Thursday, August 28, 2008

The Plausbility of Life: Resolving Darwin's Dilemma

Michael White of Adaptive Complexity has written a multipart review of Kirschner and Gerhart’s The Plausbility of Life. White's posts are great reads and have made me want to buy the book. The general point made is that nature is a prolific recycler. Old tools are co-opted for new uses time and time again.

"It is much easier for an insect or vertebrate lineage to evolve new types of limbs, for example, than it is for a mollusc to evolve webbed feet. Why? Because insects and vertebrates already have the molecular toolkit for making limbs; to make a new type of limb (such as wings on a bat or dragonfly) requires only some tweaks to that tool kit - bats and insects did not have to evolve wings from scratch."

I find it appealing that molecular biologists are becoming increasingly interested in evolution, and that evolutionary biologists are becoming increasingly interested in molecular biology. The great schism in the field of biology during the 50's and 60's was certainly an artificial one, but seldom since have researchers ventured far beyond disciplinary lines.

Read Part 1, Part 2 and Part 3 here.

Saturday, August 23, 2008

This Week's Citation Classic: The Bible

No self-respecting molecular lab would be caught dead without Maniatis aka Sambrook and Russell aka The Bible aka Molecular Cloning: A Laboratory Manual.

First appearing in 1982, this laboratory standby was based on the protocols of the 1980 Molecular Cloning of Eukaryotic Genes course at Cold Spring Harbor Laboratory. The original lead author was Tom Maniatis, who picked up his skills in the Ptashne Lab and the Sanger Lab. Maniatis was hired by Harvard as a assistant professor in 1976, but fled to CSHL without even having stepped foot in his Harvard lab because of an ill-advised ban on research involving recombinant DNA by the Cambridge City Council. At CHSL, Maniatis produced the first full-length cDNA clone of a mammalian gene, b-globin.

Maniatis' coauthors for the 1st edition were Ed Fritsch and Joe Sambrook. Sales totalled 18,000 in the first year and eventually numbered 60,000, which is astounding of a technical manual.

The book is now in its 3rd and final edition (Sambrook and Russell eds.). Clocking in at $259, it is pricey but can be the best laboratory investment you will make, simply because, as George McCorkle wrote in American Scientist, “Mirabile dictu! The procedures in this manual nearly always work!” Another great strength is that the biology behind the protocols is carefully explained so one can troubleshoot any issues that arise.

Because the field of molecular biology changes so quickly, CHSL is changing to an online version of Molecular Cloning called CHSL Protocols. CHSL"realized that if [it was] going to continuously add new material, [CHSL] had to think of the project as a journal, and give it a full editorial staff. Moving things out from under the Molecular Cloning name also gave [CHSL] the freedom to expand [its] areas of coverage and bring in material from [its] other manuals, as well as publishing new original articles."

The web edition is nice and all, but I'm kind of a throwback because I prefer to have my TBE-stained copy on the bench besides me.

Photo: The Dennehy Lab reference shelf.

Thursday, August 21, 2008

New viral way of life discovered in deep-sea vents

Guy Plunkett of Enteropathogen Resource Integration Center pointed out this New Scientist article to me. I got a chuckle out of it.

The gist of the story is that Eric Wommack has discovered that many of the bacteria living near deep sea vents harbor viruses in their genomes. This is apparently a first for oceanic microbes.

New Scientist likes to play up discoveries like these. The article claims, "Marine phages - the viruses that parasitise bacteria and archaea in the sea - tend to infect their hosts, divide and burst them like balloons....Instead of hijacking bacteria to spawn offspring, these cell-splitting - or lysogenic - viruses insert their short genomes into the bacteria's own, endowing it with potentially useful genes." This is what the article claims is a "New viral way of life"!

Not hardly. Lysogeny is not exactly a new way of life. It was observed quite soon after bacteriophages were discovered in 1915-1917. Guiseppe Bertani (of LB broth) wrote a nice article about the early years. The quality of fact checking at New Scientist is apparently quite poor. Moreover the article cited by article does not in fact mention anything about lysogeny or deep sea vents for that matter. It is quite puzzling.

Tuesday, August 12, 2008

Book Review: Simplexity

Simplexity by Jeffrey Kluger promises to translate "newly evolving theory into a delightful theory of everything" which virtually guarantees failure. The "evolving new theory" is simplexity, a theory that posits complexity and simplicity are complementary. The "theory of everything" will apparently come later. It's not in this book.

Kluger's approach is to devote eleven chapters to questions such as "Why is the stock market so hard to predict?" and "Why do we worry about the wrong things?". But readers looking for something deeper than a light, fluffy discourse steeped in trivia will be disappointed. Each chapter is disjointed from the others, except for some vague hand-waving at how "complexity" is responsible for some puzzling behaviors.

This is not to say the book doesn't have its moments. Chapter 5 on "Why do people, mice and worlds die when they do?" is an interesting discussion of scaling problems and Klieber's mass to 3/4 power rule. Simplexity does entertain and is a great source of tableside trivia that should lead to some thought provoking conversations. However, readers looking for a solid introduction to complexity science should look elsewhere. I think this book is for people who want to read about "science" without actually reading Science. Other books in this shelf include "Blink" and "Freakonomics".

Monday, August 11, 2008

This Week's Citation Classic

This week's citation classic is relatively new, but has outsized importance, and should result in a future Nobel Prize for its primary author. The paper is Lee RC, Feinbaum RL and Ambros V. 1993. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75: 843-85.

Geraldine Seydoux once wrote about Ambros' discovery, "In 1990, Victor Ambros faced a conundrum. The search for the heterochronic gene lin-4 had led him to a 700-bp DNA fragment. This fragment could rescue a lin-4 mutant but contained no apparent open reading frame (ORF). The few small ORFs that could be detected were either not conserved in other nematodes or not essential for rescue. Two years and several RNAse protection experiments later, Victor Ambros was forced to conclude that the lin-4 gene product was not a protein at all, but a very small 20-base RNA—the first microRNA!"

Yeah so...

Yeah so Ambros et al. discovered an entirely new form of genetic regulation. At first, it was thought to be some "weird worm thing", a quirky aspect of the genetics of the roundworm C. elegans. That is, until Gary Ruvkun of Massachusetts General Hospital BLASTed another miRNA called Let-7. "Bingo" said Ruvkun, "up came the fly with a perfect match and the human [was another close match]. Within minutes I knew exactly what we were going to be doing for the next year." To date, 678 miRNA's have been discovered and it is believed that there are probably hundreds more.

Each miRNA can affect dozens or more mRNA's and alter gene expression with significant consequences for organismal function. "The miRNAs collectively have much of the genome under their influence," says Ambros. "They can affect almost any aspect of the biology of a cell or organism."

miRNA's and other small RNA molecules have made the science of gene regulation bewilderingly complex, but they also have opened up a window of opportunity for new types of therapies. To design an artificial miRNA or anti-miRNA, you need only know the sequence of the microRNA whose action you want to block or mimic. This may eventually lead to treatments for many diseases such as hepatitis C and cancer.

Figure: The secondary structure of a precursor microRNA sequence from Brassica oleracea, as predicted by MFOLD ( by M. Zuker. GIF generation by plt22gif, D. Stewart and M. Zuker 2007.

Thursday, August 7, 2008

Teaching Evolution

Here is a very nice site for teaching evolution from the University of California Museum of Paleontology. It is geared for K-12 science teachers and contains specific lesson plans for every grade level. Check out this comic explaining fitness.

Wednesday, August 6, 2008

PZ Wins the Internet

ERV found this article on google news and forwarded it to me. It is an interview with PZ Myers of Pharyngula by Jeff Gardner, CEO of PZ Myers recently caused quite a kerfluffle with his notorious "cracker" post.

According to the article, PZ's post is "No. 1 read and discussed blog post in the world."

That's pretty impressive for a developmental biologist from Morris, Minnesota.

Personally, I think the rhetoric, on both sides, is way too overheated, but I think this passage was pretty interesting.

Donohue and the Catholic League have sounded the alarm, and loudly, about Myers, especially concerning his antics with the Eucharist.

For his part, Donohue called Myers “part egotist, part bigot — his behavior is clearly designed to insult, hurt and intimidate Catholics.

“We want to know what the University of Minnesota [Morris] is going to do about professor Myers,” Donohue continued. “Clearly, the university would act in a situation in which someone was burning a cross to harass African-Americans or spray-painting swastikas to intimidate Jews. Why will they not act in this case?”

Good question.

I called the university and spoke with Daniel Wolter, director of the news service in the Office of University Relations.

In response to my questions, Wolter e-mailed me a prepared statement in which Jacqueline Johnson, chancellor at the university, said that the school had deactivated the link from the university’s website to Myers’ blog, but would not take any action against Myers because the university and Board of Regents “affirms the freedom of a faculty member to speak or write as a public citizen without institutional discipline or restraint.”

Are PZ's actions equivalent to racism? Does the "freedom of a faculty member to speak or write as a public citizen without institutional discipline or restraint" apply to racist and/or hate speech?

Photo: PZ in the snow from PZ's homepage.

Monday, August 4, 2008

This Week's Citation Classics: Host Induced Variation

Today epigenetics is all the rage, but it has its roots in a pair of papers appeared nearly simultaneously in 1952-1953.

Luria SE and Human ML. 1952. A nonhereditary, host-induced variation of bacterial viruses. J. Bact. 64: 557-569.

Bertani G and Weigle JJ. 1953. Host controlled variation in bacterial viruses. J. Bact. 65: 113-121.

Luria & Human and Bertani & Weigle independently discovered that bacterial hosts can affect the growth and phenotypic properties of their bacteriophages.

As Luria and Human put it, "In analyzing the relation between certain phages and certain mutants of their bacterial hosts, we have encountered a novel situation: the genotype of the host in which a virus reproduces affects the phenotype of the new virus. The phenotypic change suppresses the ability of the virus to reproduce in certain hosts but not in others....

Several B/4 mutants of Escherichia coli, strain B, when infected with phages T2 or T6, liberate these phages in a form designated as T*, which does not multiply in young cells of strain B or of its mutants. T* can multiply in a small proportion of old, starved cells of strain B, giving rise to a yield of the corresponding normal T phage."

This finding was quite puzzling at the time, especially since it appeared to subvert traditional Mendelian genetics. Later it was discovered that a number of different mechanisms were responsible for host-induced modification including DNA methylation, restriction modification, and glucosylation. Werner Arber, Daniel Nathans and Ham Smith eventually shared a Nobel prize for their discoveries relating to restriction modification.

When I was working in the Turner Lab at Yale, I noticed that some of my phages grew better on a novel strain when they were previously grown on native strain than when they were previously grown on a novel strain.
I found this phenomenon was kind of interesting and thought I might have been the first to discover this. I called it a "maternal effect". Naturally it was with considerable chagrin when I found out that Luria, Bertani, Weigle and Human had discoved this over 50 years before. On the other hand, I found it neat that I rediscoved something that those giants of microbiology had discovered. And I could console myself with the I was the first to find host-induced modification among RNA phages (maybe).

One more aspect of this discovery that deserves mention is that it highlights the congeniality of the phage group. Not only did each of these authors acknowledge the competing group in their citations, but Bertani and Luria even came up with a media recipe together. Today we call it LB broth.

Figure: Epigenetic Mechanisms Nature 441, 143-145 (11 May 2006)

Friday, August 1, 2008

New Webpage

I finally got around to making a webpage for my laboratory. Check it out!
I'd love feedback.