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Friday, November 12, 2010

First they laugh

I wrote about my first publication when it came out about a month ago. I might not have mentioned how difficult it was to get this story published. Prior to my arrival in the Spiegel lab, the other authors had worked diligently on the Sortase project for nearly two years. It had been submitted to several quality journals and roundly rejected by all of them for myriad reasons. Much to everyone's dismay, this story just seemed like it would never get published either because the journal editors didn't think the work significant or novel enough or because the editors found something to nitpick. The frustration in all of this was that we knew there was an important story to be told, and only if it would be taken somewhere, other people would agree.

This is a common scenario for many scientists. You've got exciting data to share, but the barriers to publication are very high. I'm not saying that's such a bad thing. Rigorous standards for publication are the quality control filter that makes the scientific literature more dependable than not. But when your work is solid and you've done what the reviewers want and you still can't get over that barrier, it's frustrating.

Well, we finally got over that bar with the publication of the Sortase paper. And our conviction about the significance of the work has been born out by the string of commentary the paper has gotten since its debut. The most significant of those just came out yesterday in Cell.

Redecorating the Walls

Antibiotic-resistant Staphylococcus aureus has emerged as a major public health threat, with the number of S. aureus-infection-related deaths on the rise. Nelson et al. (2010) present an innovative engineering approach to incorporate nonnative small molecules into the S. aureus cell wall—a technique that could have myriad implications for imaging bacteria, engineering organisms with novel functions, and, perhaps most importantly, discovering new therapeutics. To incorporate small molecules into the bacterial cell wall, small molecules conjugated to “cell wall sorting” peptides with the sequence LPETG were administered to S. aureus. These peptide sequences were recognized by the periplasmic enzyme sortase A, which covalently cleaves the peptide and attaches the new N terminus to lipid II in the cell wall. The authors confirm, using immunocryoelectron microscopy and mass spectrometry, respectively, that the peptides localize and covalently attach to the cell wall. Covalent attachment of small molecules then permits the incorporation of azido groups into the cell wall, which can undergo click reactions with alkyne groups in a manner that does not interfere with native cellular biochemistry. Thus, the authors demonstrate the ability to functionalize the bacterial surface with an array of reactive molecules, which could enable further perturbation and studies of bacterial process in vitro and in vivo.

J.W. Nelson et al. (2010). ACS Chemical Biology published online October 5, 2010. 10.1021/cb100195d.

Getting that kind of attention from a journal like Cell is confirmation that our work is valuable and adds to the field. Beyond that, I hope this attracts attention to the technology we developed and spurs further applications both by the Spiegel lab and others.

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