Tuesday, August 31, 2010

Getting ready for fall quarter

This weekend I finally got a piece of paper (not just spoken assurance) confirming that I will be teaching microbiology at Davis this fall. This means I’d better get cracking on the class. I should update my lectures, start gestating exams, and of course start working on this year’s haka.


A haka is a highly ritualized dance and chant in the New Zealand Maori tradition. Probably the most famous haka is the one performed by the New Zealand rugby team, the All Blacks, before each match:

The All Blacks Haka is intimidating, and it serves a purpose general to all hakas. It establishes a relationship, honors both members of the relationship, and clearly states the nature of the relationship. This haka, “Kapa o Pango,” concludes “Our dominance / our supremacy will triumph / and be placed on high! / Silver Fern! All Blacks! / Silver Fern! All Blacks!” The hand gestures emphasize the words, and the bulging eyes and extended tongues are to intimidate the opponent. Other hakas are gentler, with words and gestures that honor heroes or welcome guests.


Like the applause at the end of the quarter, the introductory haka is an academic tradition apparently unique to Davis. The origin of this tradition has to do with the unique circumstances of the university’s founding, and the surprising connection between central California and the South Pacific. It’s relatively well known that John Sutter, the Swiss √©migr√© who founded Sacramento, came to California after a sojourn in Hawaii, and brought many Hawaiians with him. Less widely known is the connection between Davis and New Zealand. In 1906, when the University of California “University Farm” was established in rural Yolo County, there was a scramble to find experienced faculty for a diversity of agricultural programs. In addition to a viticulturist from Alsace and a rice specialist from Punjab, one of the hires was an expert in sheep husbandry, R. W. MacLaren, from New Zealand. To start without the need to train helpers, MacLaren brought with him a dozen of his own from New Zealand, including eight Maori men and their families.


Tragically, MacLaren died after only three years in Davis; homesickness drove him to drink, and he succumbed to liver disease. Before his demise, as a result of his growing debility, his teaching duties had been assumed by his chief assistant, the Maori shepherd George Te Wainoare. Te Wainoare went on to teach at Davis for over a decade, establishing excellent practices in the California sheep industry.


Te Wainoare also established the tradition of greeting his new students every year with a haka. A 1910 letter from sophomore L. H. Teter describes how “before so much as saying hello, the professor danced and yelled at us like a demon, sticking his tongue out at us. Clyde [Deacon] started laughing, but Nibs [Robert Gibbons] seemed genuinely scared…Teywiner [sic] explained that this was his people’s way…” Te Wainoare’s was a beloved teacher who enjoyed warmly collegial relationships with the rest of the faculty. This, combined with the strong strong Maori influence at “the farm” (there were eight Maori families, and only nine students in the first graduating class), it is not surprising that other professors and their helpers started doing their own hakas. The haka was well established at Davis by the time Te Wainoare returned to New Zealand in 1926.


The haka has evolved over a century in California. Professors still write their own hakas, as I must do now for my introductory microbiology class, and the content of the haka is appropriate to the class. The haka is still generally performed in the Maori tongue, though they have been done in the native languages of foreign-born professors and even, it is rumored, in Latin. As a bow to modern times, I will use the campus translation service to arrive at a serviceable Maori rendition (as well as to find suitable Maori words for “bacteria” and “microscopic”).


Despite these changes, the haka still serves to establish the relationship between professor and student. Students expect (and appreciate) a good, creative haka vigorously executed by the professor and the TAs. In return, each incoming freshman class composes a haka. This haka is performed only once, by the entire class, in an extremely moving ceremony during their graduation exercises.


I still haven’t worked out this year’s Microbiology 102 haka, and the haka is (by tradition) never recorded nor is the Maori chant written down. However, here is the English for last year’s introductory biology haka. I have to say that when the TAs and I performed it, it made quite an impression.

O ye small fry!

You were big fish in your pond

But we are sharks, we are sharks!

With this red pen

Your answers will bleed, will bleed!

We are the sharks!

We drive you and push you,

You will be lost, you will be confused!

The test will come

You will shake, you will tremble!

Would you contend with us?

Be rigorous

Hit the books, hit the books!

Consider and think

Grow in wisdom, in wisdom!

Be rigorous!

Consider and think

Then see us eye to eye!

Monday, August 30, 2010

academic blues

I was out walking Opal the page-turning dog the other day when I ran into M, who was walking her dog Petunia. While Opal and Petunia socialized in their doggy way, I talked with M, a biology professor who recently retired from Sac State. She no longer teaches, but she does a lot of advising. I rely on her for updates on Sac State, and she gets the skinny on developments in biology teaching at Davis from me.

The situation at Sac State does not foster optimism, for me or for the state's undergrads. The state's budget woes are terrible and unfortunately routine, meaning that the academic year starts without a budget. Classes are being cut, and M tells me that the biology department is experimenting with much larger classes. Despite this, classes are being cut. As an advisor, the best advice she can give many students is cynical and depressing: hope that many of your classmates fail.

This is unfortunately a reasonable hope. The bottleneck is introductory classes that must be completed for a major. Too many students can't hack these classes because they don't have the study or thinking skills required. They graduate from high school having been taught to take a specific test, rather than having been taught how to learn or think. And, as any geneticist knows, you get what you select for.

So, both at Davis and at Sac State, students are now taking classes--time consuming, full tuition, not-for-credit classes--to prepare for starting a major. Part of me is happy to see these, because I know from my own experience that they're necessary. But, I'm vexed that these classes are even necessary. And, as M informed me, they have a terrible attrition rate.

Addiction comes from infrequent, random hits of good feeling, and the individual successes in education are what make teaching so addictive. However, the vast majority of academic news these days is just so depressing.

Friday, August 27, 2010

Bowhunting

A big chunk of our time in the last week has been consumed with the quest for the ideal violin bow. Like the ideal violin, the ideal bow is a chimera. The ideal bow is light, so it can be moved prestissimo possible; however, it is also extremely strong, so that it can transmit the player’s energy to the violin string. The ideal bow is supple, allowing the violin to sing like the human voice, and it is also rigid, so that it can ricochet and jump off the strings. The ideal bow is completely self-effacing, a passive conduit that relays the violinst’s thought from hand to string, and it also has a unique, charming personality that brings new character to the violin. Since every violin is different, the bow that works for my violin won’t be the ideal bow for Duva’s violin. And since we are who we are, the ideal bow has a price tag less than $3,000.


There are two motives behind our quest for a new bow. One motive is a new violin, a fiddle that Duva purchased “in the white”, rethicknessed, varnished, and set up. The other motive is that, during the summer violin-building workshop, we both got to play something very close to the ideal bow. It was a Tourte. Tourte (who lived around the turn of the 18th century) was the Stradivari of bowmaking. This bow was everything: light and strong, supple and rigid, neutral and charming. It made every violin sound so much better and gave even the worst of players (specifically, me) confidence in their ability to produce beautiful singing sound. When I closed my eyes, I felt as if the bow vanished, and there was a direct communication between my hand and the violin.


There is only one way in which a Tourte falls short of the ideal. They are available at auction only rarely, and could set you back $100,000.


So, the quest. It involves the hour-and-a-half schlep out to El Cerrito, home of Ifshin’s violins, a wonderland for string players. Once there, and once a price range has been established, we are presented with a bunch of bows and escorted to an acoustically-sealed practice room. Then, to the best of our meager abilities, we push the bows, one by one, in extremis. Find the balance point. See if it bounces off the string and lands on the string evenly over the length of the bow. Check for nimbleness off the strings with Kreutzer’s Etude number X. Try for long singing tones with the “Meditation” from Massenet’s Thais. Listen to yourself play, and if possible, stand across the room while the other plays. Then comes the impossible part—remember how the bow performs, and mentally compare it with the next bow, and the next bow, and the next bow…and after ten bows, try to narrow your choices down to three. The fine folks at Ifshin’s allow you to take these three bows home for further trials.


The next stage is to run the bows by our violin teacher. She has vastly more experience than we do, so we value her judgment on these matters. So, she does the same test that we do. With one, she makes a face like she bit down on a moldy strawberry. With another, she plays a bit, then plays some more, clearly liking the sound, plays some more, and shakes her head when trying the Kreutzer, and plays some more. She produces her report: this one is lively, that one is lyrical, this other one is…well, she knows the perfect word in Estonian, her native tongue. But talking about bows is like talking about wine, prone to poetry and utterly unreachable by accurately descriptive communication.


With her evaluations, it’s on to round two. The process repeats—a drive to Ifshin’s, an attempt to translate our teacher’s feelings into precise adjectives to tell the sales clerk, an hour of etudes until everything sounds the same to fatigued ears, sifting and winnowing, and a new trio of bows to choose from.


We’re at a stage where the bows we’ve selected meet with our teacher’s approval, though not her enthusiasm. No one bow stands out. Of the three bows, I like the mid-century German one for its Steinway-like neutrality. Our teacher likes the modern American one for its responsiveness and power. Duva likes the mid-century French bow for its lyricism. I have a feeling we’ll be going through at least another round of this process, and of course, we will never find the ideal—unless we somehow get a Tourte.


Violinists talk about the intimate relationship they have with their instruments in terms reminiscent of the terms most people talk about their life partners. However, most of the violinists I’ve met—that means, musicians who don’t have a Tourte at their disposal—play a bow that they are merely reconciled to playing. They have actively wandering eyes, and few of them would hesitate to abandon their current bow for something better.

Thursday, August 26, 2010

Friday Flora: More from Spicer Meadows Reservoir

A couple more flowers from the trip to Spicer Meadows Reservoir. Both of these were growing in a cascade that emptied into the reservoir--a beautiful spot, shady and cool, and also the home of an ouzel. I didn't get a picture of the ouzel, but a photo wouldn't do much. To get the full ouzel effect, you have to have a movie. They are the bounciest creatures this side of Kangaroos, and seem endlessly cheerful.

Anyway, a wild onion:

And a lily, with a bit of the forest submerged in the reservoir in the background:

Wednesday, August 25, 2010

The swindle

I sometimes feel as though I need to apologise to my students. It's not that I am suffering from impostor syndrome. After five years of teaching, I'm mostly past that. The problem is that I sometimes feel that I am part of a con being run by the UC, an educational swindle. The UC offers something for sale, specifically, an education. Then, in exchange for the students' (parents') money, what is actually given is a summer session class: compressed, accelerated, pared-down, and severely compromised, with a slightly lower-than-average class of students. To be sure, there are some students who are not swindled. The go-getters are perfectly capable of thriving in these classes, and get their money's worth. There is also a class of students who are not after an education, but instead are pursuing a diploma. These students are also not swindled--as long as they get their passing grade, they have also gotten what they paid for.

However at least half of the students are simply not prepared to take the class. Their high school education or their freshman and sophomore classes leave them with inadequate study and thinking skills to cope with the class. As a result, they do not get the education they paid for. They might, if the summer classes were not compressed, or if K-12 education in California had not been gutted. But this is not the case, and the UC knows it, but continues to run the scam.

The UC's scam could be viewed as part of an intergenerational swindle. Michael O'Hare, a UC Berkeley professor, has posted a letter to his students apologizing for his part in this scam. You should go read the whole thing, but it starts:

Welcome to Berkeley, probably still the best public university in the world. Meet your classmates, the best group of partners you can find anywhere. The percentages for grades on exams, papers, etc. in my courses always add up to 110% because that’s what I’ve learned to expect from you, over twenty years in the best job in the world.

That’s the good news. The bad news is that you have been the victims of a terrible swindle, denied an inheritance you deserve by contract and by your merits. And you aren’t the only ones; victims of this ripoff include the students who were on your left and on your right in high school but didn’t get into Cal, a whole generation stiffed by mine. This letter is an apology, and more usefully, perhaps a signal to start demanding what’s been taken from you so you can pass it on with interest.

I can't apologise for Proposition 13, having been too young to vote when it passed, and I have generally voted with the losers in most California elections. Nonetheless, along with Dr. O'Hare, I proffer my apologies to my students.

Tuesday, August 24, 2010

Tuesday Musical Creep-out

My piano teacher brought this phenomenon to my attention. Seems appropriate after yesterday's Monday Musical Offering.

A bit creepy--a little like Beethoven via North Korean Mass Games.

Monday, August 23, 2010

Monday Musical Offering

(Inspired by Ron Butlin’s “Vivaldi and the Number 3”)


The notation grew thicker and tangled like a bramble, and somehow the notes themselves managed to look angry as they clung to the staves. The pen moved faster and got drier, finally just scratching the manuscript paper.


The composer paused as he dipped the quill in the inkwell, looked at what he had just written, and scowled. He ferociously scratched out most of what he’d just written, and spilled ink over the remainder. He threw away the quill, crumpled up the manuscript paper, and slam-dunked it into the recycling bin by his desk. He rose, strode over to the kitchen, counted out sixteen coffee beans, ground them, and ransacked the cupboards for a filter. Finding none, he went back to his desk, retrieved the crumpled manuscript from the recycling bin, and folded it into a rough cone. In went the grounds, in went the water, out came the inky coffee into the “World’s Greatest Composer” mug his no-good nephew had given him.

He angrily fished his cell phone out of his pocket and angrily punched the number (it seemed he did everything angrily, his analyst had told him. Of course, this was after he had angrily punched his analyst).


“Louie! Dammit! I’m thirsty!”


The voice of someone who did not want to be distracted answered. “Ludwig …What?”


“Louie, I want beer. Beer costs money. You’re my agent. You’re supposed to get me commissions, patronage! Pay for beer! You haven’t! Why am I giving you a percentage?! Where’s my beer? I can’t compose on coffee!”


“Ludwig, baby, calm down.” The agent took a few moments to figure out just what was going on with his cranky client. “Hey, I lined you up with that sweet gig with Archduke Rudy. Ain’t that going OK? He’s still rolling in the florins, ain’t he?”


He’s rolling in florins. I am not. I need more gigs, Louie.”


The agent sighed loudly, as if he had to explain the concept of sharing to a three-year-old. “Look, Ludwig, the public’s kinda cool on you right now. Need I remind you how the reviewers felt about those dissonances in the Eroica? And the snit the censor had about Fidelio? And I’m doing pretty good to get any of your sonatas published. Nobody can play ‘em! Look, Ludwig, could you write something catchy, something hummable…something that will sell? Do that, and you can buy some beer—hell, I’ll buy you some beer!”


“Dammit, Louie, it’s 1806, I’m at the peak of my middle period! It says here in Grove’s that I’m a mature composer, writing heroic music, stretching the boundaries of the classical style! I can’t go writing dancehall music. It’s not heroic!”


“Ludwig, you want money for beer, you write music that people will pay for. It just so happens that I was about to call you. I’ve got a juicy commission for you.” Unheard by Beethoven, the agent was desperately flicking through his PDA. “Novelty act from Tyrol—“Josef Dreck und seine tanzenden Kuhen.” Joe got himself some Scottish Highland cattle for his act, and he needs some Scottish music for them to dance to. Something light and catchy. Nice tune, steady beat, cow could dance to it.”


“What!?! Me? Ludwig van Beethoven,” he roared into the phone and looked at his mug, “the world’s greatest composer? Music for dancing cows? Impossible!”


“Come on Ludwig, sweetheart, be reasonable. You could bang it out in fifteen minutes. Just do the piano score. Schuppanzigh can orchestrate it for you. Dreck’s willing to give you fifty florins up front plus 10 percent of the door and your name on the marquee…”


“Bah! I would pay to have my name removed from the marquee!”


“…just some nice easy Scottish-sounding tunes,” continued the agent, ignoring Beethoven. “You know, the censor himself was seen at Dreck’s latest show, he was quoted in Variety as saying “it was better than ‘Cats.’” This might just get you back into his good books, Ludwig. And,” the agent added with what Beethoven thought was wholly unnecessary emphasis, “you would get paid.”


Beethoven flipped the phone shut. He hated cell phones. Every year they got smaller and, he felt, quieter, and the satisfaction he used to get from slamming the handset down on the receiver of his landline was forever gone from his life. He looked at his ersatz coffee filter, opened it up, shook off the grounds and smoothed it out. A vision of a shaggy Highland cow danced through his mind. No, he thought, no bagpipes! Scotland, cows, stupid censors, beer. He mused about the last rave he played at. One of the gilded cosmopolitan hipsters busted some nice moves that he said came from Edinburgh by way of Paris—“Ecossaises,” the guy called it. The music was stupidly simple. A cow could dance to it.


To hell with it, he thought, this is for beer. Beer, beer, beer. He got out a piece of manuscript, set the timer on his cell phone for fifteen minutes, and wrote in a 2/4 time signature.



Saturday, August 21, 2010

Noise

Every couple of weeks I get a phone call from pollsters who say they want to know my views about radio stations or stores or political candidates. Hard though it may be on my ego, the pollster really doesn’t care about my personal views about these things. The pollster is interested in the average views of the population, and my views are a fraction of a percent of that bigger picture. A minimal knowledge of statistics will tell you that such census data can lead to error if you try to predict individual characteristics from the averages of a population. Very few families actually have 2.2 children, or 1.7 cars.

Despite this, microbiologists have relied on averages from census data for decades. Really, most of our understanding of the cell is based upon taking the output of trillions of cells, and making a picture of an imaginary “average” cell. There are practical reasons for this, mainly, the difficulty of measuring femtograms (10-15 grams) of product or proteins that are present in only a couple of copies per cell. As we'll see, there are good scientific reasons as well.

I am interested in studying gene expression—how genes in DNA get transcribed to make a messenger RNA, and how that RNA gets translated to make a functional protein that does stuff for the cell. I have never looked at how an individual bacterial cell does this. I have always studied trillions of cells. If a gene is being highly expressed, this isn’t a problem. A gene could be transcribed on average a hundred times per minute per cell—a cell-to-cell variation of five transcripts per minute is negligible. But many genes are weakly expressed, transcribed on average once every half hour. Now cell-to-cell variation becomes an enormous factor: one cell could transcribe a gene four times in one hour, another cell not at all in the same time.

These differences become more pronounced as we follow the process of gene expression. The product of transcription, messenger RNA, persists in the cell for only a few minutes, during which it can be translated a dozen times. The protein that is produced by translation is generally stable, and persists for over an hour. So, in the previous example where one cell has transcribed a gene four times in an hour while another hasn’t transcribed it at all, the first cell could have hundreds of copies of the resulting protein, while the second cell will have none. The average, in this case, is completely unrepresentative of either real cell.

Recently, thanks to innovations in microscopy and biotechnology, it’s become possible to examine transcription and translation in single bacterial cells. We can now get past the distortions of the “average” cell, and see how real cells express genes.

First off, expressing a gene requires transcription: making an RNA copy of the gene’s DNA. The presence of a specific RNA within a cell can now be detected by using a fluorescent dye attached to a short snippet of DNA that will specifically attach to the RNA in question. If the RNA is present—if the specific gene has been transcribed—the cell containing it will glow, and if the RNA is not present—the specific gene has not been transcribed, or the RNA has decayed—then the cell will not glow. This method is sensitive enough that we can tell the difference between cells with one or two or ten copies of the RNA by measuring differences in how brightly the cells glow.

Second, expressing a gene requires translation: making a protein using the instructions in the RNA. To see when protein was made, researchers use a clever trick (a trick whose invention won the Nobel Prize). As the protein of interest is made in the cell, it gets combined with a molecule of a protein called “Yellow Fluorescent Protein”, or YFP. True to its name, YFP glows yellow, so more of the specific protein means a brighter, yellower cell. Just like with RNA, this yellow glow can be measured, indicating anywhere from a few copies of the specific protein to thousands of copies.

These techniques had already been used to examine expression of single genes in a cell; in a new study, researchers examined expression of over a thousand genes in single cells of the common bacterium E. coli. To do this, they used a over a thousand different lineages of E. coli, each with one gene modified so its protein would be attached to YFP. They then built a special microscope slide that would send each of these bacteria past a detector, one by one, over and over again. This is amazing. It was all done robotically—moving the cells, counting the cells, measuring fluorescence, calculating the number of fluorescent RNAs or proteins per cell, everything—at about 8,000 cells per minute.

Their data is more reassuring than it is surprising; this paper is more of a technological tour de force than a leap into the unknown. They confirm that a completely “average” cell is no more a reality than a completely average human. Instead, the number of copies of each protein per cell varied according to a mathematical distribution. Some proteins are well represented, with thousands of copies per cell, others a scarcely found in any cells at all:

The “average” cell has 500 copies of the Adk protein, 300, copies of the AtpD protein, and 1 copy of the YjiE protein. But, less than one cell in 10 is average for the Adk or AtpD proteins, and only a third of cells are average for the YjiE protein.

It’s unlikely for a cell to be “average” for even a single trait, much less for every trait. The tendency to be different from average is technically called “noise,” and what the researchers found was that for relatively scarce proteins (less than about 10 copies per cell, such as YjiE), less expression meant more noise. For very rare proteins, there was enough noise that the idea of an “average” cell became meaningless. Interestingly, with more common proteins, noise didn’t diminish as proteins became much more common. Rather, the noise became a constant:

These results provide a useful reminder for microbiologists assaying trillions of cells (as well as for telephone pollsters trying to tap the pulse of the populace). The large population of bacteria I experiment upon may be genetically identical. However, their protein composition is extremely diverse. This means that the individuals in a large, genetically identical population will respond differently to their environment, and could conceivably start down completely different evolutionary paths as a result. This is all due to noise in gene expression, which is ultimately due to the chance events of molecules bumping into each other.

There is another useful reminder in these results, and paradoxically it has to do with the great value of that mythical average. Remember that expressing a gene requires transcription, to make a molecule of RNA. For a specific gene, this can happen frequently or rarely. Then, the RNA must be translated to make a protein, which will last for hours. A single RNA can be translated dozens of times, but most RNAs spontaneously decay within a couple of minutes. Thus, it’s quite possible to find a cell that has transcribed a gene to make RNA, and that RNA has been translated to make protein—and after a few minutes, the RNA has all decayed, but the protein is still around. This study found plenty of such cases; the data for one is shown here:

Each dot in this picture represents the RNA and protein for a single gene in a single cell; the cell represented by the dot with a square around it had 10 copies of the RNA from this gene, and two thousand copies of the protein. The cell represented by a dot with a circle around it had no copies of the RNA from this gene—they had all decayed—but nearly ten thousand copies of the protein. In individual cells, there is no—zero—correlation between RNA and protein.

The concept of gene expression requiring transcription and then translation to go from information in DNA to functional protein is fundamental to our understanding of biology—so much so that it is referred to as the “Central Dogma of Biology.” It is also a concept that would be completely unattainable if one only had this sort of data from individual cells. It’s only by looking at the averages that we can see these general themes. Indeed, for someone who makes a living teaching the central dogma, it’s reassuring to see this graph, comparing average levels of specific RNAs and their corresponding proteins over thousands of genes in thousands of cells:

The central dogma works! There is a correlation between RNA and protein!

So census data that averages out the characteristics of millions is useless for understanding individuals, but essential for understanding underlying truths. Data squeezed out of a single individual tells you the state of that individual, but can be misleading when used to derive underlying truths. This applies to bacterial cells and voters and consumers alike.

This notion has another application, one close enough to home to give me pause. The bacteria used in this study were genetically identical. Noise, ultimately traceable to the random jiggling of molecules in the cell, took this genetically identical population of bacterial cells and made them into a widely diverse population, each behaving in a unique, idiosyncratic manner. The same thing happens in your brain. A thought is no more than the ebb and flow of chemicals between trillions of genetically identical neurons. We can take the average behavior of all neurons, and predict that a certain stimulus will lead to a certain response in an individual cell. But noise has veto power over this program. What I do, what I think, what I think of as my personality—the noise of random collisions between molecules leaves its mark on all of these.


Yuichi Taniguchi, Paul J. Choi, Gene-Wei Li, Huiyi Chen, Mohan Babu, Jeremy Hearn, Andrew Emili, X. Sunney Xie (2010). Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells. Sicence 329: 533-538.

Friday, August 20, 2010

Friday Flora: It's still Friday in Hawaii edition

From the recent trip to Spicer Meadows Reservoir, a bit of an aspen:And for bonus, a panoramic view of the Dardanelles from the campsite. Click on it to make it bigger, then get up close to the screen to capture the you-are-there experience.

Tuesday, August 17, 2010

Vexation

I don't really like the science coverage on BBC radio. The Beeb may be good for some things, but they tend to take the most breathless university press releases (already a pretty bad source of information) and somehow make them even more breathless.

The latest example came over the wireless tonight. I paraphrase, but the words in bold were used in the report: "Scientists confirm that woolly mammoths went extinct because of climate change, not human predation. The issue had been in doubt, but a team of researchers at [English University] proved that that climate change was the culprit. Using computer models, the researchers showed that warming trends at the end of the ice age would have replaced the mammoths' preferred forests with grassland."

Just in case any of the editors at the Beeb are reading...

Dear sirs/madams: a computer simulation, based on incomplete data, is not proof of what happened 16,000 years ago over a large, diverse, and multifactorial habitat. It may be useful to generate certain hypotheses, but that's all. I would happily welcome you into my introductory biology class, in which it seems you could learn something.

Monday, August 16, 2010

Turkey update


They're still hanging around the neighborhood, living of the fat of the land. The hens move with stately grace, pausing every now and then to delicately strip some grass of its seeds. They'll use their beaks to gently grab a stem just below the seed head, then pull up with their beaks, shucking all the seeds straight into the gullet. The chicks have not yet learned to move with such grace. They bumble.

Monday Musical Offering

Another Dvorak Humoresque--Opus 101 number 4.

Dvorak was a violist, not a pianist. Each of these Humoresques has two measures that just don't work on the piano. The fingers get tangled up, or a jump is too awkward, or one must play two-against-three in one hand. But, I complain needlessly. They're 99% fun and as tuneful and cheerful as you can hope for.

Friday, August 13, 2010

What is fair, revisited

A while ago, I noted a paper that tracked the evolution of views of fairness with development in children. The paper noted that the percentage of "libertarian" children remains constant, and I suggested perhaps developmentally stunted. It seems somebody else may have read that paper, and came up with something much more amusing. Go read.

Friday Flora

It's a double header! The trip to mountains gave me a lot of photos. First, a scenic buckwheat:
Second, a bladderwort that I found in a marshy spot near Sword Lake. I've always liked bladderwort. It's a carnivorous plant. Each of the little blobs is actually a spring-loaded sac. If an unfortunate animalcule swims up to the sac and brushes up against a trigger hair, the sac springs open and sucks the victim in. Very cool. Be sure to click on the picture twice to see it extra big.


Thursday, August 12, 2010

At least it's not a tattoo

Having just survived a rather hairy summer session, I made my way to the barber shop (three chairs, no waiting). The first chair, manned by the weirdly-bearded old surfer dude, was occupied by an older man who was being made to look more distinguished. The third chair, manned by the clean-cut young mountain biker, was occupied by a young Asian-american who was working on making his spiky hair even spikier. He was very particular about it, and the result was not so much a simple haircut, but a continuous dialog between barber and client, punctuated by an occasional snip snip snip. The second chair, manned by a new guy, was open, so I took it.

Halfway through my haircut, the third chair was vacated. It was soon occupied by a nine(-ish) year old boy who was waiting patiently with his mom. As he trundled over to the chair, he presented the barber with a printout from a computer, and said with a mixture of shyness and bravado, "make it like this:"
To his credit, clean-cut young mountain biker set to quite professionally, without the snicker that I would have been unable to suppress. I didn't stick around to see the result, but I was thinking that the mom would surely take a picture of the boy--and that she would have potent blackmailing ability in a few years.

Wednesday, August 11, 2010

Protein Origami

So, imagine taking a long string, shaking it around, and having it spontaneously snap into this shape:

There’s an amusing article in the New York Times about a “crowdsourced” solution to what is called the “protein folding problem”. Every different protein has a unique three-dimensional shape, and the proper function of every different protein is dependent upon that specific shape. Proteins are like long flexible strings of beads, where each bead is a different amino acid. The strings of beads acquire the shape critical to their function by folding up into curlicues and clumps, held together by a large number of very weak bonds between the beads. Different proteins have different shapes because they have different arrangements of beads, with subtly different interactions. We know the linear sequence of amino acid beads in thousands of protein strings; the “protein folding problem” is using this two-dimensional, linear knowledge to predict exactly what three-dimensional shape the string will fold up into.


The high-powered way to solve this problem is to build bigger and bigger computers that can keep track of the one-to-one interactions of hundreds of amino acids. A lot of power is required, since the number of interactions is a factorial function of the number of amino acids, and a typical protein has hundreds of amino acids. The crowdsourced solution to this problem is to farm it out to thousands of bored computer gamers; by making it into a addictive video game, you get people to do the same thing (click here for the game, and a more detailed intro to protein folding. Don’t say you weren’t warned). The supercomputer, the gamer, and the living cell all do exactly the same thing: try out trillions of different arrangements of atoms, and see which ones are the most stable. The supercomputer thinks its deep thoughts, while the gamer clicks a mouse to drag atoms around on a screen trying to get a good score. The living cell makes its string of amino acids, and random thermal motion jiggles the string around until it finds ever more stable states.


Thermodynamics has been called “the science of desire,” a way of understanding what the universe wants. Basically, the universe’s overwhelming desire is to shed as much energy as possible. As anyone who has tried to keep a house and garden tidy, order does not usually emerge from chaos without a significant input of energy. Usually, the universe wants disorder, and making a complicated structure—whether a garden or a cell or an elaborately folded protein—requires the input of energy. The descent into chaos is spontaneous, ardently desired by the universe, since it represents that energy leaving the system.


However, there’s another way that energy can leave a system. Remember, the universe wants everything, proteins included, at an energetic minimum. Put two positively charged amino acids in a protein too close together, and the protein’s got too much energy stored in it, like a compressed spring. Separate two amino acids that want to stick together, and there’s too much energy stored in it, like a stretched out rubber band. These intramolecular forces are minimized in a properly folded protein.


So really, the universe’s desire can be met two different ways. Energy could leave the system by increasing chaos, or it could leave the system by relaxing intramolecular forces. If lots and lots of energy leaves a system by relaxing intramolecular forces, then that will satisfy the universe’s desires enough that it will tolerate an increase in order. This is why proteins can fold spontaneously, and why ordered structures such as crystals can form without the input of energy.


A beautiful case of spontaneous order-from-chaos was recently seen in a type of bacterial protein called a porin. These are proteins that sit in the outer membrane of the cell and act like a pore in one’s skin. They allow the passage of material into and out of the cell, and occasionally modify things as they move through. Porins are also absolutely lovely to look at. Imagine a single ribbon of over 200 beads spontaneously arranging themselves like so:

This structure is called a beta-barrel. The cell starts with an unstructured string of amino acids (1); intramolecular attraction will start to bring individual amino acids together to form a sort of a two-dimensional zig-zag (2). The zig-zag is essentially a two-dimensional sheet (3 and 4), which can be curled around to make a barrel (5).

It’s a bit of an oversimplification to say that this folds up on its own without any help. No energy is required, true, but there are few enzymes that are necessary to help it achieve this shape. Proteins that sit in the membrane are in an “oily” environment, and the amino acids on their surface must also be “oily.” However, these proteins are made in the inside of the cell, a watery environment—and oil and water don’t mix. So, in folding these proteins, a couple of problems must be overcome. First, an oily protein must be made stable in water. Second, it has to be transported to the appropriate membrane, and only then allowed to fold. There are specific enzymes to help with each step. However, the identity of these helping remained uncertain. There were lots of candidates. A group at Harvard led by Daniel Kahne came up with an ingenious solution to sorting the enzymatic wheat from the chaff.


Kahne’s group started by using a porin that allowed molecules into the cell and cut them in half as they moved through. Then, they fed this porin a molecule that emitted light when it was cut in half. So, if the porin was folded up properly—if it had received all the necessary help from all the enzymes along the way from the inside of the cell to the outer membrane—it could easily be detected by flashes of light as it worked. Finally, instead of working with intact cells, they worked with little blobs of membrane. The enzymes suspected of helping out with the porin folding process could then be added, one by one, to these blobs of membrane. If the right combination of enzymes was present, there was light as the porin cut up its work. If the right combination of enzymes was absent, the porin would never fold up properly, never cut up its target, and there would be no light.

Kahne’s experimental system: the porin (red can) is embedded in a bleb of membrane. It cuts a target molecule as it moves it into the bleb, and causes it to emit light. Unfolded porin protein, along with various helper enzymes, can be added to this system.


One essential enzyme actually had the job of preventing the porin from folding. This enzyme is called a “chaperone,” as it escorts the unfolded protein as it goes from the inner membrane to the outer membrane. Without this protein, the porin tried to fold up before it got to the membrane—so, no light.

Once the unfolded porin protein was delivered to the membrane blob (or, presumably, to the outer membrane of the cell), an additional five enzymes were required. These enzymes are permanently attached to the outer membrane, and without any one of them, Kahne’s group saw no light from the activity of the properly-folded porin. No other proteins originally suspected in the folding of the porin were required. Also, no energy was required—no chemical energy from ATP, no potential energy in the form of a voltage difference across the membrane, nothing. The process is truly spontaneous.

Presumably, this is what is going on in the cell: The chaperone proteins (pink hexagons) coat the unfolded protein, preventing oily amino acids from interacting with the water environment between the inner and outer membranes. The chaperones also deliver the unfolded protein to some helper enzymes (blue squares and rectangle), which allow the unfolded protein to spontaneously fold into a working porin (red drum).


So what do those five proteins do to help the porin fold? As the authors of this study write, “Together, [these proteins] perform a chemical transformation that we do not understand…” Presumably, some of them must receive the unfolded protein from the chaperone proteins, while others must insert the unfolded protein into the membrane, and perhaps feed it in slowly enough that it can fold bit by bit. The energy to do this probably comes from the formation of the intramolecular bonds that hold the beta barrel together. We don’t know how these enzymes work, but knowing their structure might give us some clues--perhaps we can get some gamers to work on them. In the meantime, it's wonderful to think about a jumbled string spontaneously becoming such a beautiful structure as a beta barrel.


Chrisine L. Hagan, Seokhee Kim, and Daniel Kahne (2010). Reconstitution of Outer Membrane Protein Assembly from Purified Components. Science 328 890-892.

Monday, August 9, 2010

Away for a few days

No Monday Musical Offering (again...they will resume next Monday), nor much else going on here for the last few days. I took the weekend off to go canoeing at Spicer Meadows Reservoir with M. A good antidote to the summer teaching schedule. I felt like a balloon that had been blown up too full, then let go phbhthfhbhfhthvhbhbh!

Much better now.

Saturday, August 7, 2010

Tie dye class

The day after the final, I taught a tie-dye class at the UC Davis Craft Center. Four students, not 140, and a lot more casual. But still, it's teaching--I found myself doing a lot of the same sort of things, trying to get learning by participation, etc. The students were representative too. I didn't dye any t-shirts; I decided to replenish my snotrag supply, which was starting to fall apart. I just got around to washing the results. As usual, some winners and some losers--and they will all work just fine for catching snot. No doubt where the snot goes on that one on the lower left.

Friday, August 6, 2010

Thursday, August 5, 2010

Yes, but how many ATP are produced by the Krebs cycle?

The intro Bio class is finally over; grades are handed in, email from students wondering if 69% is good enough for a C has dwindled to a trickle, and I am not obligated to do a lick of work for the class today. It is a relief. However, as it has dominated my life for the last 5 weeks, I am still churning it over.

There was a question I almost asked the students for the final, but I shied away from it. It was something like this:

“You are made mainly of atoms of Carbon, Hydrogen, Nitrogen, and Oxygen. You are an organoheterotrophic animal; before that, you were a plant. Before that, you were atmospheric gases and water. Before that, you were a star. Explain the processes behind each of these transitions.”

Way too poetic for a final. The ESL students would be utterly lost, and those students who hate Hate HATE to use their own imagination would not be able to figure it out. But it’s a question I wish my students would want to answer. On a practical level, it requires understanding energetics, autotrophy, some chemistry and the history of the Earth and the Universe. But what I really wish is that my students would get the poetry of life.

I’ve heard a religious experience described as seeing beyond the visible world. The curtain is lifted, so that you can see the cogs and gears and mechanics that actually move the world, and there’s no more mystery. You understand the miracle of day-to-day life, and you know how things connect. This is what I wish I could lead all of my students to see.

With religious experience, the curtain is lifted for you—whether by the divine or by a fluctuation of neurochemicals, I won’t say. However, with biology, the student has to put in some hard work to part the curtains. But if the student is on top of it, they’ll consciously breathe an atmosphere that is literally the result of a single genetic boo-boo some three and a half billion years ago. They’ll feel their bodies and feel atoms that were snatched out of the atmosphere by plants. They’ll feel atoms made of hydrogen fused into heavier elements in long-dead stars. Science is necessary to part the curtain of “ordinary” life, but behind that curtain there is delicious poetry.


How they grow

A week after they last visited our yard, Mama turkey and her three chicks came by again. The chicks have been busy growing...
We wondered how they got in and out of our yard. We knew the adults could fly well, but the chicks?
No problem.