Dr. Steven Griffiths Monthly Column, published in the Times & Transcript

Microbiology opens up breathtaking universes

Tuesday March 18, 2008

My first brush with microbiology might have been an attempt to examine an entire snail between microscope slides on Tim's garden wall. Tim will cheerfully remind you of this atrocity 35 years later (although he might insist it happened more recently).

Soon after though, with a scope of my own and greater appreciation for sample preparation, I discovered that breathtaking new universes existed in any smear of pond slop. I filled exercise books with sketches of creatures that looked like translucent armored cars or bizarre vacuum cleaners that looped their way along exquisitely detailed emerald tubes. I was hooked.

Nonetheless, it was a bit of a crushing blow later on to learn in school that the science of life was based on atrociously dull, stick-figure symbols. I was not fond of math and I only tolerated chemistry by proxy. But it seemed as if biology would boil down to this dreadful rote-learning, similar to the repetitive chanting of foreign verb conjugations, during my earlier years at Torquay Boy's Grammar School in England.

Fortunately, before it was too late, Mr. Veale appeared.

Beyond being a superb educator, authentic and authoritative with an effortless command over any sociopathic rabble, he also broadened the biology curriculum further than what was required.

Without this gifted teacher, I may well have gone in another direction or worse. He even got me an interview at Oxford University. Unfortunately I was brought down to earth on that occasion by a stuffed weasel. But that's another story. Among many other aspects of his preeminent influence, Mr. Veale introduced us to scientific literature outside of the stodgy textbooks.

Thirty years ago this month in fact, there appeared an article in a magazine called the Scientific American. (How Cells Make ATP Hincle P.C. and R.E. McCarty (1978) Scientific American March p104-123)

As I mentioned earlier, the barren cycles of biochemistry left me dazed. In this article though, equations and arrows were transformed into three dimensions, blossoming into my consciousness like a comic book landscape.

As archaic as the illustrations might look today, at the time they were spellbinding: amazing cogs and turnstiles, passing things back forward, creating concentration gradients like the rising tide is caught to generate hydroelectricity. All of this machinery operated in tiny structures inside our cells, structures that had once been living independently as primitive bacteria. It was astounding. There was yet another universe beyond the tiny creatures that had attracted me to this kind of stuff in the first place. A genuine interest had been reignited, something far preferable than something I felt that I needed to be good at.

And so it was off to university to major in cell biology where regular beatings from math and chemistry were unavoidable and as a result, I barely scraped by. Fortunately, I was saved in the final year by the opportunity of fiddling around in the water with microscopic things again and ended up acing a project on fish disease. Yes, that's right: fish disease. After graduating in the mid 80s, there was no better place in the world to rescue salmon than Canada. My supervisor had studied at a place I had never heard of called Fredericton. He passed me along to his ex-boss and a post graduate degree followed at UNB. As luck would have it after graduation I was directly adsorbed into an institution not five yards from the university gates, to perform similar research and development for the government and the now burgeoning aquaculture industry.

I'm not the smartest bloke on the street but, generally speaking, if you really enjoy something then you're going to get better at it, no matter what your skill level, and good things are likely to happen. I ended up leading a group that developed several important vaccines and identified some mystery diseases that had otherwise foiled veterinary colleges.

Meanwhile back in the amazing world of protein rotors, gears and switches, things were moving fast. New lab techniques were enabling the analysis of massive numbers of proteins simultaneously to determine which changes among them might indicate that something was wrong; which bits could be targeted to make things better, to signal adverse environmental changes, or to generally illuminate whatever your interest in the science of life might be.

The new approaches and technology were referred to under the awful umbrella term "proteomics." During my last months in Fredericton I was attempting to get such a proteomics facility set up so that Atlantic scientists would have access to this cutting edge technology. It was at the Beauséjour Medical Research Institute that, for the first time in my professional career, I met someone who immediately got what I was talking about and shared the vision of the new approaches and the abilities to shake proteins out of the piñata to see what was going on and, where necessary and possible, how to modify them. That someone else shared this excitement was reassuring: not only was he a PhD in molecular biology but a practicing MD. It was my future boss Dr. Rodney Ouellette. Three weeks later he brought me on board. And here we are today as the Atlantic Cancer Research Institute in Moncton.

Despite all the years that have gone by, I am still enthralled by the microscopic world, just as I was as a small child. These days though, rather than be bowled over at some new and tiny combination of claws, fangs and legs, I get gob-smacked by revelations in the myriad of ways in which proteins are modified or interact with one another.

At ACRI one of our goals is to find out which of these proteins misbehave for a variety of possible reasons.

Such rogue proteins might no longer require a nudge from another to pass along an important message for cell division, but instead do it all the time without any prompting. Alternatively, when some other distorted proteins get nudged, the message isn't passed along at all and the normal sequence of checks and balances are ignored. The quicker we detect these proteins, the easier it will be to treat the cancers they cause. Another line of study centers on the known precept that misbehaving proteins can be sufficiently different from normal to be recognized by our immune system; rather like the virus proteins in a flu vaccine. Unfortunately, this is not always the case. My job is to develop methods that allow the patient's body to identify such differences more clearly and throw the buggers out.

In this column, "The Science of Life" I'm going to try and share some of my enthusiasm for the things that make us tick and the reasons why everything doesn't always go like clockwork. In the next column we'll take a closer look at the cogs of life, the proteins, and the factories in which they operate.

n Dr. Steve Griffiths is a researcher at the Atlantic Cancer Research Institute in Moncton. His column, the Science of Life, appears in this section on the third Tuesday of each month.

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(Published in Times & Transcript)