Starting out: Early Research Program Development and Leveraging the RDFP (a personal reflection)

1. Starting out: Early Research Program Development and Leveraging the RDFP (a personal reflection) Richard A. Wilson Plant Pathology rwilson10@unl.edu

2. Rice Blast Disease: Magnaporthe oryzae Panicles: Neck blast Leaves: Necrotic lesions Seeds Losses/year: 10-30 % 60 million people = $6.6 billion

3. Potato blight Wheat stem rust Back sigatoka Witch weed Asian soybean rust Cassava brown streak virus Science, 2/2010 Vol. 327

5. Tps1 controls metabolic functions and fungal virulence through mediation of NADPH/NADP levels Wilson et al.,2010. PNAS. NIA1encoding nitrate reductase GTR1encoding glutathione reductase GRT1

6. Tps1 controls metabolic functions and fungal virulence through mediation of NADPH/NADP levels Wilson et al.,2010. PNAS. NIA1encoding nitrate reductase GTR1encoding glutathione reductase GRT1 Pathogenic gene discovery in the rice blast fungus-USDA and NSF (IOS)

7. Tps1 controls metabolic functions and fungal virulence through mediation of NADPH/NADP levels Wilson et al.,2010. PNAS. NIA1encoding nitrate reductase GTR1encoding glutathione reductase GRT1 Pathogenic gene discovery in the rice blast fungus-USDA and NSF (IOS) Exploring a new role for NADPH in cellular signalling- NIH (EUREKA, R01) and NSF (Networks and Regulation)

8. The value of RDFP: • Condensation of ideas • I think this is key. It disciplines us to think in terms of asking very simple questions and focuses our research: • How does Magnaporthe cause disease? • Is NADPH a new signaling molecule? • In my field the difference between successful scientists who are platform speakers and those who are not is that the former have simple questions. This is reflected in their grantsmanship.

9. The value of RDFP: • 2) Leverage support for preliminary data: NSF EPSCoR First Award, other internal awards. • If you are invited to submit a full proposal to EPSCoR, use it to fund preliminary data or address likely concerns of the reviewers. • (eg new techniques)

10. RDFP is crucial for the clear presentation of ideas that is lacking in proposals from non-RDFP colleagues

11. Wilson, NSF

12. How have my RDFP-inspired proposals been received? Wilson et al.,2010. PNAS. NIA1encoding nitrate reductase GTR1encoding glutathione reductase GRT1 Pathogenic gene discovery in the rice blast fungus-USDA and NSF (IOS) Exploring a new role for NADPH in cellular signalling- NIH (EUREKA, R01) and NSF (Networks and Regulation)

13. Comments: Strengths: “The PIs studies on Tps1 suggest a new paradigm for how these trehalose-6-phosphatases may regulate biological processes.” 

”M. oryzae is amenable to the genetic approaches that the PI plans to utilize. The PI who has worked with filamentous fungi for the last decade, has the necessary expertise, genetic tools and resources to conduct these studies.” 

”The PI has clearly thought about pitfalls for each objective and provided alternative approaches.”

14. “The proposal has several strong points with a novel and interesting hypothesis that has the potential to result in a paradigm shift in our understanding of metabolic regulation by NADPH.” “The educational outreach component is among the best I have ever read for a standard NSF proposal.” “In total, this is a very good proposal, worthy of NSF support.” “Overall, very exciting work.” “In my opinion the intellectual merit of the research objectives is high.”

15. So, the objectives are clearly understood, the proposal is considered well written, the hypotheses are exciting. The proposals are not failing because of their intellectual merit or broader impacts, so why are they not getting funded?

16. Weaknesses: “This project is overly ambitious for the personnel. This is the single weakness in an otherwise flawless proposal.” “The project is too ambitious.” “There was some concern that the proposal was over-ambitious and that the proposal would be strengthened by improving the focus, perhaps by deleting aim 3.” “This is a very ambitious project.”

17. What to do? 1) Publish and go to meetings, create a buzz: (Papers for Plos Genetics, EMBO, Plos Pathogens, Mol Micro and Current Biology are in various stages of completion)

18. What to do? Submit a number of proposals.This is my strategy and its effectiveness is backed up by a study last week in Nature : “The best way to get grant proposals funded once success rates fall to around 15% is to bombard the market with applications, a mathematical analysis suggests....One group produced one proposal a year, and if funding was gained, ceased submissions until the last year of its grant. The other group produced one proposal every six months irrespective of whether a grant was awarded” When success rates edge down, "inefficiencies in the system take over", explains Roebber. "The only way to counteract them is by putting in more and more proposals."

19. What to do? 3) Meet your program managers/ talk to panel members: Quotes from panel members cornered at international meetings I spoke at (off the record): “...you’ve heard the expression third time lucky..”-NSF panel member “...new investigators are back of the line...”-NSF panel member “...NIH are funding no new investigators (?!)..”-NIH panel member “....panel members look for any excuse to reject a proposal..” NIH, NSF and USDA. “....success rates for the AFRI foundation grants (USDA) will be 5 %..”-USDA panel manager (although meeting her in person has allowed me to lobby for my lab, and she is very supportive of the work we do). “... that’s a definite CAREER proposal...” NSF BIO director.

20. Final thoughts: Getting grants is tough but not impossible. If you do have to “wait your turn”, RDFP training puts you ahead of the pack and positions you favorably for the grants you deserve.