Nobel Laureate: Roderick MacKinnon

 

The Nobel Prize in Chemistry 2003.

"for structural and mechanistic studies of ion channels"

Roderick MacKinnon (1956 - ) was awarded the 2003 Nobel Prize in Chemistry for his work on the the structure and mechanism of action of the potassium (K⁺) channel. MacKinnon shared the prize with Peter Agre who discovered water channels.

The presentation speech was delivered by Professor Gunnar von Heijne of the Royal Swedish Academy of Sciences.THEME:Nobel Laureates

Your Majesties, Your Royal Highnesses, Ladies and Gentlemen,

In the days of Alfred Nobel, the learned academies used to entertain and educate the public by holding open demonstrations explaining the latest scientific advances. This tradition has been largely – and perhaps unfortunately – forgotten. So let us try to revive the public demonstration of science, if only for a brief moment.

The demonstration I have in mind is a simple one, and only requires that you do something that is in any case particularly fitting for a Nobel Prize ceremony: to think. But only for exactly 5 seconds!

So, please start thinking, for 5 seconds ... Thank you!

Let us now reflect briefly on what has just happened, in each and every one of us. First, a sudden increase in the activity of the brain when you started to wonder what this is all about – should I really think at this point in the ceremony? – then, cascades of nerve signals when you were actually thinking, and finally a return to the normal resting state. And all this thinking ultimately relied on one of the simplest chemical compounds you can imagine: ordinary salt – sodium, potassium and chloride ions – streaming back and forth across the walls of your nerve cells, thereby generating the signals that activated your mind. And not even very much salt – a rough estimate is that the total amount of salt spent during these five seconds in each one of us was no more than a few grains. Only a fistful of salt to set a whole Concert Hall thinking!

And while all this brain activity was occupying our minds, our kidneys worked on quietly, as they always do, reabsorbing water from the urine to the blood. But in this case, the volumes of water transported are too big, even during five seconds, to be suitable for a demonstration from the podium.

This year's Nobel Prize in Chemistry is all about salt water, and the biochemical mechanisms that control where, when, and how often ions and water are let into or out of the cells in our body. Mechanisms that the two Laureates – Peter Agre and Roderick MacKinnon – have elucidated down to the atomic level.

Agre's was a "serendipity discovery": while working on a completely different problem, he stumbled across a protein in red blood cells that he could soon show was the water channel researchers had been looking for in vain for well over a century. His unexpected discovery opened a whole new field of study.

MacKinnon, on the other hand, decided at an early stage that he should try to do what was then thought impossible: to determine the three-dimensional structure of ion channels at atomic resolution. He bet his career on this vision – and succeeded to an extent that probably surprised even himself.

There is a lesson here, I believe: There is no one way to do science, and our support system must be sufficiently well funded and versatile to prepare the ground for both unexpected serendipity and focused, often risky, attacks on central scientific problems.

Peter Agre and Roderick MacKinnon stand for decisive contributions to the biochemistry of cell membranes, but their discoveries also have an almost tangible aesthetic component. Their work has uncovered an amazing "economy of design" in the atomic structures of the water and ion channels that is breathtaking in its simplicity and perfection. Indeed, after seeing these molecular machines, you find yourself thinking, "Of course, this is how it must be, this is how it must work!" What more could we ask of science?

Professor Agre, Professor MacKinnon, your fundamental discoveries concerning water and ion channels are singular achievements that have made it possible for us to see these exquisitely designed molecular machines in action at the atomic level. The biochemical basis for the transport of water – the most abundant and primordial substance of life – and ions – these tiny, mundane and yet absolutely essential constituents of the living world – can now be understood in unparalleled detail. On behalf of the Royal Swedish Academy of Sciences, I wish to convey to you our warmest congratulations, and I now ask you to step forward to receive the Nobel Prize in Chemistry from the hands of His Majesty the King.

---

Nuclear War Is Bad for You

 
A couple of scientists at the University of Colorado have modeled what might happen if there was a nuclear war between India and Pakistan [Regional nuclear conflict would create near-global ozone hole, says CU-Boulder study].

A limited nuclear weapons exchange between Pakistan and India using their current arsenals could create a near-global ozone hole, triggering human health problems and wreaking environmental havoc for at least a decade, according to a study led by the University of Colorado at Boulder.

The computer-modeling study showed a nuclear war between the two countries involving 50 Hiroshima-sized nuclear devices on each side would cause massive urban fires and loft as much as 5 million metric tons of soot about 50 miles into the stratosphere, said CU-Boulder Research Associate Michael Mills, chief study author. The soot would absorb enough solar radiation to heat surrounding gases, setting in motion a series of chemical reactions that would break down the stratospheric ozone layer protecting Earth from harmful ultraviolet radiation, said Mills.

Wow! That sounds really bad. By the way, they forgot to mention one other nasty little detail—about 100 million people will die in the blasts and of radiation poisoning in the aftermath of the attacks.

Sort of make an ozone hole seem insignificant, doesn't it?

---

The Bombardier Beetle

 
According to a report in ScienceDaily, there has been progress in understanding how the Bombardier beetle can eject such a powerful spray [The Bombardier Beetle, Power Venom, And Spray Technologies].

The bombardier beetle, found mainly in Africa and Asia, is remarkable in that it can fire a powerful jet of hot, toxic fluid to fight off predators such as birds and frogs. While the chemical reaction that makes the venom has been understood for some time, the actual power behind the venomous squirt, which can travel as far as 20cm, has been cause for speculation.

Quantities of hydroquinone and hydrogen peroxide gases build up in the beetle’s abdomen but, when necessary for defence, get mixed together in a connected ‘combustion chamber’ to produce toxic benzoquinone. This hot fluid is then fired off at force in the face of enemy predators.

Note, there isn't a problem understanding the chemical reaction and how the beetles control it. That's been well understood for several decades. You can watch a young Richard Dawkins debunking the standard creationst claims in a video posted on Genomicron [Bombardier beetles].

Ryan Gregory has followed this up with a more detailed posting that describes the evolution of bombardier beetles [Reducibly complex bombardier beetles]. Ryan was motivated to research this topic because one of the leaders of the University of Guelph creationist groups tried to use the bombardier beetle as evidence that evolution is impossible. I guess he didn't realize that this example has been refuted a long time ago.

---

[Photo Credit: Institute of Physics]

Two Non-Scientists Talking about Science

 
Listen to Dr. R.C. Sproul interview Ben Stein. There are lots of very funny bits but let me pick out just one example. Here's what Ben Stein says about scientists ... (around 15 minutes)

People go into academic life in large measure because they're frightened people. They want a kind of sanctuary and uh ... so when they're attacked, or questioned even, they react very, very strongly. They're scared people, and they're really scared of Intelligent Design [Creationism] because if Intelligent Design [Creationism] is true, and if, in fact, Darwinism is ... only goes so far and only covers a small amount of the territory, all kinds of threat to their power and status arise.

Hmmmm ... I wonder why we call them IDiots?

---

[Hat Tip: Evolution News & Views]

Have Your Cake and Eat It Too.

 
Matt Nisbet has tried to defend his attacks on PZ Myers and Richard Dawkins with a posting that promotes Paul Kurtz as a "reasonable" atheist [Paul Kurtz: The Local Leader Who Happens to Be an Atheist].

He followed it up with a posting on his comment policy where he notes that he has been forced to delete some of the comments from people who defend PZ Myers and Richard Dawkins [A Note On Comment Policy]. In that comment thread, Matt Nisbet defends his position on framing ...

I've been very active in communicating why my research is worth the money and I have done it very effectively.

-->I've done close to three dozen presentations over the past year and talked face-to-face with several thousand scientists, policymakers, other academics, students, and lay citizens.

-->I regularly post here on the relevance of framing to a range of topics. The top tabs of the blog explain in depth the nature and application of research to science communication.

-->I've done about 40 media interviews on issues related to science communication and/or framing.

-->I followed the Science article with an article at the WPost, a longer cover feature at The Scientist, both articles I link to as PDF copies free for reading. I have also done extended interviews on the topic at the Point of Inquiry podcast.

-->I advise and consult with a range of nonprofits, organizations, and government agencies.

-->I engage almost every serious minded blog post and comment with a respectful, and usually detailed reply.

Here's the problem. Matt Nisbet is promoting the concept of framing science. This is his field and he has every right to do that. I don't buy it and neither do many other scientists who think that framing is too close to "spin."

But that's not all that Matt Nisbet wants to do. Not only does he want scientists to adopt framing as a means to communicate science but he also wants to dictate the frame! In other words, he sets himself up as not only an expert in communication but also an expert in what should be communicated in the rationalism vs superstition debate. He can't tell the difference between the concept of framing, which many scientists reject, and his personal opinion, which is that vocal atheists are hurting the cause of atheism.

Matt want to have his cake and eat it too. He will get neither.

---

[Photo Credit: Worst Birthday Cake .. Ever!]

Monday's Molecule #67

 
This is a very important protein. Most living organisms on this planet could not survive if this protein didn't do its job.

Your task for today is to identify the protein (1) and the species from which this particular protein was isolated (2). You also have to describe the function of this protein (3).

In addition you have to identify the Nobel Laureate who was awarded a Nobel Prize for—among other things—working out the structure of this protein. Note that the protein is a tetramer (quaternary structure) showing a nice example of a helix bundle.

The first person to correctly identify the protein, species, and function, and name the Nobel Laureate. wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize. There are two ineligible candidates for this week's reward.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly answers the questions and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureates so you might want to check the list of previous Sandwalk postings.

Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: We have a winner! Matthew Sekedat of Rockefeller University knew that this molecule was the potassium pump from the bacterium Streptomyces lividans. The protein is responsible for pumping potassium ions across the cell membrane. The Nobel Laureate is Roderick whose lab solved the structure of the protein.

---

TV Ontario's Best Lecturer

 
I've been critical of the contest for best lecturer because it focuses on style and not on substance [TV Ontario's Best Lecturers]. A few months ago I posted the names and areas of expertise of the three judges. Here's who they picked.


You can see the winning lecture at Ontario's Best Lecturer 2008!. A lot of it discusses naturalism and supernaturalism. Listen for yourself and see if you agree with the judges selection.

---

Framing Atheism

 
Here's a video that presents statistics about atheism. Some of it makes me uncomfortable because the numbers can be very misleading. Is this an example of framing according to the ideas of Nisbet and Mooney? If so, to my mind it illustrates all of the bad things about framing that turn scientist off.

---

[Hat Tip: Friendly Atheist]

Free Cheesecake!

 
Canadian Cynic just recorded one million page views! Congratulations to whoever you are and to your equally mysterious co-bloggers. The blog is promising free cheesecake for everyone [ Cheesecake for everyone] but the catch is you have to find them first.

BTW, take a look at the statistics posted on the Canadian Cynic website. The average length of each visit is almost 6 minutes!!! This is a long time for most blogs. (It's about 1.5 minutes on Sandwalk and 26 seconds on Pharyngula.)

I wonder if the average visitor to Canadian Cynic is temporarily stunned by the language? Or perhaps by the stupidity of the blogging Tories?

---

One Protein - Two Folds

Michael Clarkson at Discount Thoughts posted a discussion of a paper published by Tuinistra et al. (2008) [Two folds for lymphotactin]. The interesting thing about this paper is that it describes a protein (the chemokine lymphotactin) that can adopt two very different folds under physiological conditions.

This is an exception to the general principle that a protein will adopt a single thermodynamically stable three-dimensional structure. Here's how Micheal Clarkson describes it ... (Please read his article.)
THEME:

More posts on
Protein Structure

This is an interesting and important finding because it is (so far) the only example of a protein adopting two completely different stable folds with no hydrogen bonds in common at equilibrium. Trivially, natively disordered proteins adopt multiple conformations under physiological solution conditions, and many proteins alter their conformations in response to ligand binding while keeping most of their hydrogen bond network intact. In this case, however, an existing network of stabilizing bonds is completely disrupted in order to form a new fold with a totally different function. I've already discussed some of the implications of this with respect to protein folding, and in regards to the recent transitive homology studies out of the Cordes group. Lymphotactin offers lessons and ideas for protein folding and evolution that must be taken into account. In particular, the fact that point mutations can significantly stabilize one or the other of these structures implies that there may be previously unsuspected shortcuts through structural space between folded states that avoid unproductive or energetically unfavorable molten globules.

In addition, these results signify that the Anfinsen paradigm that dominates our understanding of protein structure ought not be taken for granted.¹ In many cases it is true that a peptide sequence uniquely determines a single structure under all physiological conditions. Of course we have known for some time that certain peptide sequences do not produce ordered structural ensembles at all. What the lymphotactin example makes crystal clear is that a given sequence can yield an ensemble with multiple energetic minima that reflect related but topologically distinct structures. Tuinstra et al. suspect that this phenomenon has not been noted previously because structures of this kind would not be amenable to crystallization, or would only crystallize in one (of many) structures. If this is so, then as more and more proteins are studied using solution techniques under physiological conditions we may find multiple structural minima in a variety of proteins. Such discoveries may significantly enhance our understanding of the protein regulation, function, and evolution.

Why is this important? Because this example demonstrates that getting from one type of fold to another type of fold isn't as big a problem as most people think.

The key phrase in Michael Clarkson's explanation is, "In particular, the fact that point mutations can significantly stabilize one or the other of these structures implies that there may be previously unsuspected shortcuts through structural space between folded states that avoid unproductive or energetically unfavorable molten globules." As we will see, the Intelligent Design Creationists argue that it is impossible to evolve from one type of protein to another, therefore God must have done it.

Incidentally, it's worth noting that some proteins adopt different conformations when they bind to other molecules (the target they bind to is called a "ligand" and it could be DNA, another protein, or a small molecule like ATP). Michael Clarkson mentions this—he appears to be a pretty knowledgeable guy—but I just want to repeat it so that everyone understands. The idea that parts of a protein (motifs, domain) can change folds under certain conditions isn't new.

---

1. I would prefer to say that, like all general concepts in biology, there are exception to the Anfinsen paradigm. I don't believe there are any fundamental concepts that don't have exceptions. That's the nature of biology, and evolution.

Tuinstra, R.L., Peterson, F.C., Kutlesa, S., Elgin, E.S., Kron, M.A., and Volkman, B.F. (2008) Interconversion between two unrelated protein folds in the lymphotactin native state. Proc. Nat. Acad. Sci. (USA) 105:5057-5062. [doi: 10.1073/pnas.0709518105]

Levinthal's Paradox

Back in 1969, Cyrus Levinthal was thinking about protein folding (Levinthal, 1969). He wondered how long it would take for a protein to fold correctly if it had to sample all possible conformations in three-dimensional space.

THEME:

More posts on
Protein Structure
Imagine that there was only a single bond between each amino acid in a protein of 101 amino acid residues. Imagine that there were only three possible configurations around each of those bonds. This means that the protein could adopt 3¹⁰⁰, or 5 × 10⁴⁷ different conformations.

If the protein is able to sample 10¹³ different bond configurations per second then it would take 10²⁷ years to sample all possible conformations of the protein (Zwanzig et al. 1992). This is quite a long time. Far longer, in fact, than the age of the universe.

Small proteins usually fold spontaneously within seconds and even the largest proteins fold within minutes. The difference between the theoretical calculation and the observed result is known as Levinthal's Paradox.

It isn't really a paradox. Levinthal knew full well that proteins did not fold by sampling all possible conformations. He knew that protein folding involved local cooperative interactions such as formation of α helices and that the formation of such secondary structure elements proceeded in parallel and not sequentially as his thought experiment proposed.

We now know that protein folding is largely driven by hydrophobic collapse as the regions of secondary structure come together to exclude water. This process is a global process involving simultaneous rearrangements of hundreds of bonds at the same time. That's why proteins fold so rapidly. Cyrus Levinthal knew this.

The point of Levinthal's paradox is to demonstrate that when a mathematical calculation shows that some routine process is impossible, then it's the calculation that's wrong, or the assumptions behind the calculation. This point is lost on most Intelligent Design Creationists. They are tremendously fond of complex calculations proving that some biological process is impossible. To them, this is not proof that their calculations are flawed—it's proof that a miracle occurred.

---

Levinthal, C. (1969) How to Fold Graciously. Mossbauer Spectroscopy in Biological Systems: Proceedings of a meeting held at Allerton House, Monticello, Illinois. J.T.P. DeBrunner and E. Munck eds., University of Illinois Press Pages 22-24 [complete text]

Zwanzig, R., Szabo, A. and Bagchi, B. (1992) Levinthal's paradox. PNAS 89:20-22. [PNAS]

Michael Egnor Gets It Right

 
Michael Egnor has posted a number of quotations from me about how I would deal with people who don't understand the basic principles of science [Dr. Larry Moran and Censorship of Intelligent Design].

He get it mostly right. If they are undergraduates who don't understand that evolution is a scientific fact, the Earth is 4.5 billion years old, and humans share a common ancestor with chimpanzees, then they flunk the course. If they are graduate students in a science department, then they don't get a Ph.D. If they are untenured faculty members in a science department, then they don't get tenure.

Readers might be amused at Michael Egnor's comments regarding Kirk Durston. It's further proof that IDiots are irony deficient. (Note that Kirk has not accepted my invitation to give a seminar here in the Biochemistry Department. I guess his "courage" has limits.)

Why should Mr. Durston’s willingness to present his scientific evidence for intelligent design to other scientists require courage? Isn't the presentation of evidence a routine part of science? Why should presenting evidence for intelligent design put Mr. Durston’s "scientific reputation on the line"?

Are you listening Kirk? Michael Egnor M.D. wonders why you don't come here and defend your evidence that protein folding demonstrates the existence of God.

I gave you two dates last November: you can give a seminar on Tuesday April 22nd or Tuesday April 29th.

---

Mike Huckabee Promotes "Expelled"

 
Were you wondering what Mike Huckabee was up to these days? No? Okay, then you probably won't be interested in this video ....


Why is there such a strong correlation between being stupid and believing in the Bible? How can a man like Mike Huckabee be seriously considered as a candidate for "leader of the free world?"

---

[Hat Tip: friend fruit]

Buy This Book!!!

 
Carl Zimmer is among the very best—possibly the best—of the modern science writers. His new book Microcosm: E. coli and the New Science of Life is going to be on sale May 6, 2008. Buy it, now. I just did.

Here's a synopsis from Publishers Weekly.

When most readers hear the words E. coli, they think tainted hamburger or toxic spinach. Noted science writer Zimmer says there are in fact many different strains of E. coli, some coexisting quite happily with us in our digestive tracts. These rod-shaped bacteria were among the first organisms to have their genome mapped, and today they are the toolbox of the genetic engineering industry and even of high school scientists. Zimmer (Evolution: The Triumph of an Idea) explains that by scrutinizing the bacteria's genome, scientists have discovered that genes can jump from one species to another and how virus DNA has become tightly intertwined with the genes of living creatures all the way up the tree of life to humans. Studying starving E. coli has taught us about how our own cells age. Advocates of intelligent design often produce the E. coli flagellum as Exhibit A, but the author shows how new research has shed light on the possible evolutionary arc of the flagellum. Zimmer devotes a chapter to the ethical debates surrounding genetic engineering. Written in elegant, even poetic prose, Zimmer's well-crafted exploration should be required reading for all well-educated readers. (May 6)

Copyright © Reed Business Information, a division of Reed Elsevier Inc. All rights reserved.

---

Having a Wife Creates More Housework for Men

 
A newly released study looks at the amount of house work done by men and women in different living situations. Like most of these surveys, the data is based on interviews and on diaries kept by men and women. The most remarkable results are reported in a press release from the University of Michigan [Exactly how much housework does a husband create?].

Here's how they describe the data collection process.

For the study, researchers analyzed data from time diaries, considered the most accurate way to assess how people spend their time. They supplemented the analysis with data from questionnaires asking both men and women to recall how much time they spent on basic housework in an average week, including time spent cooking, cleaning and doing other basic work around the house. Excluded from these "core" housework hours were tasks like gardening, home repairs, or washing the car.

Assuming that this is a reliable way of accessing workload, the study published a chart showing the amount of housework done by maried and single men and women.


The 2005 results show that when women get married they end up doing 7 hours more housework per week but when men get married they end up doing 8 hours more housework per week. The take-home message is clear. Women are a lot more costly than men. Women do more to mess up a house than men do.

Pay attention, men. It may not be worth the effort to get married.

The title of the press release is interesting: Exactly how much housework does a husband create?. Here are the opening paragraphs.

ANN ARBOR, Mich.---Having a husband creates an extra seven hours a week of housework for women, according to a University of Michigan study of a nationally representative sample of U.S. families.

For men, the picture is very different: A wife saves men from about an hour of housework a week.

The findings are part of a detailed study of housework trends, based on 2005 time-diary data from the federally-funded Panel Study of Income Dynamics, conducted since 1968 at the U-M Institute for Social Research (ISR).

Is it just me or does there seem to be a disconnect between the statements in the press release and the chart that's published on the same page?

---