Specific Aims

1. Specific Aims Douglas Marchuk, Ph.D. Grant Proposal Writing Class

2. Importance of Specific Aims • The specific aim section is the single most important section of the grant proposal. This single page will make or break your application. • When the reviewer has finished reading this page, he will already have a preconceived notion of the quality of the proposal, and is likely to already have a score in mind! • This page is likely the only section other than the abstract that everyone on the review panel will read! Thus this one page has the most influence on your score. • It must be written with the above in mind. Panel members will be reading this page while simultaneously listening to others speak. It cannot be overly detailed and complex.

3. Importance of SA page cont’d • The SA page becomes the template for the Research Design and Methods section. • Thus, it directly influences the next most important section of the grant. • It is the document that you will show to your colleagues for comments and suggestions. • It is the document that you will send to Program Officials to help determine whether the proposal is responsive to an RFA or PA. • It is the document that you will send to the SRO to decide whether you have found the best study section.

4. Specific Aims Page as a partnership with the reviewers • Think of the Specific Aims page as a partnership with the reviewers who will represent you at the panel review meeting. They have read your proposal, the others haven’t. • The Specific Aims page is a framework that the reviewers will use to hang the details of the proposal for the rest of the panel.

5. A template for the SA Section 4 paragraphs or subsections • Introductory Paragraph • What, Why, Who Paragraph • Specific Aims “List” • Specific Aim 1 will test the hypothesis that… We will employ our mouse model that enables us to distinguish… • Specific Aim 2 will test the related hypothesis that… We will employ an in vitro assay that we have developed in our laboratory that enables us to accurately measure… • Payoff Paragraph

6. Introductory Paragraph • Opening sentence. Establish the relevance of your proposal to biology or human health. Grab attention here. • Next: briefly summarize the state of current knowledge for those in the field (perhaps your 3 reviewers) as well as those outside it (perhaps the rest of the panel). • Not a comprehensive review, but a few sentences that summarize the most important points • Also serves to set the stage for the gaps in the knowledge. • What are the gaps in the knowledge? Or if hypothesis generating, what is the need? This sets up the logic for the proposal. Make it simple and direct. • Why is this unfilled gap or unmet need a problem? How does the gap block advancement in the field?

7. What, Why and Who Paragraph • What is the long term goal of the project? This relates to the continuum of research that you envision over the course of your career. • What is the objective in this particular application? • What is the central hypothesis of this proposal? • How was it formulated? Preliminary data from you or from the literature? • What is the rationale? What will be possible after you complete the work? • Why are you the person to do it? What unique resources, expertise, preliminary data do you have that makes you the one to do it?

8. Specific Aims List • Each aim should convey why the research is being proposed. • Each aim should test a specific part or aspect of your overall working hypothesis. • Not “ I will determine the mechanism how gene X leads to outcome Y”, since this does not show the hypothesis, and is open-ended. • Instead, “My working hypothesis, based on our preliminary data, is that NFkB regulates the expression of gene X, thereby beginning a cascade of events leading to outcome Y. • Then briefly explain what you will do. Essentially make the why the most important point, then the what or how you will do it.

9. Example of an Aim • The working hypothesis for this aim, based on data that will be presented under Preliminary Studies, is that specific regulatory alleles of the ALK1 receptor explain the development of brain arteriovenous malformations. The approach used to test this hypothesis will be comparison of genotype allele frequencies in a matched case and control population.

10. Interrelatedness vs. Dependence • Each aim most logically flow from the previous one. • But no aim can be completely dependent on an expected outcome of an earlier aim. • Expected outcomes are not guaranteed in science. • If this occurs, the other aims cannot be completed. This would be considered a “fatal flaw” in the proposal.

11. Overall Hypothesis Aim 1 Aim 2 Aim 3 time • Aims should be interconnected but not dependent on the successful outcome of another aim. • EXAMPLE: Bad – Aim 2 cannot proceed until the studies in Aim 1 are completed. • Worse yet, Aim 2 may be irrelevant if the expected outcome of Aim 1 is not realized. • Good – Aim 2 proceeds in parallel with Aim 1 and findings from Aim 1 • might direct future studies in Aim 2 or 3. • In the end, aimsrelate back to the overall hypothesis. Figure from Brian Wamhoff UVA

12. Payoff Paragraph • What is the return on the investment in this research? • What are the expected outcomes? • How is this innovative? Need not be innovative in technology or methods but at least conceptually driving the field to new areas. • How does it fill the gap in knowledge and where will this now let us go?

13. Linear Progression of Logic in Specific Aims page Gap Objective Central Hypothesis Specific Aims Expected Outcomes

14. An example in outline form A. Specific Aims Phenomena X or disease X is… A characteristic feature of this process is… Although ABC has been shown to… it is unknown whether… Preliminary studies[orRecent studiesfrom our lab]show that… However, it is unknown whether… Therefore, the overall hypothesis is that… This hypothesis will be tested by the following specific Aims: Aim 1 will determine… Aim 1 will utilize X and Y methodology to… In Aim 1A we will… In Aim 2A… We hypothesize that… Aim 2will determine… Aim 3 will determine… The results of this study will lead to a better understanding of….

15. Tips on Aims Courtesy of Brian Wamhoff UVA • If the Aims are not interconnected, the project can be perceived as “over-ambitious and unfocused” where each Aim is probably a proposal in itself. • If you cannot keep you Aims page to 1 -1.5 pages, then you are proposing too much and the grant is probably “over-ambitious and unfocused”. • If the proposal request funding for 2 years, then the probability of achieving the Aims should be within 2 years. Proof that the applicant has thought this through is usually addressed by Predicted Results/Interpretation of Results and with a timeline or timeline statement. • The standard rule of thumb for a pre/post-doc fellowship is two Aims. It is OK to propose three Aims. However, if Aim 3 will not fit into the 2 year timeline, but it is clearly a logical progression of the studies, then simply state: • Aim 3 is to determine the… Although this Aim does not fit the time frame of this proposal, future studies by the applicant will… • Descriptive Aims: If the Aim cannot have a stand alone hypothesis, then it is probably “descriptive”, not “mechanistic”, and may be detrimental to the success of the grant. Example: gene arrays as an aim.

16. Specific Tips on Aims • Never propose to make a knockout mouse or transgenic mouse for a 2 year proposal. If you do not have the mouse in hand, you are not ready to submit a proposal. These proposals are viewed as risky, especially during tight funding periods. If you have the mouse in hand, show preliminary data. • For example, you received or made a mouse null for gene X. Show a Southern blot with the X deletion or histology images that show a phenotype, etc… • Developing a new technology is risky. For example, if you are proposing to measure blood flow in your knockout animal with a new technology, but Aim 1 is to develop or even complete the technology, this will probably not get funded. • Use tools, models, animals that are readily available to you.

17. Concordance of Aims and Abstract • At many institutions, the title page (which includes the abstract/summary) and the budget are due in the grant office very early on in the process. • However, the proposal and even the aims may change drastically over time with revisions etc. • The original abstract/summary may not faithfully reflect the aims and scope of the final version of the proposal. • If possible, reread the abstract when the proposal is complete, and if necessary, revise it. • The same often holds true with manuscripts!