Friday, August 28, 2020

Interns!

While my problems pale in comparison to what is currently going in the world, this has been a rather tough week. Two papers and a grant were rejected all within 5 days of one another. It is probably a good thing that Seoul Pub is closed. I realize that these set backs can be an opportunity to make the papers and the grant stronger. I'm also not that I am that mature and really want to complain to anyone within earshot. So I have been thinking of the mentors who guided me, trying to recall how they responded to disappointments. This makes what happened today even more remarkable.
I have written before about my internship at Eli Lilly & Co. while I was in college (https://www.blogger.com/blog/post/edit/2237994772082994999/9119638604504809769). That experience changed my life, and as a result, I have several interns in the lab. I do not care what your background is. If you want to be in the lab and learn, it is important to me to give you every opportunity to succeed. I also find yelling, "Intern!" to be extremely therapeutic. Try it. It's rather surprising.
Employee's children going to college could get a summer job at Lilly's which is how I started. I was very lucky to get placed in a research lab. Having a new student for only three months with very little lab experience is not exactly a recipe for success. Indeed, I often heard the phrase, "Summer help, some are not." I was often in the 'not' category. I will always remember the very first thing I was asked to do, serial dilutions. I remember it because I couldn't do it. I was so embarrassed. Nothing like lowering expectations on your first day. Since that time, I have seen labs release people for such a mistake. This leads me to the second reason I remember that moment. Instead of chastising me, he just asked if I was having trouble. When I nodded, he simply said, "Let me show you."
Fortunately, my time in that lab spanned nearly three years. I was even given a project that led to my first publication which enabled me to go to grad school. (WARNING! Since this is a public blog, I should point out now that there is about to be a lot of sexy talk. If that kind of thing offends you, you might want to skip the next paragraph.)
Penicillin is an antibiotic that has a four ring structure. Some bacteria can recognize that four ring structure and eliminate it resulting in antibiotic resistance. Cephalosporin is an antibiotic with an expanded ring structure that can be used to treat penicillin-resistant bacteria (excuse me, I need a cigarette). Since Lilly's is a pharmaceutical company, they were studying how cephalosporin is produced. In some organisms the four ring structure is expanded and hydroxylated by a single enzyme called expandase/hydroxylase. In other organisms that chemical process is done by two separate enzymes, one called expandase and the other hydroxylase.
I was working on hydroxylase while the guy who showed me how to do serial dilutions was working on expandase (or technically, recombinant DAOCS). We were using a technique called HPLC which enabled us to separate the expanded ring compound made by the enzyme expandase from the expanded ring/hydroxylated compound made by hydroxylase. One day my colleague's machine breaks down, so he ran his assays on my machine.
I should point out that HPLC is a very unforgiving technique. If your experimental technique is poor, you will see it in the different amounts of compound coming off the HPLC. I know this from experience, as my pipetting skills were rather poor. So I really wanted see how good my colleague's skill was when I saw a small but real amount of hydroxylase compound coming off the HPLC. There should only have been the expandase compound present, but it turns out that all of these enzymes could catalyze both the expandase and hydroxylase steps with differing degrees of efficiency. No one had ever seen this before. Even though it wasn't my experiment, it was the first time I felt I had contributed to the lab.

Why do I tell this story now? Because today I got a notification that my hydroxylase paper published 29 years ago was referenced (https://dx.doi.org/10.1021/acs.inorgchem.0c01211). What did they say? "In fact, recombinant DAOCS in S. clavuligerus showed an extremely low level of DACS hydroxylation activity..." They referenced that experiment! How cool is that? I'm guessing I'm not the only one that could use a cigarette right now.
All kidding aside, this made me feel really good especially at a time when I could use some inspiration. You never know what's going to matter or when or by whom, so you must continue to fight the good fight. Which reminds me...

"Interns!"

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