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This week we move on to proteins and enzymes, which means time spent with some of my favorite enzymes, protein kinases. Proteins kinases are enzymes that attach phosphate groups to other proteins. Considering the size of a typical protein, this addition of a few atoms (one phosphorous and three oxygens) does not seem like a big deal. Sort of like the little sprig of mint dressing an amazing entree at a nice restaurant. But that is not the case.. the addition of a little phosphate can have drastic consequences on the structure, and consequently, the function, of a protein molecule. An enzyme modified by a phosphorylation event may change one hundredfold or more in its activity, upward or downward, depending on what the phosphate does to the shape of the protein. The power of the phosphate resides in that one little negative charge that it carries. A few extra electrons strategically placed can change everything.

Many, many proteins are regulated by phosphorylation. Not only can the activity be affected, but also the stability, localization, substrate specificity and more. And it is not uncommon for one protein kinase to have its activity regulated by another protein kinase, which in turn is regulated by yet another protein kinase, and so on and so on and so on.

The phosphate groups are removed by opposing enzymes called protein phosphatases. We do not know nearly as much about these enzymes. I heard a fascinating seminar about an attempt to design protein phosphatase inhibitors, including inhibitors for my all time favorite phosphatase (Cdc25A – long story). There is some promise that these inhibitors might help treat a host of problems, from cardiovascular disease to cancer.

When one spends too much time thinking about kinases, phosphatases and phosphate groups, one sometimes develops the mindset that phosphorylation rules the world, or at least, rules the cell, from which all living systems are made.

Phosphorylation is a very digital event. A given amino acid in a protein is either phosphorylated or it is not. The phosphate confers a single negative charge. The subtleties and gradations arise as they might in any digital system. In a given protein, there may be multiple phosphorylation sites, some of which are occupied and some which are not in any given condition. This allows for an enzymes to be active to varying degree rather than just “on” or “off”. Or in a population of many enzyme molecules, not all may be phosphorylated at a specific site if the kinase activity is low. There are stochastic elements to be sure.

I realize this is an incredibly reductionist view and one about which I am not particularly proud, but if I can convince myself that digital devices are not scarier than the cells I know and love, then maybe I won’t be so afraid of that other cell in my life – the one called iPhone that my 8 year old daughter has to teach me how to operate.

This week my class will be creating models of the building blocks of cells using foods that contain those building blocks. A phospholipid bilayer made out of french fries and donuts. Glycogen made out of angel hair pasta. You get the picture. Almost every cell and molecular biologist I know likes to cook, and I am no exception. I have often wondered why. So much of our best work is microscopic or even submicroscopic. Maybe we get a thrill at coming home from the lab and making something we can actually see. And so much of our work (especially the molecular processes) has to be so precise. 1 microliter of this, 2 microliters of that. Deviate from the protocol (recipe) just a little and you’ve wasted $1500 in reagents (ingredients) and may have set your dissertation back several months. After a day like that, it can be incredibly cathartic to leave those measuring spoons in the drawer, ignore the Joy of Cooking, and start throwing things in the pan. I may be a scientist but there is an artist inside dying to crack some eggs.

Don’t stifle my creativity. Except, of course, when it comes to meringues. Then I’m smuggling my analytical balance and thermometer that reads to .001 degrees home from the lab in the hopes of getting it just right this time.

One of the main topics for class this week is the use of model organisms for research in cell and molecular biology. How many models do we need? Which is best? Hopefully, students will reflect carefully on these subjects as they work through the assignments. However, we won’t spend very much time on the topic that haunts me – especially this week: almost all of the model organisms will die (we use the euphemism “be sacrificed”) during or at the conclusion of the experiment. This is a significant moral choice in the life of a scientist working with animals.

A week ago today, I had to say goodbye to  my best friend, my 5-year old catahoula, Comet. Comet finally succumbed to the side effects of Rocky Mountain Spotted Fever and the medicine used to treat it, after a valiant two-year battle. Comet was actually “euthanized”, another technical term for the fact that I made the choice for the veterinarian to take his life, in this case, because I couldn’t bear to see his suffering. Comet was more than a pet. He was a member of the family.

Yet I sit here in my office with minimal concern for the frog that sits in the bucket next to me. I have conducted research with this species for about 15 years now, and in the course of that time, I have personally “sacrificed” dozens of frogs, and approved the “sacrifice” of many more. This has not been without feeling. I really like frogs, and may even love them. I worry about their health, I feed them live crickets and worms instead of just the lousy frog chow, and when no one else is in the lab, I sometimes talk to them. Yet, my moral compass has  guided me to a belief that the research that I have conducted and the quality of training I have offered my students has justified the end of many little amphibian lives. I have not cured cancer by any means, but I may have helped. And I have not solved the mysteries of amphibian decline, but I may have added to the dialog about why and how.

I respect people who do not support research with animals, and yet I do not understand how they can live their lives consistently, without benefiting from that research.  I do not respect anyone who is cruel to animals.

In animal research, we are taught the 3 R’s, reduce, replace and revise (sort of like reduce, reuse, recycle). The goal is to minimize the use of animals and any suffering they might incur. The Japanese have added a fourth R: respect. Japanese scientists build memorials to the animals they have used for research and even hold remembrance services for them. I like that.