Opening sentence: Frame your topic in terms of importance to NIH/foundation mission Briefly summarize current knowledge on this topic; 2-3 sentences to lay foundation for the current work Identify the critical gap in knowledge that your proposal will address and bold, italicize or underline. If a training grant, you may also highlight the need for what will be gained in this grant. Briefly outline the critical pieces of preliminary and or published data/results that form the basis for the novel hypothesis you propose to test. Bullet points can be effective here. This section should provide rationale for your hypothesis and plan to test it. Some people like to highlight the overall rationale here as well. A picture or diagram that can quickly convey the model being tested and how the specific aims relate to the overall model can be powerful if there is room and if you can make the diagram easily understandable Our central hypothesis is….(state this clearly and bold to make it easy to find). Then state that you will test this hypothesis by pursuing the following specific aims: Aim 1)xxx Give each aim a clear title that accurately conveys what will be tested (bold) Aim 2) xxx Some people like to state a sub-hypothesis that will be tested under each aim It is nice to convey how you will perform the work proposed in this aim for the study section members who will not have read the whole grant…highlight novel mutant mice or special clinical samples you might have, etc. Avoid aims that are descriptive if possible. Final sentence: Explain how completion of these aims will advance the field (fill knowledge gap) and lead to a positive impact. This should link to the significance and innovation of your proposal.