Christmas Letters

Hey everyone!  I haven't found a particularly compelling article to discuss in a while, so I'll be talking about Christmas Letters.  I tired writing my first Christmas letter for my wife and I, as this will be our first Christmas as a married couple.  It was a tough balance, I thought, between being entertaining and informative.  Anyway, I figured I'd ask my loyal readers what you want in a Christmas Letter.  Should it be honest?  Should it be funny?  Should it be informative?  Or would you rather just have a picture?  What would make the perfect Christmas letter?  Thanks for the input!

Kamikaze Protein???

Today I will review an article that I really enjoyed reading.  However, before we get to the article, I want to give you the backstory to how I came to read it.  It started on a regular lab day.  One of my friends posted a news article on Google Buzz that discussed this paper.  Of course, the news article heralded this paper as ushering in a cure for the common cold in a matter of a decade.  This was intriguing enough (and so difficult to believe) that I decided to read the article and formulate my own opinion.  After reading the article, I was thoroughly impressed by the science and the findings in the paper, and thoroughly disappointed in how over-hyped the news article was.  In my disappointment (and in my quest to generate even more followers), I tried to find a way to write about this article in a way that is 1.) Honest, 2.) Exciting, and 3.) Easy to follow.  The following is the final product of my labors.  I'll let you judge it.

The paper I'll be discussing, Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21), is currently free to read, so if you don't have access to PNAS through a university, you can still read it!  How awesome is that!  Anyway, in this paper, Mallery, McEwan, and Bidgood (three first authors) discuss a protein, TRIM21 and its role in immunity.  Now, before we can get into the details of the paper, we need a quick reminder of how our immune system works.  The immune system responds to pathogens (disease-causing organisms) in two ways.  First, there is a general recruitment of immune cells to the site of cellular damage.  This process is why your finger turns red when you poke it with a pin.  The second half of the immune system is what confers immunity and prevents you from catching the same disease twice (a la chicken pox).  This system uses proteins called antibodies.  Each antibody is designed to recognize a particular part of a pathogen and will bind to it, signaling for other immune cells to come and destroy the pathogen.

Viruses (which cause AIDS, the cold, the flu, hepatitis, and many other diseases) are pathogens that must enter a human cell and incorporate their genetic material into the cell.  In doing this, they hijack the cell and force it to make copies of the virus, which then go on to infect other cells and other people.  It was thought that, once a virus entered a cell, that the cell was pretty much a lost cause and should be killed by immune cells, sacrificing one cell for the good of the body.  However, this paper changes this line of thought completely.  For those of you not in science, this is a HUGE shift in thinking, and may very well be Nobel-prize-worthy.

Anyway, let's discuss this paper and its paradigm shifting discovery.  The researchers here showed that TRIM21 is a protein that, when expressed in cells at high enough levels, will prevent the spread of virus in cells in a dish, if the viruses are coated first with antibodies.  There are no immune cells present in this experiment, meaning that the eradication of the virus is being accomplished by plain, ordinary cells.  The researchers then go on to prove that TRIM21 binds to the constant part of the human antibody (meaning that it recognizes ALL host antibodies). 

What happens from here is a little less clear, though very exciting.  TRIM21 is an E3 ubiquitin ligase.  Ubiquitin ligases attach the protein ubiquitin to themselves or other proteins as a way to send the protein to the proteasome (where the protein is destroyed).  NOTE:  This is a very simplified and slightly inaccurate description, but it will suffice for the topic of this article.  It looks like TRIM21 ubiquitinates itself, targeting itself to the proteasome.  Because it is attached to the antibody which is attached to the virus, these both get dragged into the proteasome.  Thus TRIM21 is now the protein equivalent of a kamikaze pilot.  While the evidence for this is not strong enough to be confident that this is really how it works, the available evidence points in this direction.

All in all, this is an interesting paper with great science.  However, the assumption that this will quickly lead to a cure for the cold is somewhat misguided.  Antibody recognition of the virus is critical for the success of TRIM21-mediated viral destruction.  The cold virus is tricky, though, as it mutates frequently, making it difficult for antibodies to keep up with the virus.  Still, the  discovery is intriguing and changes our view of how immunity works.

All right.  Stay tuned for more posts!  Your homework is to post the popular-culture equivalent to TRIM21 (from film, literature, tv, video games, etc.)  I'm looking forward to your answers!

Musings, Updates

First the musings.  Thinking is to scientists as swimming is to sharks.  If a shark stops swimming it will sink, and if it doesn't have the ability to pump water over its gills or get water through spiracles, it will suffocate.  If a scientist stops thinking, they will sink.  Maybe not quickly, but eventually they will find themselves at the bottom.  This should not surprise anyone.  However, as scientists-in-training, graduate students must deliberately foster and feed this skill. 

It is possible, as a graduate student, to make it through your graduate career and get a Ph.D. without learning to think well.  You often spend much of your time troubleshooting one system, one protocol, one detail.  While this is important, one can forget the bigger picture.  To survive as a PI, one must have larger ideas, connecting themes from different subdisciplines.  So, the challenge to all you grad students out there, including myself, is to keep thinking critically.  Don't lose the forest for the trees.

That said, there have been a couple of articles released that I'm interested in discussing here.  One was recently published in PNAS that all my immunologist friends will enjoy.  The other two articles were published in Science and approach the same scientific problem with different techniques and tell different stories.  That post will be a compare/contrast that will take some time.

Lastly, I'd like to make some of my posts in video format.  Let me know what you're interested in seeing.  Should it be sports, science, or soul related?  Until the next post...

Ugh.

So the Chargers lost in brutal Charger fashion.  And the paper I picked out at the last minute was painful.  Painful.  So this will be short.

The article is entitled Contribution of Subdomain Structure to the Thermal Stability of the Cholera Toxin A1 Subunit.  It was published in Biochemistry earlier this month.  Let me be frank.  This is a bad paper.  Unless you really like looking at CD and fluorescence data at different temperatures to monitor unfolding and only that, don't bother.  The only figure that doesn't fall in this category is a structure of the protein that was produced by another lab.  Ugh.

The writing was decent considering the data the authors had to work with.  The one conclusion they could make with their data they did, even though the data don't strongly support it.  There was support, just weak.  Good writing can only do so much for an article.

So am I angry at the authors?  No.  This is probably a thesis project that never panned out technically and the grad student needed a publication.  And the writing was good.  The science just stank.  So kudos to the grad student for being able to get that data published.  And good luck in your future endeavors.

So, to conclude, the science in this paper stinks.  Don't read it for that.  Don't read it unless you're really interested in folding/unfolding.  Good night!

The New U

Welcome one and all to the first sports-themed post on the blog.  I don't know how many of you out there are actually reading, but I imagine that most of you have an inkling of my sports affiliations.  For those of you that don't, here's a quick and easy list of teams I love and teams I hate:

NBA:
Love: Nobody.  The Hornets left Charlotte, Stockton and Malone are retired, and I refuse to pull for an organization that is being ineptly run by Michael Jordan.

Hate: Nobody.  Hard to pick one team I really don't like here.

NHL:
Love: Carolina Hurricanes.  I don't follow them religiously, but I'll pull for them over anybody, and will know at least a little about them.

Hate:  Not really any team I hate.

NFL:
Love: San Diego Chargers.  I love them.  Period.  Was beginning to understand football when they last went to the Super Bowl (1995, painful).  Also, Philip Rivers went to NC State. 
Carolina Panthers.  Was in NC before they started.  Hoping they can pull a team together and get an identity going (besides being a pushover).

Hate:  Oakland Raiders, Denver Broncos, KC Chiefs.  AFC West teams, all with annoyingly cocky fans.  NE Pats.  Because they're the most recent bandwagon team.

MLB:
Love: San Diego Padres.  Tony Gwynn is my favorite Padre.  They had a good team this year.  Hopefully they'll be even better next year.

Hate:  Yankees and BoSox.  Bandwagon teams.  I tend not to hate the other NL teams as much for the following reasons: SF-wins in a similar way to SD.  LA-Had a good roommate who loved the Dodgers.  CO-Fun to watch.  AZ-Does anyone take them seriously now?

College:
Love:  NC State.  Period.  Hands down.  Went there.  Was in the athletic bands.  Case closed.

Hate:  UNC-CH, Duke, WF.  Should be self-explanatory.

So now I've listed my teams.  And the ones that will never be my teams.  And yes, my wife knows that I struggle to be happy for her when UNC does well.  That's another story for another blog.  But now that you know my affiliations, you can take what I say with a grain of salt.  Or five.  Especially this time around.

Last weekend was bad.  State lost.  The Chargers lost.  It was bad.  Period.  This week things should be better.  State doesn't play and I'm lowering my expectations for the Bolts.  What does that leave me to talk about?

THE BUTCH BOWL!

We call the UNC-CH - Miami game the Butch bowl, as he was the former coach at Miami.  UNC has won the past three games with Miami, and looks to make a good shot at this one.  However, I don't feel comfortable enough with either team to make a good prediction.  UNC has two good wins against quality competition (ECU and Clemson) and 1 bad/mediocre loss (GT).  Miami lost to two good teams, FSU and tOSU.  They've beaten everyone else.  And they need this win to stay in the Coastal race.

While this game is important for both teams, each looking to win the Coastal, I think there's something even more important going on here.  Last year after beating Miami, Marvin Austin (a UNC player) said “We’re The U! F--k them! We’re The U!”  Thanks DTH!  With the shenanigans going on in the UNC football program and they're recent exposure (via Marvin Austin's twitter and NCAA followup), we'll be witness to something special on Saturday.  The transferring (at least in part) of a title.

Miami is no longer the U.  Gone are realistic chances for a National Championship.  Gone are the sanctions.  Gone are the agents.  Gone are the thugs (hello Florida Gators).  In all recent respects, UNC is now the U.  Sanctions are coming.  Agents are here.  So are thugs.  And so are the wins.  Well...okay.  If you count 8-5 with a bowl loss as U-worthy wins, then yes.  And at UNC-CH, a basketball/women's soccer school, that may be all the U mojo can get them.  So, while this Saturday's game may be the Butch Bowl, it's also the New U vs. the Old U. 

Stay posted for Sunday's science post.  And, as always, comments are welcome!

New F-actin Model

So I’m trying to be punctual with this next science update.  Today’s article comes from the journal, Nature.  It discusses the structure of F-actin, or filamentous actin.  Actin is a protein that polymerizes to form a long chain.  In its non-polymerized state, it is known as G-actin, and in its polymerized state, is known as F-actin.  Actin is very important for cell motility, muscle behavior, and a host of other functions.  Many, many scientists now study actin, its dynamics, and proteins that interact with actin.  For a simple review of actin, I recommend Wikipedia.  

Anyway, let's get down to the heart of this paper: Direct visualization of secondary structures of F-actin by electron cryomicroscopy by Takashi Fujii and colleagues.  Because this article was published in Nature, it is short.  This provides a unique challenge for authors, as oftentimes scientists have much more to say about their work than they can squeeze into the limited confines of a Nature article.  It is interesting to see what the authors view as the most important aspects of their work and what is relegated to the Supplemental Information.  

The authors submit in this paper a methodology for using cryoelectron microscopy to get a high resolution structure of F-actin.  They end up with a 6.6 Angstrom resolution, not nearly good enough to show side-chain conformations, but good enough to see the secondary structure and to arrange the individual actin subunits.  In doing so, the researchers show that the individual F-actin subunits do undergo significant changes in structure compared to their structure as G-actin.  And these comprise the two biggest findings of the group.  The technical advancement and the structural advancement. 

It's going to be difficult for me to discuss/critique the science to great lengths here, as the innovation and process the researchers took to get their results relied on advancing cryoelectron microscopy.  That said, it seems like this technique could be applied to other thin biopolymers (On a side note: are there any others?  Feel free to chime in and help me out, science friends!).  The results here are more interesting to me anyway (than the technical aspect of how they got the results, though that's important).  I thought they authors did a good job in this regard, leaving much of the technical aspect in the Supplementary Info and spending more of their time writing about the structure and its implications in actin behavior.  The researchers also did a decent job at keeping the paper from sounding like your average structure-for-the-sake-of-structure paper.  Their emphasis on the consequences of structural changes was welcome, and only for a couple of paragraphs did they revert to some of the basic interactions.  All in all, the science was explained well and the importance/novelty of the work was appropriately emphasized.

Quick note on the figures.  They were very good.  Colorful and attractive, though also informative.  The authors highlighted the most important structures and changes, and designed the figures appropriately.

The authors suggested the next logical step being to do cryoEM on F-actin with other proteins bound (those that interact with F-actin).  While this is obviously something we as scientists would like to know (gives us new molecular interactions to target with drugs), I'm not sure how effectively one can coat these fibers.  As the technique relies upon the repetitiveness of the polymer for its accuracy, getting efficient and regular binding along the fiber may be difficult, limiting the resolution of such a structure.

If I was to follow up on this article, I would run some simulations to determine how the thermodynamic stability of the actin monomer changes as it is incorporated into the filament, using this new structural model for F-actin.  As the authors alluded to, it seems like the actin subunits of F-actin may be "spring-loaded" as they are incorporated.  In other words, they adopt a less stable conformation that is supported by external contacts (interaction with other units of the polymer).  Again, as the authors mentioned, this internal instability may help to explain actin dynamics in the cell.

Well, it's been a long weekend, so I'll wrap this up.  This paper comes across as well written and informative.  I'm not sure if the findings are quite Nature worthy, but are definitely worth giving a cursory glance.  See you all next time!

The First Science Post

Here we go.

The first science post will concern an article that, had I not been looking for a particular technique, would have never read, much less found.  This article comes from the Russian Journal of Bioorganic Chemistry, Volume 28, Number 2, year 2002, from pages 136-146.  It was written by V. N. Danilevich and E. V. Grishin and is titled A New Approach to the Isolation of Genomic DNA from Yeast and Fungi: Preparation of DNA-containing Cell Envelopes and Their Use in PCR .

First, a quick summary.  If you didn't get it from the title, this article describes a new, simplified method for isolating DNA from yeast and fungal species for analysis by PCR (for the non-science readers, a way to get the DNA, in a usable form, from certain species that are not always the easiest to get DNA from).  The authors apply this method to a number of different strains and use control PCR reactions to prove the worth of their method.  This method is relatively simple, as it requires some heating, cooling, and centrifugation.  That's about it.  No glass beads, no mortar and pestle, no sonication.  This makes the procedure simple and easy.  The authors then go on to show how this method can be used to do some basic fingerprinting to aid in classification of yeast/fungal species.  I'm not going to focus on that as I am not a geneticist.

So now that you have a basic idea of what the article is about, let's get into the science.  First, there's a reason this paper isn't in Nature, Science, JBC, etc.  It doesn't have the impact that some of these others do.  It's biggest contribution is in providing a better way to extract DNA from difficult fungal species for use in evaluating the genome of these yeast.  However, the "weaker" journal is not indicative of the way the science was done.  The authors do a good job explaining why they ran certain experiments to test changes in their methods.  There are appropriate controls and measurements at each step to show what went where.  Their final conclusion about the DNA and RNA left behind, in an insoluble lump, seems fairly reasonable and has a citation for further clout.  I don't have any particular problem with the science, other than it being somewhat boring.  Necessary, but boring.

The way in which the article is written is a solid mix of good, mediocre, and bad.  How much of this (if any) is a result of translation and cultural differences is difficult to discern, but we'll continue on with the critique as before.  The style of the article is probably its strongest point.  For being an article on a less-exciting problem, the style is very engaging.  The paper reads like a story (or as much of a story as I've seen in a journal article), which is especially nice, considering method papers tend to be droll.  The figures used are fine: all gels showing PCR product or isolated nucleic acids.  Nothing to write home about, either good or bad.  The weakest part of the article, from a writing perspective, is its organization.  A method paper should be straightforward in its organization, as readers will likely try to emulate the results or apply them to a slightly different system.  This article lacks such organization.  All the necessary details are present, but they are not presented in a way that makes the reader's job easy.  An easy way to fix this would be to include a flow chart of the process.  One more figure that would fix 95% of the organization issue.

All in all, this is a fair paper that sufficiently, but not masterfully, does its job.  The science is useful, but not particularly groundbreaking.  The next article I'll review is from a recent Nature publication concerning the secondary structure of filamentous actin.  Now I'm off to purify some DNA from yeast...

Sorry...

To those of you following my blog, I'm going to let you down already.  The science post will have to come out tomorrow, as today's been busy.  Getting married makes you much busier.  So please accept my apology. 

Also, the Chargers bungled away their winning streak against the Raiders and lost a chance to gain ground on the Chiefs.  Still getting over that one.

Purpose

Welcome to Science, Sports, and Soul, the blog of a graduate student at UNC-Chapel Hill.  I'm not going to spend too much time or space on this entry, but will instead lay down the purpose(s) of this blog.  Without further ado:

Purpose1
This blog will serve as a way to improve my writing ability.  I do not consider myself to be a horrible writer, nor do I consider myself to be a fantastic one.  You may come to a different conclusion upon reading a few entries, but I would consider myself to be a "fair" writer.  Not good or poor.  Just fair. In writing this blog I hope to become more familiar with writing, particularly scientific writing.  As a budding scientist, learning how to effectively communicate through writing is paramount to my success.  I've struggled through too many dull and poorly written papers and do not wish the same fate upon students who read my work.

To aid in fulfilling this purpose, every Sunday I will update this blog with a post concerning a scientific paper that was recently published.  I will provide a brief synopsis and then a critique of the paper and the science.  These entries will be much more technical and may be of little interest to a number of readers.  For this I apologize.

Purpose 2
This blog will offer me an avenue for reflection (the Sports and Soul part).  It is imperative for that I take some time and reflect on things.  As I age and take on more responsibility, I find that this need grows ever greater.  Some of my reflections will be philosophical, others purely fun.  All will give me a chance to breath and refocus.

So, with that out of the way, welcome to my new blog.  Comments are most appreciated.