The new CRP/CRP-S manuscript

Now that we’ve resubmitted both the USS manuscript and the Sxy manuscript, we’re starting to fix up yet another manuscript, this one about the interactions between CRP and its recognition sites in H. influenzae and E. coli. This manuscript was reviewed by a high quality journal last spring and politely rejected. The reviewers thought that our research was fine, but the results were not considered important enough to meet this journal’s standards,

I hadn’t looked at the manuscript since we submitted it in May, and had forgotten much of what it said, so I was able to reread it now with an open mind. I found lots of places where we could have done a better job of explaining the significance of what we were reporting. I then went over the manuscript with the post-doc who had done the work and most of the writing (as part of his PhD research). He has designed several nice additional experiments, and we had to decide which of these were worth doing before submitting the manuscript to another journal. In going over these and my rewriting ideas we saw that the manuscript could become much more strongly focused. So now we’re quite enthusiastic about what we (well, I) originally saw as a rather inconclusive little paper.

It’s too bad we weren’t able to make these improvements before submitting it the first time – the reviewers might then have found it acceptable. But I’ve had the same experience several times before: A manuscript we think very important is rejected by a very competitive journal. We polish it and submit it to another competitive journal. It’s again rejected so we polish it some more, and add in the new data or analyses that have accumulated since the first submission. It’s now accepted by a less prestigious journal, but is so much better that we think it would have been acceptable to the first journal we tried. If only....

Where was I?

A brief (I hope) loss of focus.... Now what were the main things I'm working on?

The CRP-S manuscript and the USS-2006 manuscript have both been officially accepted and proof-read. All that's left to do is pay the enormous open-access publication charges. As soon as we have the final formatted PDFs I'll replace the manuscript pdfs in the sidebar.

The sxy manuscript: Analysis of 5 hypercompetent mutants, effect of compensatory mutations, structure predicted by Mfold and confirmed by RNase mapping, effects on transcription and translation measured by lacZ fusions, real-time PCR and protein immunoblots. These experiments are all done, but the manuscript writing has stalled.

The USS-definition analysis/experiments/manuscript: 1. Characterization of genomic USS ("USS-G") by Gibbs motif searching, including effect of direction of DNA replication and of protein coding (and maybe reading frame): These experiments are partly done. 2. Re-analysis of published sequences of DNA fragments that are preferentially taken up: This is mostly not done yet. 3. Uptake experiments using DNA fragments with specific differences in USS sequence: This is mostly done. 4. Writing the manuscript: This morning the post-doc and I will sit down together to reconcile the three different versions of the Introduction. Some of it we'll move to the Discussion. The Results section is mostly not written yet - starting this will clarify what results still need to be generated. Much of the Methods is already written.

The Perl simulation: The post-doc is away for a week, leaving a simulation running on Stingray, our fast new Mac (all our computers are named for Australian animals). It's still not at equilibrium after almost a week, and the simulated sequence has accumulated a lot of USSs. The plan is to explore a range of parameter values (mutation rate, uptake bias) and then introduce some more complications (hmmm, what were they???).

The grant proposal: Create an 11-page compelling description of our past and future research. Still a long way to go, especially on the "compelling" part.