Monday, April 30, 2007

What has phage lambda ever done for us?

Murray and Gann published an essay in this month's Current Biology titled "What has phage lambda ever done for us?" Since my current study organism is phage lambda, naturally I was interested. The essay is informative and interesting and, for those who have institutional access, I urge you take a gander at it for your own edification.

Bacteriophage lambda was first discovered in 1951 by Esther Lederberg (wife of Nobelist Joshua Lederberg and probably deserving of a Nobel in her own right, but that's another story). Lambda was immediately interesting to the burgeoning molecular biology community because it propagates by two alternative pathways: lytic and lysogenic. In the lytic cycle, the phage's DNA enters an E. coli cell, induces the cell to produce phage progeny, then subsequently causes the cell to lyse (break open) releasing the contents into the surrounding media. By contrast, the lysogenic cycle is largely harmless, possibly even beneficial, to the cell. Here the phage's DNA enters the cell whereupon it is integrated into the cell's own DNA. As the cell replicates, the phage replicates as well. How cool is that?

Murray and Gann highlight where phage lambda was used as a model organism in many major biological discoveries. Here is a ^not so^ brief listing:

* gene regulation (Lwoff, Jacob and Monod 1961; Roberts 1969; Guarneros and Galindo 1979)

* DNA recognition and cooperative binding (Ptashne 1967)

* genetic fine structure (Benzer 1957)

* messenger RNA (Volkin and Astrachan 1956, 1957)

* acquisition and loss of genes from genomes (Campbell 1959, 1962)

* triplet nature of DNA code (Crick, Barnett, Brenner and Watts-Tobin 1961)

* restriction and modification (Dussoix and Arber 1962)

* DNA and protein are colinear (Sarabhai, Stretton, Brenner and Bolle 1964)

* DNA ligase (Gellert 1967)

* epigenetic gene regulation (Ptashne 2004)

* chaperones and protein folding (Georgeopoulos, Hendrix, Casjens and Kaiser 1973)

* repression and activation (i.e. turning genes on and off, Ptashne 2004)

* molecular basis of DNA recombination (Meselson and Weigle 1959, 1961)

That's quite a list. And it is nowhere near being exhaustive. Phage lambda has proven uniquely malleable in the laboratory and has illuminated large facets of previously hidden knowledge to biologists. Today lambda is still being used in many laboratories, which is testament to its enduring legacy.

The photo depicts Ur-Lambda (the father of all laboratory lambda phages); it's a lambda with LEGS! *ahem* tail fibers. The Electron Microscopy image was taken by Bob Duda at the Pittsburgh Bacteriophage Institute.


  1. I had a large section on the genetic switch in my textbook back in 1993 (the chapter on Regulation of Gene Expression). It wasn't popular. Most teachers objected. They thought bacteriophage weren't relevant to mammalian gene expression—as if that's the only thing students need to know.

    At one point my colleagues and I outlined an entire basic molecular biology courses that used only lambda to illustrate all the basic principles. While this may seem a touch biased, it's quite doable. That's sad.

    Today's students have no idea of the importance of the 'phage group and their important contributions.

    BTW, T4 is better! :-)

  2. I was lucky to have a Intro to Genetics teacher who emphasized the history of genetics in her instruction. That history was largely consisting of bacteriophage history.

    I'd love to see your outline of a molecular biology course using just lambda!

    Oh and don't even get me started about the supposed lack of relevancy of phage to mammalian systems. When Journal of Virology doesn't publish phage papers, something must be wrong!

  3. Just to pick a few nits -- the phage involved in these classic studies was NOT lambda. It was T4.

    * genetic fine structure (Benzer 1957)
    * triplet nature of DNA code (Crick, Barnett, Brenner and Watts-Tobin 1961)
    * DNA and protein are colinear (Sarabhai, Stretton, Brenner and Bolle 1964)

  4. Actually the studies mentioned do feature the phage lambda as well as T4.

    In Benzer 1955 (I mistakenly cited 1957), Crick et al. 1961 and Sarabhai et al. 1964, lambda is used as a selective agent to reveal mutated strains. Wild-type phage are able to grow on both E. coli B and E. coli K12 (E. coli CR63, a su+ streptomycin-sensitive K12 strain was used in Sarabhai et al. 1964). However, strains mutated in the rII regions were unable to grow on K12 because K12 contains the lambda prophage.

  5. A quite recently emerging technique developed by the labs of Francis Stewart and Neil Copeland (ET cloning or recombineering) that allows cloning without restriction sites is based on lambda proteins gam, bet and exo. Thus, it is still worthwhile to study lambda today.

  6. Don Court's lab is primarily responsible for developing recombineering using the phage lambda Red system. The RecET genes used by Frances Stewart are from the Rac prophage.