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About the Institute

Profile of Lynne Howell

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Dr. Lynne Howell, PhD

By: Mackenzie Hill-Strathy

Dr. Lynne Howell, PhD

  • Associate Chief, Reseach Integration and Communication
  • Program Head and Senior Scientist, Molecular Medicine
  • Professor, Department of Biochemistry, University of Toronto

1. Where are you from?/Where did you study?
I am originally from Britain, and completed my undergraduate degree in Biophysics at the University of Leeds in northern England. I then went on to do my PhD at the University of London in Crystallography, and postdoctoral studies in Boston with Gregory Petsko at the Massachusetts Institute of Technology. After that I moved back across the Atlantic for a short period of time to the Institut Pasteur in Paris. I spent my first year there as a post-doctoral fellow and then a year as a staff scientist. I moved back to North America and joined SickKids in 1991; I have been here ever since.

2. What are you researching right now?
We are interested in two processes that are part of the life cycle of a biofilm.

Bacteria can exist in two forms: free swimming (planktonic), or attached to a surface in a biofilm. In a biofilm – the surface attached bacteria produce a matrix that protects them from external forces such as antibiotics. An example of a biofilm is the bacteria that attach to the lung of a cystic fibrosis patient. These bacteria are protected from the host immune system, which is actually trying to get rid of them. Bacteria prefer this method of growth, as 60-80 per cent of chronic infections are a consequence of bacteria growing in this mode. What we are trying to do is examine how bacteria attach to these surfaces. In my collaborative work with Dr. Lori Burrows at McMaster University, we are examining the attachment appendage that bacteria have, called a type-4 pilus. It works like a fishing rod attaching the bacteria surface and reeling them in. We are trying to understand how the pilus is assembled and how this machine works to extend and retract this rod-like structure.

The second part of what we do is looking at how the matrix is made. The matrix can be made up of a number of different polymers: proteins, DNA and carbohydrates. We are specifically interested in the carbohydrate polymers that make up the bulk of the biofilm matrices. There are a number of different polymers that can be produced; some bacteria can even produce different polymers at different points in time and in different environments. We are interested in how the polymer is produced, with the long-term goal of trying to understand how the protein machinery works. Our goal is to figure out ways to either stop the production of the polymer or to degrade the polymer once the biofilm has formed, releasing the bacteria back into their planktonic form. In the matrix form, bacteria are 1000 times plus more resistant to antibiotics. When we release the bacteria back into their planktonic form, they should be more susceptible to our current antibiotics.

3. Who is your all-time favourite scientist and why?
I’d have to say Marie Curie or Dorothy Crowfoot Hodgkin – both women who were pioneers in their field and are great role models.

Marie Curie has the distinction of being the first woman to win a Nobel Prize. She has actually won two, in two different fields, and more importantly in two different branches of science. She is still the only person to do so. She first won in 1903 in physics for her work on radiation with her husband Pierre Curie. She won the second in chemistry in 1911 for her discovery and characterization of elements radium and polonium. One of the reasons I like her is that she had a number of quotes attributed to her, that are equally valid today as they were 100 years ago when she wrote them. One of my favourites is: “one never notices what has been done; one can only see what remains to be done.” This is a nice reminder that you need to look back to see how far you’ve come, it puts everything into perspective.

The second of the two women is Dorothy Crowfoot Hodgkin, who I actually had the pleasure of meeting. In the 1930’s she became a pioneer in X-ray crystallographic analysis and determining the three-dimensional structures of chemical matter. She won a Nobel Prize in 1964 for the work she did determining the structures of penicillin and Vitamin B-12. She was also responsible for determining the structure of insulin. During their lifetimes both these women had an extremely tough time being a woman in science, and the fact that they succeeded and accomplished so much is inspirational to me.

4. What in your opinion is the most important scientific breakthrough and why?
In my field there are two people with two important breakthroughs. In 1895, Wilhelm Conrad Röntgen discovered X-rays. There is a famous story about Röntgen. He was doing a set of experiments in the lab and put his wife’s hand with her wedding ring in front of a beam of light, with a film behind it, thereby taking the very first X-ray of bones and soft tissue. The consequence of his discovery immediately had applications in the medical field but also has relevance to the study of chemical matter.

The second important breakthrough was Max von Laue’s discovery of the diffraction of X-rays by crystals, which won him the Nobel Prize in 1914. This was really the birth of the whole subject of crystallography. From the point of view of the work I do, without these two discoveries, there wouldn’t be a field of structural biology. This year, in 2014, we are celebrating the hundredth anniversary of Max von Laue’s discovery and UNESCO has declared this the International Year of Crystallography. This also celebrates roughly the 400th anniversary of the first observation of ice crystals, by Kepler in 1611. These discoveries opened up a whole new scientific field – the structural characterization of chemical matter, and made possible the structural determination of over 100,000 protein structures to date.

5. What are your major interests outside the lab?
Besides hanging out and travelling with my husband, in the summer I crew on a sailboat. I am taking part in a series of races over the summer that takes me out on the water on Wednesday evenings in the Toronto harbour. In the winter, I love to curl and belong to a club and curl twice a week in house leagues. Other than that, I try to stay fit by running three to four times a week!

6. Why science?
I’m very inquisitive and like to know how things work. When I was young my dad was a science education officer for an organization called the British Council. When I was about eight or nine, I remember helping him build models of dodecahedrons, tetrahedrons and other symmetrical shapes – my job being to help paint and stick the pieces together. This sparked an interest in how things fit together, in the symmetry of these molecules and how they functioned. In the field I ended up in, symmetry underlines the whole principal of what we do. So I guess it was being inquisitive, always loving science, and having a dad who helped to feed my curiosity.

7. Why SickKids?
My decision to work at SickKids was entirely the consequence of the individual who was the chair of Biochemistry at the time, Dr. Amu Sarkar. When I was recruited in 1991, there was no structural biology program in Toronto. There was an advertisement in Science and Nature for eight positions across three institutions, all on the same page. The jobs were at the University of Toronto, the Ontario Cancer Institute and here, at SickKids. I was looking to return to North America from Europe, but I didn’t really know much about Toronto at the time. I actually applied to positions at both OCI and SickKids, and was lucky enough to be offered jobs at both. Dr. Sarkar really went out of his way, above and beyond, to really showcase what SickKids is about: how collegial we are, how dynamic the place is. He was a wonderful mentor as I established my lab. So why SickKids? It’s him. He is responsible for bending over backwards to ensure that I understood the differences between the two institutions, and the merits and advantages of this one.

8. What is the most controversial question in your field right now?
This may not necessarily be most controversial, but it is the most important. Some of the most pressing questions in my field are about how matrices are formed, what governs their maintenance and more importantly how they break apart and cause acute infection. This is important to understand because when embedded in the matrix, the bacteria are well protected, they may receive sub-inhibitory concentrations of antibiotics and will eventually adapt to these antibiotics. This increases the problem of antibiotic resistance and our ability to combat acute infection.

There haven’t been too many new antibiotics on the market in the past 10-20 years, and as the WHO documented this past April, we are on the precipice of a post-antibiotic era. Soon there will be bacteria for which we have no treatment. This is scary because diseases that are treatable now will become impossible to treat in the future. Figuring out how the biofilm matrix is made will be critical in helping our fight against antibiotic resistance and the lack of new antibiotics.

9. What are you reading right now?
I’m a member of a book club, so I always have something on the go. However, during the summer we take to break, so right now I am indulging myself in one of my favourite genres – fantasy, which doesn’t go over so well with some of the ladies in the book club. I’m a huge Tolkien fan! Who isn’t? When I was little my dad read us The Hobbit, and I have been a huge fan ever since. At the moment I am reading The Wise Man’s Fear, the second book of Patrick Rothfuss’ trilogy, The King Killer Chronicle. It is a classic case of good against evil, pure escapism, which is exactly what one needs to relax after a long day at work!

10. If you could give one piece of advice to someone considering a research career, what would it be?
What a successful research career really comes down to is that you have to be prepared and willing to try new things, to be equipped to explore different avenues. You have to think outside the box. Always keep in the back of your mind that if you get the result you are expecting to get when you do an experiment, that maybe you weren’t doing the right experiment. Its nice to design experiments and get a result that is unexpected. It is important to keep an open mind and read prodigiously as much of the literature as you can. This way when unexpected results arise, you have enough background knowledge to go “aha!” I know why that is.

11.What does the SickKids' Peter Gilgan Centre for Research and Learning (PGCRL) mean to you?
As a program head it is a wonderful opportunity to bring people in the program together for the first time. When we were in the old building, there was a core of people that were together, but a large number of us were spread out across a large footprint. The Peter Gilgan Centre for Research and Learning (PGCRL), offers the opportunity for us to come together as a program, and we have already built some cohesion as a consequence. There is a lot of synergy among members of the program, and this building helps to further surge that synergy. On a more personal level, I am excited by the opportunity to meet with other scientists in a social environment. I can go downstairs and have a coffee with a cell biologist. The ability to bump into someone that you wouldn’t have met otherwise is really neat, and I hope this building allows for further opportunities to interact on a social basis. After all, it is from those social occasions that collaboration starts.

November 2014

Scientific profile