I've been struggling to get started, mainly because I couldn't identify an angle that reviewers would find persuasive. The more I learn about grant writing the more I realize how important it is to get the reviewer excited about your proposal; enthusiastic reviewers will overlook problems that bored reviewers would jump on. However a discussion today with the postdoc has suggested an angle that might work well - it's at least good enough to get going with.
Topic: In vivo role of the Haemophilus influenzae CRP-S regulon
Background: This regulon controls a wide range of phenotypes important for pathogenesis: biofilm formation, motility, DNA uptake, gene transfer, DNA replication...). It's active in vivo. We know a lot (but not enough) about its in vitro regulation. We've made and phenotyped knockouts of every gene.
Goals: Develop genetic tools for in vivo studies of the H. influenzae CRP-S regulon (e.g. control and inducible m-cherry fusions). Use in vitro and simulated-RT studies to characterize the effects of known respiratory tract conditions on regulon expression. In collaboration with an established animal-research lab (chinchilla ear or mouse lung model), carry out in vivo investigations of regulon expression and effects on pathogenesis.. one of the established animal models.
This angle builds very well on all our work under the previous grant (we're running on a no-cost extension so I guess it still counts as our current grant) and we can submit this proposal as a renewal rather than as a new grant.
One thing we'll need to do is identify a collaborator in whose lab the in vivo work can be done. Sending a senior grad student or postdoc to such a lab will be much more cost effective than setting up our own facilities.