Jörg Vogel Talks About Bacterial Pathogens
Fast Breaking Papers Commentary, February 2011
|
Article: The primary transcriptome of the major human pathogen Helicobacter pylori
Authors: Sharma, CM;Hoffmann, S;Darfeuille, F;Reignier,
J;Findeiss, S;Sittka, A;Chabas, S;Reiche, K;Hackermuller,
J;Reinhardt, R;Stadler, PF;Vogel, J |
Jörg Vogel talks with ScienceWatch.com and answers a few questions about this month's Fast Breaking Paper paper in the field of Microbiology.
Why do you think your paper is highly
cited?
Because it describes a generic approach to the analysis of organisms, including the full suite of cellular RNAs and precisely where they start. The paper also produced a reference data set for the large community of Helicobacter researchers.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
It describes a new methodology (cheap and easy global mapping of transcription start sites), new discoveries (of many small RNAs which had not at all been expected in Helicobacter), and the synthesis of knowledge (by comparison of our global data to results of work on individual transcripts or molecular complexes).
Would you summarize the significance of your paper
in layman's terms?
"I hope that our paper will remind funding agencies that work on bacterial pathogens is not only important in terms of human health, but also keeps answering fundamental aspects of life."
It makes the life of researchers working on the important pathogen, Helicobacter pylori, a lot easier. The same type of analysis can be repeated with any other bacterium (and already has been repeated with some), and will help other biologists to understand their favorite organisms much better.
How did you become involved in this research, and
how would you describe the particular challenges, setbacks, and
successes that you've encountered along the way?
A couple of things led me there. First, when we started this project in 2005, I wanted to challenge an emerging perception (or the rather unjustified assumption) that Helicobacter had no small RNAs. I was convinced that all bacteria use small RNAs as regulators of gene expression, you just would need to look for them in the right way.
Second, we were also looking for small RNAs in Helicobacter because we were interested in a protein called Hfq, which binds small RNAs in E. coli. However, Helicobacter, like 50% of all bacteria, did not seem to have a direct homolog of E. coli Hfq. We reasoned that if we find small RNAs, we could use them as baits to discover an alternative small RNA-binding protein that might then be present in these many other Hfq-less species as well.
The biggest challenge was that we started using 454 sequencing very early, when it was still very expensive and hardly available. We lost many months waiting for sequencing results, and I remember how my hand trembled when I had to sign the bill of 20,000 Euro for our first sequencing run before we even knew how well our approach would work. That just happened to be almost half of my annual research budget at the time. But you just need to make an investment when you think you are on the right track.
The biggest successes, I would say, was that when we submitted our data for publication, the reviewers were genuinely positive and constructive, and that there was quite some enthusiasm in the community even though it was our first-ever paper on Helicobacter. I have also been told that our paper was one of very few that got rated by both Faculty1000 Biology and Medicine. I felt that this was quite rewarding in the light of the fact that, despite building fierce competition on RNA sequencing approaches, we had kept working to improve the data analysis until we felt that this could be a lasting contribution to the field.
Where do you see your research leading in the
future?
We have in the meantime mapped, in collaborations, the primary transcriptomes of many diverse species ranging from archaea to cyanobacteria, and I assume that given the drop in sequencing costs, similar maps will be generated for almost all bacteria microbiologists are possible interested in. Our own research is now focused on bringing RNA sequencing to the level of a single bacterial cell.
Do you foresee any social or political
implications for your research?
Well, I hope that our paper will remind funding agencies that work on
bacterial pathogens is not only important in terms of human health, but
also keeps answering fundamental aspects of life.
Jörg Vogel
Professor and Chair
Institute of Molecular Infection Biology
University of Würzburg
Würzburg, Germany
KEYWORDS: HELICOBACTER PYLORI, TRANSCRIPTOME, GENOME SEQUENCE, NONCODING RNA OUTPUT, dRNA-seq, GENOME-WIDE MAP, TRANSCRITIONAL START SITES, OPERONS, POLYCISTRONS, ANTISENSE TRANSCRIPTION, MESSENGER RNA, RNA-POLYMERASE, ESCHERICHIA COLI, GENE EXPRESSION, COMPARATIVE GENOMICS, 6S RNA, IDENTIFICATION, PROMOTER, SEQUENCE, BACTERIA.