1. “Under Construction” Building the Best Possible (Team) Grant Proposal

2. Components of a Successful Grant Good ideas Good ideas Good writing Good writing Well thought-through hypotheses, outcomes, contingencies Well thought-through hypotheses, outcomes, contingencies Clear sense of “team science” Clear sense of “team science”

3. Specific to MBP 1018: Components of the Team Science Grant Abstract (1 page) Abstract (1 page) Rationale (0.5 page) Rationale (0.5 page) Background and preliminary data (2.5 – 3.5 pages) Background and preliminary data (2.5 – 3.5 pages) Overall objective and hypothesis (0.5 page) Overall objective and hypothesis (0.5 page) Outline of specific aims and team collaborations (0.5 page) Outline of specific aims and team collaborations (0.5 page) Detailed description of team members’ specific aims (4 pages per person) Detailed description of team members’ specific aims (4 pages per person) –Objectives, hypotheses, study designs, contingencies, outcomes Summary and future directions (1 page) Summary and future directions (1 page) –Includes integration of the work of team members Translational significance (0.5 page) Translational significance (0.5 page) Feasibility and timeline (0.5 page) Feasibility and timeline (0.5 page) References References

4. Introduction/Background Review the RELEVANT literature Review the RELEVANT literature This is not meant to be an exhaustive literature review, but rather a discussion of what is most important to what you want to do This is not meant to be an exhaustive literature review, but rather a discussion of what is most important to what you want to do Provide background for the disease and questions you will be addressing Provide background for the disease and questions you will be addressing Also provide background about any novel technical approaches Also provide background about any novel technical approaches Include a succinct rationale for the project (concept and approach) Include a succinct rationale for the project (concept and approach)

5. Specific Aims Should address: Should address: –What are the major questions your project is designed to address? –What are the objectives of your project? –How will each objective address the project-specific questions?

6. Hypotheses VERY IMPORTANT TO INCLUDE THESE!! VERY IMPORTANT TO INCLUDE THESE!! Each hypothesis should correlate, where possible, with a specific objective or question being addressed Each hypothesis should correlate, where possible, with a specific objective or question being addressed EXCEPT when you are addressing a technical objective (e.g., the creation of an experimental system) EXCEPT when you are addressing a technical objective (e.g., the creation of an experimental system)

7. Methodology Describe your experiments in detail Describe your experiments in detail Focus on study design Focus on study design –Study design should match up with objective Reference previously established techniques, except for specific modifications Reference previously established techniques, except for specific modifications –For example, no need to describe RNA isolation in detail…unless that’s your project! Need to address where your samples are coming from Need to address where your samples are coming from

8. Probable Outcomes/Contingencies What do you expect to observe? What do you expect to observe? What are your plans in case your experimental system goes awry? What are your plans in case your experimental system goes awry? You should not merely describe your experimental plan – the reader would not be expected to know how the studies are supposed to turn out You should not merely describe your experimental plan – the reader would not be expected to know how the studies are supposed to turn out Under what circumstances will your hypothesis be: Under what circumstances will your hypothesis be: –Proved? –Disproved? What will you do if something doesn’t work out that the rest of the project is dependent upon? What will you do if something doesn’t work out that the rest of the project is dependent upon?

9. Translational Application How is your project relevant to the human condition, and to patients? How is your project relevant to the human condition, and to patients? Describe the relevance and importance of your work to the diagnosis, prevention and treatment of cancer or the appropriate disease Describe the relevance and importance of your work to the diagnosis, prevention and treatment of cancer or the appropriate disease Be careful – sometimes use of patient samples is not sufficient for translational application! Be careful – sometimes use of patient samples is not sufficient for translational application!

10. Feasibility of Studies Most grants are funded for a 2-5 year timeframe Most grants are funded for a 2-5 year timeframe You need to ensure that, whatever you propose, it can be accomplished within that window You need to ensure that, whatever you propose, it can be accomplished within that window –Aim for 3 years, knowing that you have margin for error in that regard Be careful about # samples and types of experiments you propose Be careful about # samples and types of experiments you propose –For e.g., a microarray study on a cohort of 100 patients, prospectively over time (collecting 5 samples total) amounts to 500 array experiments, plus controls! –For Affymetrix GeneChip expression arrays, that’s easily $300K

11. Referencing Be consistent in terms of style Be consistent in terms of style # references provided are often an indicator of effort put into proposal development # references provided are often an indicator of effort put into proposal development At a graduate level, anything less than 20 references is NOT acceptable At a graduate level, anything less than 20 references is NOT acceptable

12. Evaluation: Is this team science? Abstract (1 page) Abstract (1 page) Rationale (0.5 page) Rationale (0.5 page) Background and preliminary data (2.5 – 3.5 pages) Background and preliminary data (2.5 – 3.5 pages) Overall objective and hypothesis (0.5 page) Overall objective and hypothesis (0.5 page) Outline of specific aims and team collaborations (0.5 page) Outline of specific aims and team collaborations (0.5 page) Detailed description of team members’ specific aims (4 pages per person) Detailed description of team members’ specific aims (4 pages per person) –Objectives, hypotheses, study designs, contingencies, outcomes Summary and future directions (1 page) Summary and future directions (1 page) –Includes integration of the work of team members Translational significance (0.5 page) Translational significance (0.5 page) Feasibility and timeline (0.5 page) Feasibility and timeline (0.5 page) References References

13. Complete this chart for yourselves… Member 1 Member 2 Member 3 Member 4 Month 1-6 Month 7- 12 Month 13- 18 Month 19- 24 Month 25- 30 Month 31- 36

14. Each group should… Know the points of collaboration Know the points of collaboration Know how all the projects “fit” together (what does the puzzle look like?) Know how all the projects “fit” together (what does the puzzle look like?) Know the team’s failure modes Know the team’s failure modes Know each other’s timelines Know each other’s timelines

15. Evaluation: Is the project planning strong? Abstract (1 page) Abstract (1 page) Rationale (0.5 page) Rationale (0.5 page) Background and preliminary data (2.5 – 3.5 pages) Background and preliminary data (2.5 – 3.5 pages) Overall objective and hypothesis (0.5 page) Overall objective and hypothesis (0.5 page) Outline of specific aims and team collaborations (0.5 page) Outline of specific aims and team collaborations (0.5 page) Detailed description of team members’ specific aims (4 pages per person) Detailed description of team members’ specific aims (4 pages per person) –Objectives, hypotheses, study designs, contingencies, outcomes Summary and future directions (1 page) Summary and future directions (1 page) –Includes integration of the work of team members Translational significance (0.5 page) Translational significance (0.5 page) Feasibility and timeline (0.5 page) Feasibility and timeline (0.5 page) References References

16. Building a Specific Aim Aim title “To determine”/”Determining” X in Y - Use strong action verbs where possible - Don’t hand wave or write “diffidently” Rationale “Given that [X, Y and Z], it is likely that [A, B and C] are true” - Set up as a series of logic statements - It’s OK to recap some preliminary data or language from the rationale (expected, even) - Can be combined with your hypothesis statement (see below), but doesn’t have to be – and in some cases, probably shouldn’t be Hypothesis “We therefore hypothesize X” - Make sure it’s falsifiable! Study design “In order to test this hypothesis, we will use samples derived from [X and Y] in order to conduct experiments [1, 2, 3 and 4]” - Don’t go overboard with methods – unless it’s not something the reviewer is expected to be familiar with - Outline where your sample tissues are coming from - Give enough detail so that the reviewer knows what you intend to do - For discovery grants: Give specifics of data analysis methodology here

17. Building a Specific Aim Anticipated Outcome “If [X] is observed…” - Be CONCISE yet SPECIFIC - Don’t do more than one outcome at a time, as a rule – otherwise, it makes it hard to follow what’s going on. Interpretation “…then [Y] must be true” - Directly linked to your anticipated outcome - Your chance to explain what you think your outcomes mean and how they support/refute your hypotheses Contingency “However, if A is observed, then we will do B” - Your chance to say “OK, I know things can go wrong – here’s why this isn’t a lost cause!” - Contingencies can be necessary for technical reasons as well as for scientific ones - Repeat outcome/interpretation/contingency IF/THEN statements as often as necessary Summary and significance “Therefore, taken together, these studies will allow us to determine [X]” - Feel free to restate your aim language - Pull it all together – what does this aim mean, taken as a whole?

18. Caveats Mahadeo’s favourite way to write aims Mahadeo’s favourite way to write aims NOT the only approach NOT the only approach –Personal idiosyncrasies in style –Clinical aims usually don’t fit the model –Discovery aims can fit the model, with some creativity

19. Evaluation: Is this translationally relevant/significant? Abstract (1 page) Abstract (1 page) Rationale (0.5 page) Rationale (0.5 page) Background and preliminary data (2.5 – 3.5 pages) Background and preliminary data (2.5 – 3.5 pages) Overall objective and hypothesis (0.5 page) Overall objective and hypothesis (0.5 page) Outline of specific aims and team collaborations (0.5 page) Outline of specific aims and team collaborations (0.5 page) Detailed description of team members’ specific aims (4 pages per person) Detailed description of team members’ specific aims (4 pages per person) –Objectives, hypotheses, study designs, contingencies, outcomes Summary and future directions (1 page) Summary and future directions (1 page) –Includes integration of the work of team members Translational significance (0.5 page) Translational significance (0.5 page) Feasibility and timeline (0.5 page) Feasibility and timeline (0.5 page) References References

20. Evaluation: Is the writing solid? Tips for success Tips for success –Follow formatting guidelines –Make the grant look “pretty” –Proofread!!! –Catch silly mistakes (e.g., “Western blots detect DNA”) –Team science = team reviewing and editing

21. Evaluation: Is the writing solid? What does a reviewer look for? What does a reviewer look for? –Flow –Grammar and spelling –A “team voice” in writing – no jarring discontinuities between sections –Glaring errors and inconsistencies –“Mosquitoes” – irritants to the reviewer that are idiosyncratic of their own reading/writing style

22. How to use Figures/Tables Show off somebody else’s preliminary data Show off somebody else’s preliminary data Schematics of models Schematics of models Workflows (especially for data analysis methods) Workflows (especially for data analysis methods) Timelines Timelines “Concept maps” “Concept maps”

23. Clarity Grant should be written as if it were directed at a general scientific audience Grant should be written as if it were directed at a general scientific audience You are the most knowledgeable person with respect to what you have written You are the most knowledgeable person with respect to what you have written Do NOT make assumptions about what the reviewer knows or not Do NOT make assumptions about what the reviewer knows or not Be CLEAR Be CLEAR EXPLAIN yourself EXPLAIN yourself Your work should be able to be intuitively followed by the reviewer Your work should be able to be intuitively followed by the reviewer

24. What to Make Sure You Do When Writing A Grant Follow formatting guidelines carefully Follow formatting guidelines carefully –10 double spaced pages –Page count does not include figures, tables, references –1” margins –12 point font Include a Title Page Include a Title Page Include Page #’s! Include Page #’s! Include section headings Include section headings Include your hypotheses, clearly stated Include your hypotheses, clearly stated Clearly delineate your goals and study designs Clearly delineate your goals and study designs Reference your work carefully Reference your work carefully

25. QUESTIONS?