Grant proposal plans (yes, again...)

But this time it's not just plans for a proposal to CIHR (the Canadian equivalent of NIH).  I'm certainly also going to apply to NSERC (the Canadian equivalent of NSF) and maybe to other agencies too (Cystic fibrosis?  NIH?).

NSERC grants are much smaller than CIHR grants, but they have one big advantage - that they're not restricted to health research.  For me this is important, as it will let me write a proposal that spells out the biggest reason I think my research is important, which has no health implications.

I'm having several colleagues read the previous (unsuccessful) proposal, asking specifically for big-picture feedback on whatever fundamental problems it might have.  I've had feedback from two, and they both say that the arguments for significance are weak.  Unfortunately the significance that drives me is pure research, not health-related, and I downplay this in the proposal because I know from experience that the reviewers won't appreciate it.  I clearly need to clarify and better-communicate the health-related reasons our work is important.

So I'm going to start here by simply tabulating all the significances I can come up with, health-related and not.

1. DNA uptake leads to transfer of antibiotic resistance genes into previously sensitive strains.
2. DNA uptake leads to changes in the cell surface that create strains insensitive to current vaccines.
3. If uptake specificity exists for mechanistic reasons (not mate-choice) then bacteria don't have any analog of eukaryotic sex (no mechanisms evolved because of selection for creating new combinations of genes or alleles).
4. Bacteria may use binding to extracellular DNA as a way to adhere to mucosal surfaces and biofilms.
5. In the human body DNA is a valuable nutrient source that promotes bacterial persistence and virulence.
6. DNA uptake is a novel kind of transport problem with special challenges (very long stiff charged molecules) - understanding how it's done will shed light on other membrane-transport problems.
7. The H. influenzae T4P DNA uptake system (and that of other Pasteurellaceae) is unique in lacking any obvious retraction motor protein. 
8. Type IV pili are important virulence determinants, especially for adhesion (but H. influenzae doesn't appear to normally have pili).
9. H. influenzae is a major human pathogen in all vulnerable populations.
10. H. influenzae is the model system for studies of competence in the gamma-proteobacteria.
11. Understanding DNA uptake will shed light on the physical properties of DNA.
12. Understanding DNA uptake specificity will shed light on the physical properties of DNA.
13. Antibiotics (some) induce competence in some/many species

These are all fine significances, but they have problems.  Either they're not a high priority for the review committee (e.g. the Microbiology and Infectious Diseases committee really doesn't care about evolutionary issues, transport problems, or the physical structure of DNA), or it's not easy to use them to make a strong case for the experiments we've been proposing (e.g. we're not addressing the consequences of DNA uptake).