The Futile Cycle

Via evolgen, check out this music video, entitled “Scientists for Better PCR”:

I’ll dig more into these later, but here are two more papers that have particularly caught my eye this week, and which I intend to read in further depth:

In vitro reconstitution of the human RISC-loading complex (Open access!)

These authors have been able to form the RISC-loading complex, which is sufficient to cleave precursor microRNA and loads the miRNA onto Ago2. The entire complex is composed of Dicer, TRBP, and Ago2, without other Ago2-associated proteins that one would find in vivo.

Intranuclear Distribution and Local Dynamics of RNA Polymerase II during Transcription Activation

A lot of what we know about transcription and gene regulation in eukaryotes has been from reconstituted in vitro reactions, similar to ones described in the previous paper above. The problem is that the nucleus isn’t homogeneous; there’s all sorts of stuff in there, and people thought that that structure would be key to understanding gene regulation. One idea about gene expression was the “transcriptional factory,” which came initially from the observation that viscosity inside the nucleus is basically like water (meaning that stuff, like DNA, must be packed away to clear space), and that there seemed to be a particular spatial distribution of heterochromatin versus euchromatin in the nucleus. This paper strikes a blow against the whole “transcriptional factory” idea.

I just saw this in PLoS Computational Biology:
Matt: Local Flexibility Aids Protein Multiple Structure Alignment.

I thought to myself, Matt? What’s that?

Technically, it stands for “Multiple Alignment with Translations and Twists.” But really, “Matt” is just an algorithm named after the first author, Matthew Menke.

Cute or egotistical, what do you think?

There’s a really interesting paper out in PLoS Computational Biology that’s a follow-up to a paper I first pointed out a year ago, which appeared when PLoS ONE first debuted.

The new paper basically elaborates on the first paper’s computational basis, and they explore different things like “how does the amount of noise affect the selection of different cell states with different growth rates?” or “how general is this selection mechanism?”

Also, this paper invents a new word: “catalyzation”, which apparently is different from “catalysis.”

In any case, check it out! It’s a cool application of biophysics and systems biology to real, relevant biology!

I spent part of winter break at home helping my brother edit and submit his college apps, and it got me thinking about all the things I wish people had told me before I went to college. Here’s a list of what I think, as a recent college graduate, are the top non-obvious things that students should know before they go:

1. Get to know your professors

Yeah yeah, everyone says that, but really, this, along with the friends you make, is probably the most important thing you can do college, and it will have a lasting impact on your life. A good college professor can not only help you choose your classes, but he or she can also be a good mentor and advisor, expand your mind, and even help you find a job or help you get into medical/law/graduate school. These people will write your letters of recommendation.

In high school, it was easy to get to know teachers, even if you didn’t make much of an effort. Colleges are bigger, though, and professors are really busy. Most don’t seem to make much of an effort to get to know students beyond the classes they teach, but that’s not because they don’t like students; it’s because they’re busy teaching other classes, doing research, giving talks, or writing grants. Be proactive, seek them out! Go to their office hours (which are often surprisingly empty), ask them for possible research projects, ask them for interesting reading from their field. Professors are geeks; many of them love to talk about what they study.

Don’t stop talking to professors after the class is over. You need to build a better relationship than just the student-teacher one, especially if you plan on asking them for a letter of recommendation. The worst letters are the “this person got an A in my class” ones. They are pretty meaningless; most employers and schools will see your grades and/or transcripts anyway.

2. Go for scholarships and awards

Whether you sailed through high school with top honors and awards or barely made it through intact, you need to find a way to get good scholarships and awards in college. Employers and graduate schools love awards; when they hire and accept students with lots of awards, it makes them feel like they’re choosing a good candidate, because all these other people thought the student was good, too.

Besides, why would you say no to some extra cash or prestige?

But these things won’t just come to you. You need to go out and actively seek them, because most of the time, people don’t even know about them. Some of them are pretty obscure and unknown. Try looking at your college’s awards webpage (if they have one), or google for college scholarships and awards. It’ll be worth the effort, trust me.

3. Your grades don’t matter much…but they still matter some

You don’t need a 4.0 GPA; not even close. No one cares about the difference between 3.7 and 3.8. As long as you get a solid B+ average (3.5) or so, you should be fine, unless you’re absolutely sure you’re going to medical school or law school. Other stuff, like making friends, meeting professors, joining clubs, and going for scholarships and awards, is much better, and more fun besides. If your grades do turn out to be a little low, go work for a while before you go back to graduate school; by then, you’ll have had other experiences that are more important, and which will overshadow your grades on your applications.

Don’t fail your classes, though. It does look bad to have a 2.x GPA, and people will grill you about it, especially employers and graduate schools.

Still, try not to take all the easy ones, or all the hard ones. Challenge yourself in order to learn stuff and expand your mind, but don’t kill yourself over your classes. Find the balance. College isn’t a contest about grades. It’s about building relationships and a foundation for the rest of your life, and a few years out, no one will care what your GPA was in college.

That leads to…

4. Make friends

That’s a joke, right? Of course you make friends.

Well, this is more important than your grades. College is a school, yes, but if you want a job afterwards, your connections are more important, especially later on in your life. Join clubs. Make friends with smart people and outgoing people (outgoing smart people, of course, are even better). Maybe together, you can…

5. Start something

Something, anything. A club, a newsletter, a blog, a business, anything. Ok, maybe not another literary magazine; usually, colleges have 80 of those already, and don’t need one more. Starting something will show employers and graduate schools that you have initiative and creativity, that you don’t just follow the same old routine like everyone else.

It also feels good to start something and watch it succeed. Really work at it, and don’t just let it die. If it flops, hey, you got experience, and you can start something else!

Don’t worry that it’s not the most original idea, either. Google was yet another search engine when it came out, and Facebook was just another social networking site. Their success came from how they delivered it, how well they understood what the world wanted, and how hard they worked at it.

There’s something I’d like to point out to people, which is the absolute stupidity of mammalian gene and protein naming. Everyone wants their particular name, and names change over time in little petty feuds fought over the years, so now we have situations like this:

interferon- promotor stimulator protein-1 (IPS-1, also known as MAVS, VISA and Cardif)

Can’t we all be friends and agree to some sort of naming convention? Chemistry’s not perfect, but it certainly gets more orderly than we do…

Science (or rather, the AAAS) is renaming its online “virtual journal” from Signal Transduction Knowledge Environment to Science Signaling, and they present their annual solicited opinions from researchers on the best cell signaling papers from 2007.

Some cool highlights include (of course) the breakthrough somatic cell reprogramming papers from this year in humans (which are followups to the papers in mouse a year ago), but also the discovery of an acetylation cascade in interferon signaling, a feedforward amplification circuit in innate immunity signaling during viral infection by the creation of short RNAs, the elucidation of the mechanism of the cyanobacterial circadian Kai oscillator, and the discovery of the “cold” temperature receptor in mammals.

Check out the entire list at Science Signaling!

A great post from Marginal Revolution, where Tyler Cowen talks about how soldiers in the military seem to be eating quite well, on average. Of course, that’s not what he’s really talking about, but check out the post for a great analogy on why military systems aren’t necessarily generalizable to the public.

There are two classes of scientists that always amaze me in a “how the hell do they do that?” way.

The first are scientists that do fifty different things in ten different fields, excelling in all of them and contributing fundamental new discoveries in each of them. George Whitesides is a classic example of this. He’s been studying physical organic chemistry, microfluidics, surface chemistry, biochemistry, materials chemistry, nanotechnology, and even dabbling in a little origins-of-life speculation. The guy knows his stuff, that’s for sure.

The other side of the coin are those scientists that pick one topic and stick with it for their entire career, often for decades; the only thing that changes is their technique. Paul Schimmel is one guy like that; he has been studying tRNAs and tRNA synthetases for over 30 years, from before the advent of DNA sequencing through the modern genomic era. It’s incredible; I can’t imagine doing this. First, how do you find so many questions to ask about one topic? Second, don’t you ever get tired of this? And yet, even now, he’s still churning out Nature and Science papers on his obsession — there’s really no other way to put it.

There are a couple of neat papers from PNAS that came out recently, but this one was quite neat:

An alcohol binding site on the neural cell adhesion molecule L1

It’s kind of weird to think of ethanol as being a specific ligand to a protein. After all, it’s a solvent, right? Well, turns out that there are spots in brain proteins that bind ethanol (and similar alcohols), and one of them is in the neural protein L1. When ethanol binds there in fetuses, it can cause big problems for their neural development. There’s some neat biochemistry and pharmacology in this paper.