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How to Choose a Protein: A Comprehensive Guide For Future Biology Graduate Students (Or A Dating Guide For The Rest Of Us)

  Hannah Foster /   February 26, 2015 /   SciTech /   Leave a Comment

So, you want to do a PhD in biology? Well, there are several major decisions that you’ll have to make along the way. This guide attempts to explain each one in terms everyone can understand.

What University Should I Choose?

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The first decision you’ll have to make is where you want to do your PhD. This is like choosing the city where you’d like to grow up from a baby graduate student to a full-fledged PhD. You get to pick the type of people with whom you’ll grow up, the vibe, and what the world thinks of you when you say you did your PhD at Such-and-Such University. Most people think that this is a critical decision, but really, this is probably the least important PhD decision you will make, so don’t sweat too much over it. Flip a coin if you have to.

How Should I Pick My Advisor?

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A far more important decision is who you want to be your PhD advisor, or PI (Principal Investigator). When you choose your PI, not only are you choosing your mentor, but you are choosing your boss, your parent, your coach, and the person who, in large part, will determine your stress level and degree of happiness for the duration of your PhD. My best piece of advice here is to pick someone who is not too crazy. This may be impossible at certain Ivy League schools, or it may be that a particular PI is skilled at hiding the crazy until you sign your life away to his or her lab. Just do your best and try to pick a person that you are prepared to look stupid in front of for the next five to seven years.

How Do I Pick a Project?

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Once you’ve chosen a lab, you’ll have to determine your project. While perhaps not as important as your PI, your thesis project will have the power to make you feel like you are on top of the world one day and break your heart the next. Sometimes, you are lucky enough to know exactly what you want your project to be the moment you lay eyes on it, like love at first sight. Sometimes, your thesis project is an arranged marriage that your PI orchestrates. In either case, there are some things to watch out for. If this is your first go at research, just remember that, no matter how much you think this is the one for you, the first project virtually never works out. You may think you know what you like and want in a project, but the chances are good that you truly have no idea what you’re talking about. On the flip side, PIs are often natural-born salespeople who are trying to marry off their eldest, ugly, deranged daughter that all of their post-docs are wise enough to refuse.

Do You Have Any Specific Advice For Choosing a Project and/or a Date?

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My first two decisions placed me in a Harvard lab that studies proteins. Thus, my project choice involved choosing a protein I’d like to research in order to try to figure out what that protein looks like, what it likes to do, and what makes it tick. I can’t speak for other fields, but here are some basic rules of thumb for choosing a protein. Plus, this doubles as a dating guide, in case you need some help in that area and you’re not that into proteins.

Choose a protein that likes to come out and play

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I work with a membrane protein, which just means the protein lives in the membrane that holds all the cell guts inside. For those of you who don’t remember college biology (or, like me, never took it), the membrane of a cell is made of lipids (a.k.a. fats). Fats repel water, which is why you need a certain tough-on-grease dish soap when you’re trying to wash oil off a baby duck. The problem with membrane proteins is that, if your protein likes being cozy with molecules that don’t like water, the chances are good that your protein doesn’t like water either. This is a major obstacle because most techniques for determining what a protein looks like and what it does require that you pull the protein out of the membrane and put it in some water-based solution. Researching a membrane protein is sort of like dating the bubble boy, if the bubble was opaque, and also so small it can’t be seen with a light microscope. You want your date to come out and play, so you can get to know it, but that’s the last thing it wants to do, since it is basically allergic to everything outside the bubble. So, don’t choose an agoraphobe protein and don’t try to date tiny tiny bubble boys.

Choose a protein with a phone number

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Another important part of protein biochemistry is being able to get your protein away from all the other proteins in a cell. Scientists often do this by attaching a “tag” to their protein, which is usually just a little piece of another protein that’s easier to get ahold of than your protein. This is sort of like sticking velcro to all the red balls in the ball pit so that when you throw the balls at a giant dart board, only the red ones stick. Another way to look at it is getting someone’s phone number so you can separate that person from all the other people in the world. You want to do this because if you’re sitting in a crowd of people and someone is making an irritating noise, you want to get your date away from everyone else so you can make sure the noise isn’t coming from him or her. Some proteins, however, don’t like to be tagged and prefer to remain anonymous. You may find out their phone number or even give them a brand new phone, but they’ll just drop it, turn it off, hide it, or ignore it so that you can’t find them. This makes research and dating very difficult, so choose a protein (and/or a date) that responds to the phone.

Choose a nice average protein

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The other problem with my protein is that it’s really big. It’s about three times as large as the average protein in bacteria, so it’s kind of like dating a bear, which just isn’t practical. It doesn’t fit in the movie theater seats, taking it out to dinner presents a whole host of problems, and even sharing the sidewalk can be problematic. You could chop up your date into manageable pieces that will fit in a chair in order to get to know it better, but there’s really no guarantee that half a bear will act anything like the full bear. In fact, you can be reasonably certain that it won’t. I would just stay away from bears all together.

Make sure your “family” likes your protein

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Your PI may truly believe that you will be the one to work miracles with this protein, get it to emerge from its bubble, chop it into manageable pieces and get to know it, but PIs have evolved to be eternally optimistic. That’s how they got to be where they are—they always believe the next thing will work, and for them, something along the way did actually work. However, this may not be the case for you. If all of the protein’s exes (i.e. anyone who has previously worked with the protein) warn you to run away as fast as you can, this is a major red flag. The second red flag is if no one else wants your protein. Yes, it’s possible you just had great timing, and you managed to find the protein before anyone else saw how cool it is. However, more likely this means there’s something wrong with your protein like it is overly obstinate, abusive, extremely sensitive, or just an asshole. Listen to your lab mates who know the protein, and don’t try to be the hero. The protein will win.

I hope this handy guide helps you avoid some of the mistakes I’ve made throughout my PhD. Remember, the university you choose matters little, your PI matters a whole lot, and your project/date? No matter what, it will stomp on your dreams and crush you at times, but you can do yourself a favor and avoid the big heartbreakers by following simple rules listed above.

[“Average” illustration via Shutterstock]

Filed Under: SciTech Tagged With: biology, dating, protein

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