“Push electrons, not people.” I’m preparing for some really important interviews I have next week, where I have to talk about myself – past, present, and future-goals-y. So I’ve been thinking about this bumbling biochemist catchphrase a lot. It’s more than just a witty statement that popped into my head one day, it really is a motto that describes my outlook (and inlook) on life. Focus on helping other people, not tearing them down, and really try to appreciate the beauty of the biochemistry underlying our lives and help others see this beauty. 

Words cannot describe just how much I love biochemistry – and words cannot adequately describe what biochemistry even is – as scientists we can classify “types of science” based on the types of things we study and the methods we use – study living things? We’ll call you a biologist – wait, you’re studying those things at the cellular level? We’ll call you a cell biologist. Oh, *sub-cell* level? Like individual molecules? We’ll call you a molecular biologist. How they work at the mechanistic level? We’ll call you a biochemist. ⠀

And that’s just “biology!” But nature doesn’t have such classifications – everything is interconnected – the same chemical processes that powered dinosaurs power you – and you might even have some of the same exact atoms (basic units of elements like carbon and oxygen) they did. And those atoms can be joined up in different ways to give you sugar or fat or protein – or rocks. Science basically rocks!⠀

At the heart of much of biochemistry are proteins, which are like molecular workers. When you see the word “protein” in general use, you might think of some abstract thing that’s found in meat and nuts and quantified on a nutrition label. But that “20g” or whatever you see is hiding a lot of beautiful variation. Protein isn’t just some globby thing – it’s actually lots of copies of lots of different proteins, each of which is specialized to do some specific task (or a few related tasks). Proteins can do a lot of things, from holding structures intact, to bringing molecules together. 

Some of the most exciting proteins are “enzymes.” Enzymes are biological catalysts (reaction mediators/speed-uppers) that help out with reactions Enzymes are usually proteins (e.g. DNA polymerase), sometimes protein/RNA complexes (e.g. ribosomes), and sometimes RNA alone (ribozymes) and there are lots of different enzymes with different jobs & specificities. They bind to specific substrate(s) (things to be changed) and provide the optimal conditions in their “active site” for a reaction to occur. Enzymes can speed up reactions quadrillions of times but, the enzyme doesn’t really “do” anything – it can only help make something that was “possible,” “likely.” It’s kinda like the whole “you can lead a horse to water but you can’t make it drink” saying – an enzyme can bring reactants together but can’t make them react. Instead, enzymes lower the activation energy required to get the reaction going.

But, whether that reaction will actually go, that’s all down to the chemistry. Many reactions involve the transfer of subatomic particles called electrons, and this is where my catchphrase comes in. “Electron pushing” is a way that chemists show where electrons are flowing in molecular reactions. We draw arrows from the nucleophile (electron-giver) to the electrophile (electron-taker). One fishhook for 1 electron transferred and 2 for a pair. We care about these transfers because they’re how bonds are made and broken. And tracking the electrons is like the chemist’s version of “following the money.” But we can predict where they’ll go too :). And there are often places where they don’t really want to go… but enzymes can help convince them to.⠀

Case in point… I was watching a PBS documentary the other day on the chemist Percy Julian. It was talking about how there was this race to chemically synthesize (build from scratch) cortisol, a steroid medication that’s used to treat arthritis. All these groups of chemists were working on it, but they were stuck at this point where they needed to add a single oxygen molecule to a specific carbon molecule that didn’t really want it, and that carbon was pretty “generic” so there wouldn’t be a reason why the oxygen would get added there instead of a neighboring carbon. 

So, these teams were toiling away in the fume hoods and then this company, the Upjohn Company, stuck that precursor molecular in yeast and got the yeast’s enzymes to add that oxygen for them! Enzymes are able to do this because they provide great specificity, for example holding the molecule so that only the carbon site of interest is in the active site near the oxygen to be added – the horse’s nose is in the trough!

Clearly enzymes have a lot to teach us about chemistry, and how we can maybe make awkward synthetic chemistry reactions easier. But there’s still a lot that chemistry needs to teach us about enzymes. As amazing as they are, enzymes are not really “programmable” (at least not yet) because they’re too complex. They get to decide what they want to catalyze, where they want to try to convince reactions to occur. So in a way they’re less controllable than chemical reactions we do in a tube. 

Preparing for interviews, I’ve been thinking a lot about my long-term career-ish research goals and I think what sums it up is I want to use chemistry to investigate enzymes and enzymes to investigate chemical reactions. 

As we saw, enzymes can bring molecules together and give them the ideal conditions, but ultimately it’s those molecules themselves that do the hard work. And it’s chemistry that’s at play in every biochemical reaction. So you can understand a lot of biochemistry at a deep level if you try to “think like a molecule.” In organic chemistry class, my classmates were fretting trying to memorize all these different reactions and I focused instead on following the electrons and logicalizing my way through things. By focusing on mechanisms by which reactions occur, you can come to realize that if you understand one, you can reason out the others.  ⠀

I’ve kept this outlook throughout my scientific journey and, when people ask me for advice in “getting through” biochemistry or o-chem I tell them to focus on the mechanisms, the concepts, the “why’s” and then you can reason out the “what’s.” The other piece of advice I give is to try to enjoy the learning.  ⠀

It’s such a shame that learning all this is such a privilege but while you’re in the midst of learning it it’s hard to just stop and appreciate it. I’ve found myself enjoying biochemistry so much more now that I don’t have to worry about exams. I can just let myself soak it all in. And it feels so unfair that I get all of this knowledge others don’t have access to. In undergrad, when there was something I wanted to learn more about or check up on, I realized that a lot of science explanations are often either super dense or super watered-down, with little middle-ground. ⠀

So I started my blog, etc. as a way to help address the gap, with the “small” goal of explaining a huge array of biochemistry concepts, techniques, and classical experiments at a detail-full but jargon-less level. For the jargon part, you will see it in my posts, but you’ll also find explanations of what the terms mean. If you follow me (thanks by the way!) you know (and if you’re new to my posts you’ll quickly learn) I tend to take some liberty with word conventions, ditching jargon when possible so that understanding by anyone is possible (but still introducing the jargon so you can recognize it). ⠀

When I do this, it’s not because I’m trying to dumb down anything – in fact, it’s quite the opposite. Just because you don’t have the vocabulary to follow along with something doesn’t mean you don’t have the capability to understand it. Science is a lot like a foreign language and even the smartest people in the world need translators to translate foreign language for them – so if someone uses terms you aren’t familiar with, that’s their fault, not yours. So don’t feel bad if you can’t follow along! And apologies when I myself am guilty of this! ⠀

It’s not that we’re trying to be exclusionary or make ourselves sound superior (at least not most of us!). It’s just that, as scientists, we often use vocabulary that makes things easier for us, like formal chemical names that describe what’s in different molecules, making them easy to compare and predict how they’ll react – dihydrogen monoxide – must have 2 hydrogens and an oxygen! Since oxygen is much more electronegative, you have a polar molecule capable of extensive hydrogen bonding. ⠀

Did you get lost? Basically, “water’s sticky” because oxygen hogs the negatively-charged electrons it shares with the hydrogens, so it’s partly negative, the H’s are partly positive, and partial charges attract. As a result, raindrops are drop-shaped, water climbs up the walls of straws, and insects can walk on water! http://bit.ly/frizzandmolecularattractions

I think that it’s important to introduce this jargon to non-scientists but paired with a plain-language explanation. This allows people to navigate between the super-watered down “popular science” stories they might hear in the news and the super dense scientific articles those stories are about. Sometimes it can be really hard for me to bridge this gap, but I’m trying my best (and appreciate everyone’s patience as I bumble my way through all this while also a full-time grad student). This past year I added a glossary to my blog and in the blog forms of each day’s posts there are definitions when you scroll over underlined words. I hope this helps! http://bit.ly/bumblingbiochemistglossary⠀

In my grad school interviews, one of the questions I was asked a lot was whether my parents are scientists – nope (at least not officially – my mom did lead some pretty rad film canister baking soda/vinegar rocket launches!). And part of my inspiration for starting the bumbling biochemist was to help explain my work to them. Because I think it’s so cool – learning biochemistry allows you to see the same world at a whole ‘other level, see the beauty in the mundane, the surface tension in the rain. And I think it’s so unfair that I have all this knowledge thanks to being privileged to a great education. I don’t want to take it for granted. Instead, I want to give back and give forward. ⠀

Ultimately, I would *love* to be a professor at a small primarily-undergraduate college. When it comes to science education and training, I feel like undergrads are a really under-appreciated and under-serviced group. And it always warms my heart to get feedback from undergrads that they find my posts helpful! I would love to be able to teach undergrads in person in the classroom and hands-on in the lab – walking them through their first gels, their first protein purifications….⠀

Until then, I’m “practicing” teaching through my blog. Recently I’ve made some updates/improvements, adding pages where I’ve collected together experimental techniques, classical experiments, etc. So check it out! You can find it at thebumblingbiochemist.com under the “Let’s Talk Science” tab. 

It’s really important to me that I pass on what I learn – that to me is the biggest reward. I love science (obviously), but I really hate the competition aspect. Honestly, I don’t care about honors or prestige. In a grad school interview, when I said that I loved the fact that in science you can contribute “pieces” of a puzzle that can help advance the work of others – that even if you don’t make a ground-breaking discovery, you can still have an impact, building into a collective knowledge. One of the professors I met with basically saw this view as “aiming for the mediocre” – that I should focus on doing something that makes a huge leap. ⠀

Who defines ground-breaking anyways? Just because “conventional” ground isn’t being broken doesn’t mean that you aren’t breaking ground somewhere, for some person. ⠀

Kinda like opening a jar, you don’t see all the people that loosened it along the way. Things like the Nobel Prize highlight the work of the final opener. And it’s not that they don’t deserve recognition, it’s just that by focusing on them, we lose sight of all the hard work of those that enabled their work.⠀

Even things we take for granted, like being able to stain proteins blue with coomassie dye so we can see them after we separate them by size with a PAGE gel. Or knowing we could separate them that way in the first place. And maybe those proteins you’re running through that gel were recombinantly expressed (you took the gene from one place and stuck it into cells that’ll make it for you). Stop to think about just how amazing that all is. And it didn’t happen because of single people (although some of the people probably were single :P) ⠀

So what our society considers breakthroughs couldn’t even happen if people hadn’t have figured out that you can use a dye to bind proteins and then other people had optimized the hell out of it so you didn’t have to spend your time focusing on that. ⠀

So I’m fine if my major contribution in life is putting a piece of the puzzle together. Or even just helping someone else find a puzzle piece – or see see the pieces. Because you never know when that piece of a puzzle is part of a staircase.⠀

note: as for the more boring biographic part of who I am… I graduated from Saint Mary’s College of California (SMC) in 2016 with a B.S. in Biology. While at SMC, I became actively involved in biochemistry research, studying enzyme kinetics in the lab of Dr. Jeffrey Sigman. It was the summer after graduating, when I was mentoring a student in the lab, had some down time, and wanted to explain what I was doing to my family and friends, that the bumbling biochemist alter ego was born. I mean, that lab coat with cape potential was just calling out to me… 

In 2016, I enrolled in Cold Spring Harbor Laboratory (CSHL)’s Graduate School of Biological Sciences in Cold Spring Harbor, New York. I am currently a 5th-year graduate student studying biochemistry and structural biology at in the lab of Dr. Leemor Joshua-Tor. I research a process by which our bodies (and those of all sorts of critters) regulate what proteins get made when through a process called RNA interference (RNAi). Basically, if your cell wants to make a protein it first has to make RNA copies of the DNA recipes, and RNAi is a way to use short pieces of RNA to direct a silencing-complex to destroy specific recipe copies to prevent their corresponding proteins from being made. http://bit.ly/microRNARNAi.

note to my landlords – the wall art is removable decals, not paint or stickers! Thanks mom!

#365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0 ⠀

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