The dream: just one shot

We are engaged in an arms race with the flu virus, but we have a secret weapon hidden in our DNA.  We can make antibodies that neutralize a bunch of different flu variants.

Viruses are little packets of DNA cloaked in proteins.  We make antibodies that target the outer protein shell, flagging the virus as an invader to be destroyed.  In the arms race, viruses evade detection by making constant changes to that outer coating.  But not the whole coating, just a piece of it that is referred to as the “head.”  We might gain a foothold in this race because the flu keeps the same “stem” region across many of its flavors, including H1N1 and the much-talked about H5N1 (avian flu).  In response to the pandemic 2009 H1N1 infection, some people made broadly neutralizing antibodies directed against that stem region. We all have the gene to do it; the trick seems to be finding the right immunogen to show to the immune system.  The seasonal vaccines we get at the doctor’s office haven’t been able to elicit such a response, yet, though people who have been exposed to many flu vaccines are more likely to have broadly neutralizing antibodies.  So all those shots you got weren’t for nothing.

Research is bringing us closer to that dream of a universal flu vaccine.  It’s been making headlines in the big journals this month. A paper published in Nature this week shows what makes for a good universal antibody and how the immune system needs to display it.  A paper in Science Express earlier this month found that people can make broadly universal antibodies that target both influenzas A and B.  If all the pieces come together, it could be the end of annual flu vaccines for future generations.


Watching the world go by

Stingless bees live in dense tropical forests with canopies that reach over 40 meters (130 feet) high.  Lush as tropical forests seem to us, competition for resources is tough if you’re a bee.  When they find new food, they keep going back.  And they’ll bring friends.  How do bees remember where they found that last tasty morsel in a vast three-dimensional world?

Honey bees use a “visual odometer”, which gauges how far they’ve traveled based on the flow of images across their visual fields.  New research by a team from UCSD shows that the distantly related stingless bee does, too.  By papering stripes on the inside of tubes, which contained feeders of unscented sugar water, the researchers were able toy with the stingless bees’ visual odometer.  As the bees fly through the tubes, they see alternating black and white stripes.  Seeing the stripes pass by, the bees learned exactly how far into the tube they had to fly to find sugar water.  Once they were all trained up, the researchers altered the tubes and looked to see how the bees navigated. By varying stripe width (and therefore the number of stripes bees pass by on their way to food), they confirmed that stingless bees don’t count stripes.  Rather, they rely on their visual odometer, which tracks how fast the world passes by to estimate how far they’ve flown.  That visual odometer breaks down when the stripes run the length of the tube and their world looks…exactly the same.  Making the tube narrower or wider messes the bees up in a whole new way: the bees perceive the stripes moving at a different rate, and they navigate accordingly- going either too far, or not far enough.  Lastly, the researchers found that stingless bees use their visual odometer to measure distances in all three dimensions, not just laterally from the nest.  A good thing for bees that live in the forest’s understory.


My lemonade’s only half done.  Tell me more about these stingless bees!

Stingless bees don’t do the “waggle dance” like the honey bee.  They have their own form of communication: they jostle, vibrate, and make noises to share information with the colony.  Most of the information seems to be on the order of:  “I found food!  It’s super sweet!  And close!”  Not “go here for food.”  For the purposes of guiding hive-mates, they leave scent trails that can last about 10 minutes and they lead expeditions back to new food sources.  Stingless bees and honey bees are distantly related, though the stingless bee is much older, with the oldest known fossil dating back 80 million years.


A stingless bee can use visual odometry to estimate both height and distance.  Eckles MA, Roubik DW, Nieh JC.  The Journal of Experimental Biology, Sept 15, 2012. doi:10.1242/jeb.070540

Signals and cues in the recruitment behavior of stingless bees.  Barth FG, Hrncir M, Jarau S. Journal of Comparative Physiology, 2008.  DOI 10.1007/s00359-008-0321-7

Image credit:  David Cappaert, available under CCL.  Source:

The social networking game

Our lives are dominated by social interactions that seem to be getting ever thicker.  We make new friends in real world, follow people on Twitter, circle people on G+, and add “friends” to our Facebook pages, to name a few.  What governs how we behave in these and other social situations?  And why do we have so many “friends”?

Turns out, we’re nicer when we get to pick our friends.  As for why we’ve got so many, it’s probably because there’s relatively little risk to expanding our network online.  When the stakes are higher, people tend to limit their interactions to people who are nice to work with.

These findings come from social experiments using the classic strategy game, the Prisoner’s Dilemma.  The game is played over multiple rounds, and in each round players choose between cooperating and defecting.  There’s fallout from either decision, based on the player’s action and the actions of his associates.  The game can be mapped to social, business, political, evolutionary, and environmental situations.

In this particular version of the game, dubbed “The Social Networking Game” by the researchers, players accumulated points based on their network of associates.  Points were assigned as follows, tallied throughout the game and players paid out based on their score:

Cooperator-cooperator:  4 pts each

Cooperator-defector:  -1 point to the cooperator, 7 pts to the defector

Defector-defector:  1 pt each.

Defectors in a sea of collaborators stand to be victors, but if everyone behaves that way, no one gets rich.  Each game went on for 12 rounds.  Between rounds, people could forge new bonds or sever existing ones.  In general, people chose to expand their networks with other cooperators and tolerated the few defectors, but those few bad apples eventually spoiled the barrel.

So the researchers modified the reward system to really penalize the cooperators for keeping those defectors around:

Cooperator-cooperator:  4 pts each

Cooperator-defector:  -5 point to the cooperator, 7 pts to the defector

Defector-defector:  -1 pt each.

Now people formed tight cooperating networks for almost the entire game (when players know how many rounds are in the game, they switch to defecting at the end in a last-ditch points effort).  Furthermore, early defectors were swiftly booted from the circle and essentially ostracized.

So what does it all mean?

In casual social situations, when we get to choose our colleagues and prune our social networks, we tend to wind up in groups that are highly collaborative. Especially when there are serious consequences for acting selfishly.  Of course, we can’t always choose who we work with, and these findings apply to decision-making in a wide variety of interactions.  But in a day-to-day context, putting ourselves in situations that allow for updating our networks probably has some social benefit.  Online social networks are a paradigm of picking who your friends are and pruning your network.  It’s sort of this experiment on a grand scale.  Perhaps, then, part of social media’s attraction?

Image credit:

Reference:  Cooperation and assortivity with dynamic partner updating.  J Wang, S Suri, DJ Watts.  PNAS, epub Aug 17th, 2012- open access publication.

Let the musical (r)evolution begin

The noise was fit enough to reproduce, so its genes were passed on to its daughters.

Can we use the scientific method to understand how music evolves?  Evolution, with all the trappings of tenth grade biology: heritable traits, genetic recombination and mutation, and survival of the fittest?  To find out, scientists in London and Japan wrote DarwinTunes, a computer program that applied the tenets of evolution to 8-second loops of computer-generated noise.  Then they watched as popular choice turned noise into music.

The noises were assigned a “genetic code” that could be shuffled around and mutated, much like our DNA.  Thousands of people voted on how much they liked (or hated) the noises.  The best loops were allowed to “reproduce,” or pass on their traits to the next generation.  Then people voted again.  This cycle went on for more than 2500 generations.  Through this process of (quasi-)natural selection, the researchers found that music quickly came from noise, complete with western rhythm and chordality.   You can listen to the evolution for yourself, here.

But then it stopped evolving.

Computer simulations aren’t the only place that musical change has plateaued.  It’s happening in real life, too. Scientists in Spain analyzed almost half a million popular songs recorded from 1955-2010, looking for changes in pitch (harmony, chords, melody), timbre (instruments used), and loudness (not how loud you blast it in your headphones, rather intrinsic loudness).  They analyzed these three traits within songs and across time.

The results are in.  If you grumble every time you turn on the radio, prepare your soapbox.  Newer songs basically sound the same, with simpler chord progressions and less instrumental variety.  Not only is this uninspiring to listeners, it could prove problematic for song recognition programs.  As for what has changed:  everything keeps getting louder.

Maybe social media will save us.  Yes, popular songs have the same ring.  But we have an Internet full of digital music.  As people explore and share songs that fall outside of this homogenous norm, we will probably see musical evolution pick up again.  Which gets back to the role of the audience in shaping new music.  As the creators of DarwinTunes point out, the line between audience and artist is easily blurred in our digital day and age.  Digital music allows people to tweak and re-share the original piece.  Audience-induced mutations could introduce a selective advantage that evolution just might favor.  Or, put more simply, seek out music that’s different, and mix up the stuff that’s not.


Photo credit:  Mark Runyon/

Original Papers:

Evolution of Music by Public Choice.  MacCallum et al.  PNAS July 24, 2012 vol. 109 no. 30 12081-12086

Measuring the Evolution of Contemporary Popular Western Music.  Serra et al.  Scientific Reports 2, Article #521.  July 26, 2012.  DOI:10.1038/srep00521

Reconciling the new with the old

There is constant turnover in cells lining the gut.  In fact, this happens as often as once a day by dividing stem cells that live in the mouth, esophagus, and intestines.  The nature of stem cells in the esophagus has become a matter of debate, and it’s an important one to resolve if we’re going to understand diseases that affect cell turnover, like esophageal cancer, which has increased 3-8 fold in just the past 40 years.

Studies on cell turnover in the gut date back to the 1960s, when researchers injected radioactive thymidine into young mice.  Thymidine, often represented by the letter “T”, is one of the four DNA base pairs.  As cells divide, they incorporate radioactive thymidine into their DNA, which lets researchers track the cells over time.  Using this technique, all cells appear to divide and mature at the same rate in the esophagus.

The funny thing is that more recent discoveries don’t match up with the original reports from the 1960s.  Over the past five years, people have reported small reservoirs of slowly dividing stem cells in the esophagus.  The original “all cells are equal” conclusion is tough to draw from radioisotope labeling, so it’s not surprising that it’s been brought into question.

Science marches on, and now we have much better technology to track cell fate than radioisotopes:  we have transgenic mice.  A paper from the lab of Philip Jones at the Hutchinson-MRC Research Centre in Cambridge capitalized on this technology to sort out stem cells in the esophagus. Their work was published online by the journal Science on July 19, 2012.

The Jones group used two different mouse models to resolve the nature of esophageal stem cells.  The first mouse can turn on green fluorescent protein in the nucleus of all its cells.  Flip a biologic switch by injecting a chemical, and all the cells turn green.  That green signal gets diluted out as cells divide and are sloughed off.  In fact, it’s gone after just a month.  So it appears that there are no slowly dividing cells.  This agrees with the 1960s report.

Their second trick was to use a mouse that can turn on yellow fluorescent protein in cells of the gut.  It works like the first, inject two chemicals and cells turn yellow.  However, this mouse is different in two important ways: only some cells turn yellow, and their offspring stay yellow.  So researchers could track the fate of yellow cells in the esophagus.  Did they all mature and get sloughed off, or did some stick around as a reservoir of future esophagus-lining cells.

Turns out, there is a population of stem cells that sticks around in the esophagus. They divide to maintain their numbers while sending an equal number of daughter cells off to replenish the esophageal lining.  When nothing’s wrong, they divide about twice a week.  In the face of injury, the esophagus is like a boxer, light on its feet.  The stem cells ramp up their number of daughter cells to fix the damage, then settle down and go back to maintaining the status quo.

These nimble cells set the esophagus apart from the rest of the gut, which probably contributes to some of the recent controversy.  Elsewhere, you’ll find small pockets of slowly dividing stem cells. Esophageal cancer and gastric reflux both affect the rate of cell division in the esophagus.  It’s important to know who’s calling the shots on cell turnover when trying to treat these diseases, otherwise we might miss out on finding new treatments.

The original paper:

A Single Progenitor Population Switches Behavior to Maintain and Repair Esophageal Epithelium, Science DOI: 10.1126/science.1218835Published online July 19, 2012.

RNA fire alarm

“Inflammation” finds its roots in the Latin verb flammo, “to set on fire,” and it’s an apt descriptor of sunburn. As uncomfortable as it is, sunburn is actually a defense mechanism.  The inflammatory pathway that turns sunburned skin hot and red recruits immune cells to the damaged area.  The thinking goes that immune cells pick off skin cells with DNA damage before anything goes seriously awry (skin cancer).

How do skin cells sound the alarm that they’ve been damaged, as is the case in sunburn?  New research

by Jamie Bernard, a post-doc in Richard Gallo’s lab at University of California, San Diego, and their colleagues shows that damage to small noncoding RNAs can initiate the inflammatory response that’s better known as sunburn.  This is interesting on two fronts: one, we’ve long thought about DNA damage in the context of sunburn, but there’s much less research on UV-induced RNA damage.  Two, it’s another important function now ascribed to non-coding RNAs, once thought of as “junk” since they don’t get translated into proteins.

Bernard and his team found that UVB radiation damaged U1 RNA, a short strand of non-coding RNA in cultured skin cells.  RNA is single-stranded, but U1 RNA has an almost clover-like pattern, with complimentary regions looping around on themselves to create sections of double-stranded RNA.  As it turns out, UVB damage causes duplications of the loops, and these double-stranded fragments activate a protein (TLR3) that turns on inflammatory cytokines IL6 and TNF-alpha.  It also suppresses the immune system, which increases the risk of skin cancer, but can have therapeutic benefits in psoriasis or graft-vs-host transplantation.  In mouse models, the group was able to activate TLR3 simply by injecting UVB-damaged synthetic U1 RNA into the skin.

A few therapeutic treatments could fall out of this research. UVB phototherapy is currently used to treat psoriasis, a disorder in which immune cells stimulate skin cells to proliferate. Phototherapy is effective against psoriasis on several fronts, including toning down immune cell activity.   Maybe we can activate this UV-induced immunosuppression without the UV-aspect. This would reduce risk of skin cancer and eye damage.  Or, as the authors point out, by blocking the body’s ability to recognize bits of damaged RNA, these findings may help people that are especially sensitive to light, such as those with lupus.

In these sunny summer months, I find it a good reminder to use my sunscreen.

Balancing Act

Blood vessels in a mouse retina. Endothelial cells are blue, perivascular cells are red and green.

The key to blood vessel growth is balance: too much, or not enough, of any one signaling molecule can have disastrous consequences.  Embryos can fail to develop.  Vessels can burst, clog, and leak.  Vessels can also respond a little too vigorously to a tissue’s plea for more resources, growing in a messy disarray of dead-end tubes that blood can’t flow through.

While papers on blood vessels date back more than 150 years, we continue to have new insights into their biology.  We learned about the cells that make up the vessels: endothelial cells, which form the actual tube itself, and perivascular cells, which sit just next to the endothelial cells.  Capitalizing on this, we started growing “vessels” in dishes, which lets us study how blood vessels respond to signals in their environment.  We discovered small, secreted molecules in living things that encourage new blood vessel growth.  We developed ways to inhibit those signals.  And still, there is more to learn.

The field of blood vessel growth (angiogenesis) spans many disciplines.  Beyond understanding the basics as they relate to developmental biology, blood vessels reach into cancer, eye disease, stroke, heart disease, gastrointestinal disease, complications of pregnancy, and more.  The benefit of this is that discoveries in one field can inform the others.  Across these fields, there have been increasing reports of blood vessel regulation by microRNAs.

MicroRNAs are tiny strands of RNA that regulate protein expression by degrading messenger RNA (which contains the “message” from DNA) before the message gets translated to protein.  Thousands of microRNAs have been discovered, but not all have been ascribed a function, and many have functions beyond those initially reported. They are named with numbers, generally in the order of their discovery.

A paper published by Dauren Biyashev and colleagues in the journal Blood on March 15th 2012 describes a new role for microRNA 27b.  In the complex web of arrows that can be drawn to “explain” the dizzying number of factors that prompt blood vessel growth or stasis, microRNA 27b may sit near the top, regulating both vessel sprouting and artery/vein assignment, by acting on several distinct pathways.

Biyashev and colleagues found that microRNA 27b levels respond to pro- and anti-angiogenic signals in the environment, and that this one microRNA can prevent the translation of at least six different proteins that regulate blood vessel formation.  As such, it is a dial that can be tuned with broad-reaching downstream consequences.

As a master regulator, MicroRNA 27b helps keep many signals “just right” during blood vessel development.  Understanding the central role of this microRNA, and the growth factors that regulate it, may provide new rationale for existing anti-angiogenic drugs, or lead to the development of new drugs that target the microRNA itself.


miR-27b controls venous specification and tip cell fate, Blood, March 15 2012, Vol 119 (11).

Angiogenesis is controlled by miR-27b associated with tip cells, Blood, March 15 2012, Vol 119(11).