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About the Institute

Profile of Charles Deber

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Dr. Charles Deber

Dr. Charles Deber, PhD, FRSC

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

1. Where are you from? /Where did you study?
I was born and raised in Brooklyn, New York, and lived in one apartment building for over 20 years. In one direction was Manhattan and all of the exciting spots like Broadway, Madison Square Garden and the Empire State Building, and in the other direction was the beach, Coney Island, the boardwalk, home of Nathan’s famous hotdogs.

I did my undergraduate degree at the Polytechnic Institute of Brooklyn, which is now called the Polytechnic Institute of New York University (NYU-Poly). I was fortunate enough to then go to the Massachusetts Institute of Technology (MIT) in Boston to pursue my PhD. I remained in Boston for post-doctoral studies at Harvard Medical School. I spent a year at the Enzyme Institute, University of Wisconsin, Madison, before coming to SickKids.

2. What are you researching right now?
We are researching the structures of proteins that are embedded in the membranes of cells.

If you take a red or white blood cell, or single-cell bacteria, and look at what separates the inside of the cell – where the biological reactions take place – from the outside world, you will encounter the cell membrane. In effect, the cell is a compartment separated from everything else by the membrane that is made out of a fatty substance that cannot be easily penetrated by water. In that case, however, the cell or the bacterium could not exist without a means to get nutrients in, wastes out, and without receiving signals from the outside, such as when to reproduce, for example. In order to transmit nutrients and signals, nature has embedded into these membranes a highly specialized group of proteins. The main function of these membrane proteins is to selectively and specifically send nutrients into the cell and send various signals to instigate growth or reproduction of the cell.

Each membrane protein molecule has a particular structure and amino acid composition that dictates its biological function. My research team is trying to understand how the membrane proteins are inserted into the membrane, and how they fold into the correct three-dimensional structure that works and carries out the intended function. From a medical perspective, it turns out that many human diseases, such as cystic fibrosis, arise from mutations in the genes that code for these proteins, and the genetic ‘mistakes’ get translated into mutations in the proteins when then become defective in function. For example, in CF, a protein called CFTR helps to regulate the sodium chloride (salt) balance in and out of your cells; if this doesn’t work correctly, you can end up with thick mucus in your lungs. Through our research we are comparing the normal proteins with mutated proteins so we can identify the differences. This is the first step in the process toward developing treatments for disease, as you need to understand the nature of a defect before you can develop something to correct it.

While our research is largely basic science, the work that we do helps to understand relationships between molecular structure and function. This is very important for pharmaceutical research as a large part of the work in this area is focused on developing therapeutics that target membrane proteins.

3. Who is your all-time favourite scientist, and why?
Every once in a lifetime you meet someone who has a transforming effect on you, sees something in you and pushes you in the right direction. Murray Goodman was that person for me. I met Dr. Murray Goodman while I was an undergraduate at Brooklyn Poly. He accepted me into his lab for my Bachelor’s thesis and this work inspired me to take the scientific path that I chose.

One of the most important things I learned from Murray is that becoming a scientist involves more than just the research and experiments. To run a lab effectively, there are several other elements to manage – there is a people side, a political and diplomatic side, and very importantly, a communications side: if you don’t publish your work, and if you don’t go to conferences to speak about it, nobody will know what you’ve accomplished. Dr. Goodman had all of these qualitities and was able to understand people, understand their different strengths, and knew how to treat each person differently. Murray became a mentor and helped guide me in my early career.

Later on, Murray moved to establish a lab at the University of California, San Diego. After a number of years in Toronto getting my own independent research career established, I joined Murray again for a few months on a sabbatical in his lab in California.

4. What in your opinion is the single most important scientific breakthrough, and why?
In considering the answer to this important question, let me first recount an anecdote. In the early 1960s there was a monologue (on vinyl!) by Mel Brooks and Carl Reiner entitled “The 2,000 Year Old Man”. In this piece, Reiner played a reporter who was interviewing Brooks - a man who purportedly had lived for 2,000 years. The reporter asks the 2,000 year old man what in his opinion was the most important scientific discovery mankind ever made. The old man responds by suggesting that saran wrap was the greatest innovation. In response to the reporter’s surprise with this answer, the old man proceeds to describe many of the useful applications and features of saran wrap, such as that you can wrap sandwiches in it, and that it’s waterproof, etc. When the reporter provides other great examples – such as splitting the atom, or inventions such as the telephone or the automobile - the old man simply agrees, remarking, “Sure, those were also good.”

My point is that it is hard to choose to just one thing. What I consider to be at least one of the most important breakthroughs in science is the understanding that human disease is caused by microorganisms – things we can’t see with the naked eye. Imagine all of those thousands of years that went by and people would get sick and populations would be devastated by plagues – all caused apparently by some invisible force. People didn’t really know how to explain this. Then slowly but surely through the invention of the microscope and the work of great scientists like Louis Pasteur who developed early vaccinations, the understanding came about that many human afflictions are caused by bacteria or viruses. That in turn opened up huge areas of research that have eventually allowed us to address the question, ‘what are we going to do about it?’ Now we have new technologies to see what is small and floating around us and inside us everywhere, and we have a greater understanding of our world, and are learning more and more all the time about how to combat these organisms. And perhaps not coincidentally, when we look at the molecular components of these microorganisms, we see that they live and proliferate using many of the very same membrane proteins of interest to our own lab.

5. What are your major interests outside the lab?
I have a major hobby which is constructing crossword puzzles. It started off as a fun activity, applying my scientific mind to words. One day I decided to make a serious attempt and used the occasion of Canada going onto the metric system to create a full puzzle. I submitted this first attempt to the New York Times. It was rejected, but the editor included some very helpful tips and encouraged me to continue trying – which I did on and off. Finally, about five years later, I had one of my puzzles published in a major puzzle magazine. I eventually got one published in the Sunday New York Times and today I have had about 35 puzzles published in the Times, with a byline. I only have time to do three or four a year, but it is a very refreshing and rewarding hobby that takes my mind to new places.

Piano playing is another great hobby for me. As a child, I took piano lessons and even went on to play a recital at the Julliard School of Music in Manhattan. Subsequently, I have learned to play by ear, and just like with science, it is the logic of the patterns in the music that attracts me.

I also watch a lot of hockey, and spend some time learning about and enjoying fine wines.

6. Why science?
When I think back as to how young people decided on what career to pursue, it was different back then. There was no internet, no websites.There was barely any scope for introspection. Decision-making had more to do with chance interactions and influencers, like my experience with Murray Goodman. The only overiding thing in that day was the sputnik era. The US and Soviet Union were in a perceived science contest. As a result, I believe that many of the academic advisors funneled students that had any aptitude for chemistry, math, biology and physics into a science-focused curriculum.

I eventually ended up in chemistry and while I was relatively successful, it only slowly began to creep up on me that this was something I actually enjoyed. Eventually this evolved into the “eureka!” kind of enthusiasm that a scientist has for his or her work and the excitement of creating new knowledge. So if you are fortunate enough to survive the system, get the grants, attract good students and post-docs, establish a lab, and have the intellectual freedom to explore and be aware of the evolving questions of the day in your field, it really is a tremendously rewarding career.

7. Why SickKids?
When you first join a new place, you don’t know what it will be like, how long you will stay, if you are going to fit in. My wife Raisa (who’s from Toronto) and I came here because we were both seeking jobs in academia and knew the University of Toronto and the surrounding community to be an excellent research environment.

But something happened that I did not anticipate and I think is really unique to SickKids. As scientists here at SickKids, we are surrounded by a clinical setting, and you can’t help but see the doctors, the nurses, the families, and most importantly the children, dealing with illnesses. As a scientist I am working on proteins that are related to the genetic diseases of children and I found myself becoming inspired by what surrounded me. It drove me to make my work matter for these kids. It began to sink in that there is a mission or a practical side to even the most basic science – and little by little I moved my work and interests into the more disease-focused areas such as cystic fibrosis, cancer and multiple sclerosis. I am now able to study the basic ‘stuff’ because nature only has a handful of fundamental interactions among proteins and membranes; it turns out that a wide variety of human diseases are actually caused by similar types of protein defects. I am happy to be able to apply my work directly to addressing the challenges we face in understanding and developing therapeutics to address these diseases.

SickKids is also a unique institution in that it allows us as scientists to have the freedom to pursue our research interests without an excess of oversight. I am very appreciative of the liberal environment in which we do our research.

8. What is the most controversial question in your field right now?
There isn’t a single question in my field that we universally face and debate at conferences. I think the one thing I could highlight here is the distinction between scientists who study biology of intact cells and those who study the biochemistry of individual proteins. In biology of course you have the proteins in your cells, doing what they are supposed to be doing, in their natural environments, sending in the glucose, balancing the salt content, signaling the cell to reproduce, etc. But biochemists want to know: how do they actually perform these complex functions? Since the membrane proteins we study in my lab are insoluble in water, they are extremely difficult to extract from membranes, and they cannot easily be maintained in their natural state. Therefore, in order for the biochemists to study these proteins, they have to create what are essentially artificial states. This artificialness uses other substances, such as soap-like detergents that mimic the natural state of the proteins, but certainly aren’t exact. There is therefore the potential that we are losing key information about the protein.

In my field, the ‘truth’ is in between, and while the truth needs to be known, we don’t yet have technologies that can allow us to study these proteins in a natural state, but we can still study and learn from the methodology we have today and can get closer to the truth. This is what I would call a kind of ‘macro’ Heisenberg uncertainty principle. This principle deals with the study of very, very small things. It was found that the very act of measuring their properties itself affected the properties of what was being measured. In our case, we similarly have to change to the environment of the protein in order to study it in the absence of the cell. Our current challenge is to develop methods that mimic as closely as possible the original the native states.

9. What are you reading right now?
I am not known to be a heavy reader but I do enjoy reading a good book from time to time. Recently I read the book, Bellwether, by Connie Willis. The book used chaos theory to discuss how fads start. The story was a great metaphor on leadership, using partly science fiction and partly humour.

10. If you could give one piece of advice to someone considering a research career, what would it be?
I believe that everyone in life wants the same things – they want to feel good, look good, have satisfying relationships with people – but when thinking of a career, each of us has different strengths. Therefore, you first need to discover what you are good at.

If you are in high school, or doing your undergraduate studies in university, and are considering becoming a scientist, you need to ask yourself not only whether you getting good marks in your science and math subjects, but do you feel you can see into the lab experiments in your courses to understand the fundamental principles and conceptual underpinnings of the experiments?

If you are at the stage in your career path where you have achieved the first hurdles of your science subjects in school, and you are looking at graduate (Master’s or PhD) work, you need to ‘do the math’ at that point. You have already spent several years in school and with a scientific path you are facing many more years without an actual job. You have to look at this reality and decide not only that you love science but that you also will enjoy the journey. You will find that you are among people with a common thread, who are all there for the same reasons as you. They love science and have an aptitude for it and they are probably even a little bit nerdy. And be aware that don’t enter science with an expectation of a huge salary windfall or a quick promotion. It is a world of gradual process, long days of lab work, a long career ladder. You need to have a personality that is patient, that can deal with rejection (like grant or manuscripts turned down!), and be able to look past those negatives as minor compared to the excitement of discovering new things. You will have the opportunity to travel all over the world and share your ideas and meet colleagues with similar interests. It’s a great life, at some stages a bit slow, but in the longer range, incredibly rewarding.

August 2010

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