Lab revelations

I am going to talk about some of my own work today. My sabbatical is going well, but I can sense that the Winter semester is around the corner. As of January 1 I am back to my regular job at the Chemistry Department. Thus far, my experience at SGC (http://www.sgc.utoronto.ca/sgc-webpages/sgc-toronto.php) has been a blessing. I have learned a lot of new things about structural biology. More importantly, some of my students are now trained in protein chemistry and crystallization (thanks to Elena). I also have to thank my good friend Al Edwards, who was at the beginning of it all. I refer to his role in the foundation of SGC together with Cheryl Arrowsmith as well as to his shaping of my interests in protein crystallography. Below is Al, by the way, along with a drawing he made at Starbucks some 6 years ago when we discussed standard conditions for crystal growth by slow diffusion. It all looks deceptively simple, but the devil is in the details. The trick is to get into the right “zone” that is conducive to crystal growth. Passing that zone is easy and it is all about conditions, conditions, and conditions (to paraphrase the real estate dictum).

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As far as me doing lab work, here is the man lesson thus far: it is really good for an academic to go back and get calibrated in the lab from time to time. Besides its educational value, this experience reminds me about how rarely things actually work in research. Ironically, this is something that is special about research experience because we feel good when things do work. At the same time, if one’s heart is not 100% in research, failures can be a real drag. I have always enjoyed the challenge, so it is ok for me. But I will tell you this: if you are a professor and are sitting in your ivory tower overlooking a range of projects, it is easy to forget that each of your graduate students is in fact focusing on a specific and often narrow area of research. There is a significant ramification here: it is more difficult to get frustrated in the ivory tower. If there are no results in a particular project, there is always another, parallel, area that does generate results. In time, things fluctuate in terms of success between the areas. It certainly is tougher to be in the students’ shoes. It just ain’t the same when your job is fixed to one problem. Now… there is a practical and obvious lesson here for the students: always (yes, always) balance several different projects on your plate. In this case, the chance of getting discouraged about lack of results will be smaller.

For example, we evaluated a battery of new conditions aimed at understanding macrocycles and their folding in the crystalline state. I hope we’ll get some new hits but things have been difficult thus far. I set up 480 experiments and one of them worked, giving me crystals that unfortunately did not diffract today. But that’s ok – a couple of hours later I went back to my chemistry lab and talked to Piera, Adam, Shinya, Frank, and Victoria about their plans in boron chemistry. See: there was a total “switch”. We failed with our crystals earlier in the day, yet I got rejuvenated after a switch to something totally different. We bounced ideas and things are looking up… It’s all about balance.

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