directions.

The other reason I wanted to work at SickKids was because this is one of the best paediatric hospitals, and I’m surrounded by some of the best human geneticists and clinicians. This environment is important in shaping my future research endeavors. Although I study fundamental neurobiology, I want to be able to apply that to a clinical setting; to understand what early defects in neuronal development can tell us about genetic disorders such as autism. There is so much new knowledge being uncovered about specific genes that are implicated in various brain disorders. We don’t know the function of many of these genes and how gene defects lead to faulty circuits; my research can address these questions.

8. What is the most controversial question in your field right now?
Neuroscientists are really eager to figure out how the human brain functions and to advance the way we treat brain disorders. The biggest debate (which is also something that motivates us to do better science) comes down to what is the ‘best’ approach and what is the ‘best’ model system. Some scientists think we should be studying gene function in systems that we can experimentally manipulate, and some think we should be studying neural networks in whole animals, or better yet humans. The debate as to which questions and approaches are most important seems to be getting more heated as we compete for limited funding dollars and as new initiatives are being created to understand the human brain, similar to the Human Genome Sequencing project. I believe we need to take multi-level approaches in a variety of model systems. Major advancements will come through the integration of all these different strategies.

9. What are you reading right now?
I am reading two books right now. One is a biography that my attorney husband recommended on Clarence Darrow, who was a famous criminal defense attorney in the US in the late 1800’s and early 1900’s. He defended very prolific cases, and in many cases his clients were poor and had already been deemed guilty by the public. He was also involved with the famous Scopes ‘Monkey’ trial that addressed a ban on teaching human evolution in schools and the conflicts between modern science and religious beliefs. This case attracted a lot of attention from the public and the media. These issues are still very much relevant today. The other book I am reading is At the Helm, which is a book written for scientists about how to set up their own labs. This is something I am finding useful, as I am in currently in the process of setting up my lab.

10. If you could give one piece of advice to someone considering a research career, what would it be?
Science is becoming increasingly multi-disciplinary, so it is important to learn other fields and be familiar with their methods. It is easy when you are starting your research career to focus on your specific area of expertise; you want to be very knowledgeable of your domain, the current literature and experimental methods that are available. However, increasingly there is more overlap and collaboration between scientific disciplines. The questions are becoming a lot more complex, and being able tackle a research problem from different directions is increasingly important. I would recommend attending seminars and reading papers on subjects that are either not in your field, or might overlap by examining a different experimental approach.

11. What does the SickKids' Peter Gilgan Centre for Research and Learning (PGCRL) mean to you?
I am really excited about this building because it has brought everyone together. Not only am I close to fellow neurobiologists, but I also get to work with individuals with overlapping interests such as cell and developmental biology and genetics. This building puts my lab in close proximity to other labs studying similar questions but taking different approaches and might lead to entirely novel collaborations. This all comes down to the multidisciplinary environment of the PGCRL. I’m also excited about the potential to collaborate with clinicians. As I am new here I have just begun reaching out to these individuals, and I see a great potential in working with them in the future.

November 2014

Scientific profile