If I had known of this in August!

The title of a recent paper that is available at the Genome Research web site:  “Windshield splatter analysis with the Galaxy metagenomic pipeline”

I could have provided a kilogram or more of sample from my recent move-in trip.

The abstract of this paper:

How many species inhabit our immediate surroundings? A straightforward collection technique suitable for answering this question is known to anyone who has ever driven a car at highway speeds. The windshield of a moving vehicle is subjected to numerous insect strikes and can be used as a collection device for representative sampling. Unfortunately the analysis of biological material collected in that manner, as with most metagenomic studies, proves to be rather demanding due to the large number of required tools and considerable computational infrastructure. In this study, we use organic matter collected by a moving vehicle to design and test a comprehensive pipeline for phylogenetic profiling of metagenomic samples that includes all steps from processing and quality control of data generated by next-generation sequencing technologies to statistical analyses and data visualization. To the best of our knowledge, this is also the first publication that features a live online supplement providing access to exact analyses and workflows used in the article.

The citation:

Kosakovsky Pond S, Wadhawan S, Chiaromonte F, Ananda G, Chung WY, Taylor J, Nekrutenko A; The Galaxy Team. Windshield splatter analysis with the Galaxy metagenomic pipeline.  Genome Res., Published in Advance October 9, 2009, doi: 10.1101/gr.094508.109.

It’s all about ribosomes

What is all about ribosomes?  Undoubtedly, readers will quickly make the connection between the title of this short essay and the recent awarding of the 2009 Nobel Prize in Chemistry to three whose work has centered on the ribosome.  The Nobel prize announcement emphasized the links between ribosomes and antibiotics, rightly focusing attention on the fact that many antibiotics target the bacterial ribosome, different as it is from its eukaryotic (cytosolic) counterpart in important ways.  What I want to do is to ramble on about some other aspects of ribosomes that I find fascinating.  Hopefully, by turning some features of biology on their heads, readers will think differently about genomes, gene expression, and other facets of molecular biology.

The Nobel Prize in Chemistry 2009

It’s a great week for RNA biology.  Early today, it was announced that the 2009 Nobel Prize in Chemistry was awarded to Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada E. Yonath for their work on the structure and function of ribosomes.  For the uninitiated, the ribosome is the central feature of life (moreso than even DNA!), and it is at its core a ribozyme.

As was stated in the abstract of a recent review by Steitz:

The ribosome is a large ribonucleoprotein particle that translates genetic information encoded in mRNA into specific proteins. Its highly conserved active site, the peptidyl-transferase center (PTC), is located on the large (50S) ribosomal subunit and is comprised solely of rRNA, which makes the ribosome the only natural ribozyme with polymerase activity.

From the press release:

This year’s Nobel Prize in Chemistry awards Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath for having showed what the ribosome looks like and how it functions at the atomic level. All three have used a method called X-ray crystallography to map the position for each and every one of the hundreds of thousands of atoms that make up the ribosome.

….

An understanding of the ribosome’s innermost workings is important for a scientific understanding of life. This knowledge can be put to a practical and immediate use; many of today’s antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive. This is why ribosomes are such an important target for new antibiotics.

This year’s three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity’s suffering.

What a great subject – from the RNA World (at the very dawn of life!) to modern medical microbiology.

The Nobel Prize in Physiology or Medicine 2009

The announcement is here.  The award goes to Elizabeth Blackburn, Carol Greider, and Jack Szostak “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase”.  Needless to say, RNA is woven intricately into this subject.

Intron-mediated enhancement of gene expression

Most genes in eukaryotes (well, at least eukaryotes that are not Saccharomyces cerevisiae) possess introns, sequences that are transcribed by RNA polymerase II and subsequently spliced out from the primary transcript.  Introns have been the subject of tremendous interest since their discovery in the 1970’s, and have provided much insight (and grist for controversy) into subjects as disparate as junk DNA, the RNA World, and mechanisms of gene expression.  Among the still-unresolved matters today has to do with the timing of splicing – is it cotranscriptional* or does it occur after polII has released the transcript.

The case for co-transcriptional splicing has been built in part through numerous studies that reveal physical connections between splicing factors and the transcriptional complex; many (most) of these involve the so-called CTD (C-Terminal Domain) of RNA polymerase II.  (This recent review summarizes this emerging field.)  The general idea is that, owing to the association of splicing factors with the CTD of polII, they are able to bind the nascent transcript and initiate splicing before polII has completed the synthesis of the primary transcript.