Nobel Laureates: Richard Axel and Linda B. Buck

 
The Nobel Prize in Physiology or Medicine 2004.

"for their discoveries of odorant receptors and the organization of the olfactory system"

Richard Axel and Linda B. Buck won the Nobel Prize for discovering olfactory receptor genes. They showed that mice have about 1000 different olfactory receptor genes, each one encoding a different receptor.

You can watch a video recording of the acceptance speeches or read them as PDF documents [Axel Lecture][Buck Lecture].

Oh My God!

 
This is a photograph taken by Zarna, one of my students who just came back from a trip to India.

The Difference Between Rationalism and Superstition

 
Bill Dembski's Comments About Comments.

I don’t plan on policing or editing comments. If you post a comment that I don’t think is productive, I’ll probably not just eliminate your comment but you from this blog (which, given the way WordPress handles comments, means all your comments will be removed). So if you have any doubts about whether I’m going to react negatively to your comments, back them up — I won’t. Note also that I’ve had it happen where someone ingratiates himself with me and then turns. Bait and switch is a sure way to be banned from commenting here.

My policy on comments: anyone can post whatever they like, especially if they disagree. There will be no censorship of ideas on Sandwalk.

Darwin's Grave

 
Mike Dunford visited Westminster Abbey today and stood at the place where Charles Darwin is buried. He wonders what an agnostic should do under those conditions. See A Strange Moment.

Here's a photo of Darwin's final resting place in Westminster Abbey.

A Sense of Smell: Olfactory Receptors

 
The sense of smell in vertebrates is mediated by proteins called olfactory receptors (OR). In the case of mammals, these proteins are embedded in the membranes of sensory neurons in the nasal cavity. Each neuron is thought to contain a single type of olfactory receptor responding to a single type of odorant.

When an odorant binds to the outside of the olfactory receptor it transmits a signal to the interior of the cell. This signal triggers a response that excites the neuron and causes it to pass a message back along the axon to the brain. The brain then interprets the excitation as a specifc odor.

Olfactory receptors belong to a class of proteins called G-protein coupled receptors (GPCR). These proteins possess a characteristic bundle of seven membrane-spanning α-helices forming a tube within the membrane. The binding site for the specific odorant is located within the tube.

It has not been possible to crystallize any of the GPCR's that have been identified but the structures of some similar proteins are known. This enables workers to predict the structure of olfactory receptors using computer models. The models are then tested in various ways to confirm the predictions. We have a pretty good idea of what the olfactory receptors look like.

An example is shown in the figure on the left from a paper by Hall et al. (2004). This is the predicted structure of a mouse olfactory receptor that binds octanol. (Octanol is a sweet-smelling alcohol.) The bound molecule is shown as a red stick model in the side view (left) and the top view (right). The outside of the cell is at the top and that's where the odorant penetrates to the binding site.

The seven coils that you see in the structure are the seven α-helices that span the membrane. When the odorant binds, it changes the structure of the protein a little bit and this slight change includes the part of the receptor at the bottom, which is inside the cell. The change is enough to affect the binding of another protein, called a G-protein. This is what triggers the response.

Many different kinds of receptors activate a signalling pathway in the same manner as the olfactory receptors. A typical example is shown in the diagram below. In this case the signal is triggered by a hormone, but the same principle applies to signals triggered by odorants.


Look at the stimulatory pathway on the left. This is how the olfactory receptors work. When an odorant binds, the conformational change is transmitted through the receptor (R_s) to the inside surface of the membrane. G-protein (green) normally binds to the bottom surface of the receptor but when the receptor is triggered, G-protein is released and moves over to bind to another membrane protein called adenylate cyclase. The release and movement of G-protein is coupled to exchange of GDP for GTP. (GTP is a nucleotide like ATP. The proteins are called G-proteins because they bind GDP/GTP.)

Adenlyate cyclase is an enzyme that catalyzes the conversion of ATP to cyclic AMP (cAMP). cAMP in turn activates an enzyme called protein kinase A. Kinases are enzymes that attach phosphate groups to proteins. In this case, protein kinase A phosphorylates a protein within the neurons converting it from an inactive to an active form. Eventually the signal is transmitted to membrane pumps that are stimulated to alter the flow of charged ions into and out of the cell. This results in an action potential that passes up the axon to the brain.

This is a classic signal transduction pathway. The example shown in the figure is a simplified version with only a single protein kinase phosphorylation. In most cases there is a cascade of phosphorylations (and dephosphrylations) involving a number of different proteins. The study of signal transduction cascades is a major focus of hundreds of biochemistry labs.

The net result of all this biochemistry is that the presence of an odorant in your nose will eventually cause your brain to recognize it, as long as you have a receptor for that odorant. We have 388 different olfactory receptors so we can detect lots of different smells, including cat urine. Mice have 1037 different olfactory receptors so they can probably smell things that we can't. Maybe they can smell cats directly.

The olfactory receptor genes were discovered by Linda Buck and Richard Axel in 1991. They got the Nobel Prize in 2004 (see tomorrow's "Nobel Laureates").

The evolution of these genes in vertebrates raises some interesting questions about mechanisms of evolution. We'll learn about birth-and-death evolution later on this week.

Hall, S., Floriano, W.B., Vaidehi, N. and Goddard III, W.A. (2004) Predicted 3-D Structure for Mouse 17 and Rat 17 Olfactory Receptors and Comparison of Predicted Odor Recognition Profiles with Experiment. Chem. Senses 28: 595-616.

The Smell of Cat Pee

 
Most mammals have a keen sense of smell. That's why urinary odorants and pheromones are used to attract mates and mark territory. In most cases we can't detect these odors but there's one major exception.

The urine of cats contains chemicals that are easily detectable by humans. The smell is not pleasant. Mature cats will spay almost anything to stake out their territory, especially males). This isn't a problem if it's outdoors but it can be a major problem for indoor cats because carpets and spraying are not a good mix.

The urine of mature cats contains a chemical known as felinine (2-amino-7 -hydrozxy-5, 5-dimethyl-4-thiaheptanoic avid). Felinine excretion is stimulated by the hormone testosterone, which isn't produced until the cat reaches maturity. Both male and female cats excrete felinine in their urine but males typically excrete twice as much.

Felinine is odorless, to us. A recent paper (October 2006) describes how it is made and how it is converted to more pungent compounds.

The biochemical pathway leading to felinine begins with 3-methylbutanol- glutathionine (3-MBG) (compound A in the figure below). 3-MBG is a normal precursor in the synthesis of cholesterol but in cats some of it is converted to 3-methylbutanol-cysteinylglycine (3-MBCG) (compound B) by a pepdidase activity that removes glutamate. This reaction takes place in the bloodstream and 3-MBCG is excreted in the urine in cats of from the time they are born.

Mature cat urine contains high levels of protein, 90% of which is a medium-sized protein (70kDa) called cauxin. Cauxin levels rise as the cats reach maturity because transcription of the gene is stimulated by sex hormones. Cauxin is produced only in kidney cells and is secreted directly into the urine. The novel finding is that cauxin is a peptidase that cleaves 3-MBCG producing felinine (compound C). What this means is that production of felinine from 3-MBCG takes place in urine, probably in the nephrons before urine is released into the bladder.

Felinine breaks down into a number of smaller compounds that give rise to the characteristic smell of cat urine. The main breakdown product is 3-mercapto-3-methy-1-butanol formed by splitting felinine at the sulfur atom. Other breakdown products are formed. The complex mixture of derivatives is probably produced by a combination of unknown enzymatic act ivies and spontaneous reactions. The characteristic odor of domestic cats differs from that of lynx and bobcats and the differences are due to the concentrations of the various breakdown products of felinine.

Miyazaki, M., Yamashita, T., Suzuki, T., Saito, Y., Soeta, S., Taira, H., and Suzuki, A. (2006) A Major Urinary Protein of the Domestic Cat Regulates the Production of Felinine, a Putative Pheromone Precursor. Chemistry & Biology 10: 1071-1079.

Appeasers, Spaghetti Monsters, and NCSE

 
John West, one of the IDiots at the Discovery Institute, has posted an interesting article [Why Does National Center for Science Education (NCSE) Spokesman Think "Mocking Traditional Religion" is OK?].

West is referring to a newspaper article published in last Sunday's Toronto Star (see Church of the Flying Spaghetti Monster Makes Front Page of The Toronto Star). In that newspaper article, Glenn Branch of the National Center for Science Education (NCSE) defended the Church of the Flying Spaghetti Monster. West asks, why does NCSE think it's okay to mock religion in this case and yet go out of their way to defend religion in other cases?

We've heard for years from Branch's boss Eugenie Scott that evolution and religion are perfectly harmonious (indeed, the NCSE has helped use our tax dollars to promote the message that true theology endorses evolution, and its director Eugenie Scott has recommended that students study theological statements endorsing evolution during biology class). But now it turns out that mocking religion in the name of science is "probably healthy" and that it is illegitimate for proponents of ID even to question such anti-religious diatribes.

Good point. Does anyone know the answer? The people over at NCSE (and their allies like Ed Brayton) go apoplectic whenever some atheists criticize the silly superstitions of Ken Miller and Frances Collins. The Church of the Flying Spaghetti Monster mocks all superstitious beliefs, including those of theistic evolutionists. Why is one so bad but not the other?

As far as I'm concerned, it's just as much fun to mock theistic evolution directly as it is to do it through the Church of the Flying Spaghetti Monster.

Phases of the Moon

 
I've added the phases of the moon to the bottom of the left sidebar. This is in response to a request from somone who is really interested in astronomy and really interested in knowing whether my mood is affected by the phases of the moon. (It isn't, by the way. )

Some examples of the phases of the moon are shown below for viewing from Canada or Chile. Can you tell which is which? Do you know why they're different?

CURRENT MOON

lunar phases

CURRENT MOON

lunar phases

Compact Fluorescent Bulbs

 
Steve Reuland at Sunbeams from Cucumbers writes On the Wonders of Compact Fluorescent Bulbs. He makes a compelling case. I'm going to switch 10 light bulbs tonight.

Are Science Blogs Really About Science?

 
Greg Laden has posted a summary of the number of comments on articles put up on Pharyngula [Where's the beef(ing)?"]. As you might have guessed, there are way more comments on articles about creationism and religion than on articles about science.

This confirms my observation as well. I've also noted that straight reporting about, and praise for, the latest "breakthrough" seems to go down better than critical analysis and skepticism. In general, articles that challenge pre-conceived notions don't get as much attention as those that reinforce current dogma.

This raises the obvious question: are science blogs really about science?

Sometimes they are. Here's a list of the 50 best science posts as determined by an expert panel of judges [Science Blogging Anthology - The Council Has Spoken!]. Congratulations to the winners!

Why Are So Many Engineers and Physicians IDiots?

 
Stephen Meyer on Engineers and ID is an answer the the question of why are there so many engineers who believe in intelligent design, and why are there so few scientists. Meyer says it's because engineers are better able to recognize design. That's only part of the answer. The other, more important, part is that they don't know how to recognize good science because they're not scientists. They can't tell the difference between engineering and science.

The Cost of Mistakes address the observation that a higher percentage of doctors fall for ID compared to scientists. DaveScot explains that it's because doctors recognize the cost of mistakes. They know that an error will most likely have bad consequences so they see through the modern concept of evolution and recognize that errors can't lead to improvement. That's only part of the answer—and not a very important part. The real reason is that Doctors aren't scientists so they don't understand science even though they think they do because they passed biochemistry in medical school. That's why so many of them are IDiots.

Engineers and doctors play with science but they are not trained to be scientists. They are not biologists. They are not geneticists. They are not experts in evolution. It's about time we recognized that the vast majority of people who believe in intelligent design don't understand the first thing about science and how it's supposed to be done. That's why a higher proportion of non-scientists (doctors, lawyers, accountants, engineers, politicians) are IDiots.

If the Horse Is Dead, Why Keep Kicking It?

 
Bill Dembski notes the publication of two new book that demolish the arguments for intelligent design (Living with Darwin by Philip Kitcher and Darwin and Intelligent Design by Francisco Ayala). Dembski then asks If the horse is dead, why keep kicking it?.

I'm reminded of a quotation from a 1965 paper by Emil Zuckerkandl and Linus Pauling. They were publishing the first sequence based phylogenetic trees. When commenting on why we need more evidence for evolution they said ...

Some beating of dead horses may be ethical, where here and there they display unexpected twitches that look like life.

Zuckerkandl, E. and Pauling, L. (1965) in EVOLVING GENES AND PROTEINS, V. Bryson and H.J. Vogel eds. Academic Press, New York NY USA

Science Teaches Skepticism: That's a Good Thing

Monday's Molecule #8

 
Name this molecule. You must be specific. We need the exact chemical name and the common name. The chemical name isn't that hard but finding the common name and the function of the molecule is a lot more difficult. Comments will be blocked for 24 hours.

Comments are now open. Since I don't expect anyone to get the correct answer, I'll be posting the explanation in a separate article.

Most Important Medical Advance

 
Here's a poll that will make you think. The medical journal BMJ asks you to identify the single most important contribution to medicine since 1840 [Medical Milestones Poll].

It's a tough choice. I think I'll have to choose "sanitation."

[Hat Tip: Hsien Hsien Lei who wants you to vote for DNA.]