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Profile of David Bazett-Jones

Photo of Dr David Bazett-Jones
Dr. David Bazett-Jones

Dr. David Bazett-Jones, PhD

  • Director, Advanced Bioimaging Centre
  • Senior Scientist, Genetics & Genome Biology
  • Professor, Biochemistry, University of Toronto

1. Where are you from? /Where did you study?
I was born in Toronto but grew up in a number of places in Ontario, including Thunder Bay and Woodstock. I attended the University of Waterloo to study physics and then did my graduate studies in medical biophysics at the University of Toronto. That is when I first discovered an interest in molecular biology even though all the work I had done up to that point was in physics. I then did a post-doctorate in molecular biology at Scripps Research Institute in La Jolla, California and my first academic job followed at the University of Calgary.

2. What are you researching right now?
My interest in biology came through the back door of physics and imaging. I became really interested in using the electron microscope to do something that it had never been used for before. Most people think that the microscope can only provide structural information. In fact, it’s capable of producing high resolution chemical information as well. This allows us to look at a cell and be able to visualize DNA specifically within the cell nucleus. By visualizing DNA within the cell, we are gaining an appreciation that each cell type has a unique nuclear architecture and that the DNA is organized in completely different ways in the nuclei of different cell types.

The focus of my lab is to understand how DNA is organized and what affect this has on making one particular cell type different from another. What we’re learning is that “location is everything” in terms of genetic organization. If a chromosome or a set of genes ends up in the wrong location within the nucleus, these genes are not going to be expressed properly and the cell will behave aberrantly. Such errors could be the basis of a cell turning into a cancer cell.

There are currently two areas of focus in my lab. One is to study chromatin organization; chromatin is the molecular complex of DNA and the proteins that package it. Even though the structure of DNA has been known for 60 years, we still have no idea how DNA is packed into the nucleus and this information is critical for determining how one cell type differs from another. We are investigating how chromosome positioning within the nucleus comes about and how specific sets of genes come together into nuclear neighbourhoods where they are regulated together in these local domains. These domains are extremely small structures, sometimes less than one-ten thousandths of a millimetre. By examining their structure with high resolution microscopes, we hope to understand how genes are accurately positioned in the nucleus.

We are also studying other subnuclear entities, such as so-called promyelocytic leukemia nuclear bodies or PML bodies. In promyelocytic leukemia patients, their affected blood cells lack PML bodies. These were discovered in the 1980s but nobody knew at the time what they were. In the 1990s, it was discovered that the protein that made up these structures in the nucleus was mutated in this form of leukemia. If cells from patients are treated with retinoic acid, which is now a standard therapeutic agent, the PML bodies re-form and the cells become normal. Fortunately, 85 per cent of patients who are treated with retinoic acid go into remission.

What we are trying to uncover is what these structures do in the nucleus. Our lab is gaining evidence that they serve as hubs where specific sets of genes congregate and we think the genes that come together at PML bodies, are either activated or repressed accordingly by being in this location. The nucleus is a highly organized structure and if PML bodies are abnormal due to mutations, this has profound consequences for the health of the cell. Again, nuclear structure is critical, and for a gene, “location (in the nucleus) is everything”.

3. Who is your all-time favourite scientist, and why?
Sir Isaac Newton. There’s no question about it! He was a genius and his theory of gravitation lasted 300 years before anyone dared to touch it. Only with modern technology could we go back and revisit his theory. Newton brought mathematics to science. For the first time, he showed that mathematics can describe physical things in the universe, whether it is the heavenly bodies or molecules moving around in the cell. For some reason, mathematics is very powerful in being able to describe nature, and Newton was the first person to demonstrate that.

4. What in your opinion is the single most important scientific breakthrough, and why?
Again I’m going to go with Newton’s three laws of motion for the same reasons. I like Newton.

5. What are you major interests outside the lab?
I have lots of interests. Family is really important to me, so is music. When I was younger, I had a difficult time deciding if my career path was going to be music or science. I now spend about four hours a week playing the pipe organ. The organ and classical music are of huge interest to me and they are almost equal to my passion for science.

6. Why science?
Science is wonderful. I loved physics as a kid. My best friends were physics students in secondary school and we loved building things after school, such as magnetic bottles to hold plasmas. Science is a wonderful way of looking at the world because it quickly takes us to the limit of the “how” questions and bumps us up against the ”why” questions. Physics in particular is great because it takes us to that limit where we then have to move into poetry and philosophy, and I love being at that interface.

7. Why SickKids?
I spent the first 17 years of my academic career at the University of Calgary and I loved it there. By 2001, I thought to myself: “I need a push. If my research is going to continue to develop, I need to be in a really intense research environment like University Avenue in Toronto.”

SickKids is a fabulous place because there’s wonderful basic or fundamental research that goes on here and there’s exciting clinical research as well. SickKids is a wonderful place because it does both well, with children’s health, in particular, as the ultimate focus.  

8. What is the most controversial question in your field right now?
There are lots of big questions. Again, it’s really surprising that in spite of how important DNA is, we still don’t know how it is packed into the cell nucleus. There are many models and controversies and conflicting views on how this occurs. I hope our microscope will be able to sort this out.

In the PML body world, some people think that they don’t do anything, or maybe just serve as storage sites. But I think they are fundamental structures that actively bring sets of genes together.

9. What are you reading right now?
I’ve become very concerned about our society’s “war against nature”. Our consumption and wasteful living practices are not sustainable and are causing all kinds of problems in both the developed and developing worlds. I’m doing a lot of reading about these stresses and the likely consequences of the way we are living.

10. If you could give one piece of advice to someone considering a research career, what would it be?
If you have curiosity and you wake up in the morning with exciting questions in your head about how things work, then go into research! It’s an amazing time to do fundamental or clinical research because of the huge strides that are now possible. Go for it!

11. What does The Research and Learning Tower mean to you?  
I was just at the Research Institute Retreat and I saw so many people that I used to see all time when our lab was in the Elm wing on the main campus. It’s terrible that I haven’t seen these people since last year’s retreat. We used to have great discussions and meeting once a year is not enough. The tower will allow us to come together again and interact in ways that we need to in order for ideas to grow and develop.

November 2010

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