Principles of Grant Writing

1. Principles of Grant Writing Allison B. Reiss, M.D. Head, Inflammation Section Winthrop University Hospital

2. Getting Started • Find a mentor • Select an area of interest • Read the literature in the field • Ask questions • Look for gaps in knowledge • Come up with a novel idea • Generate a meaningful hypothesis • Secure collaborators for areas in which you lack experience/training

3. Being a Credible Candidate- Your CV • Gather preliminary data • Publish with your mentor • Write review articles or book chapters • Present abstracts • Attend scientific meetings in the field • Network • Join committees • Follow NIH biosketch format

4. Choosing a Starter Grant • Start modestly and expect criticism • Local societies such as LI Chapter of Arthritis Foundation or American Heart Association • Fellowship grants with mentor • R03- small grants for new investigators • Small specialized foundations • Always adhere to the requirements of the grant solicitation.

5. Getting Organized • If it is your first time start 3 months ahead! • Read the instructions for the specific application • Be sure that you qualify- stage of training, academic appointment, degree necessary, citizenship requirements • Be sure that your grant fits the stated objectives of the program • Make a checklist of all the things you need to accomplish- you can have the body of the grant completed, but without the ancillary paperwork you will miss the deadline!

6. Title • Come up with an attention-grabbing title that communicates the key points and focus of the application. This is your FILM and you want to win the Oscar for best picture!! • Reviewers may have to judge their ability to review an application based solely on the title. They are often asked to rate their expertise from 1 (this is my field) to 5 (I am clueless) based on title alone or title and abstract • You do not want your application to be read by someone who will not be able to understand and appreciate your ideas.

7. Sections of the Grant • Abstract • Specific Aims • Background and Significance • Preliminary Data • Research Design and Methods Other (depends on grant) • Human subjects • Vertebrate animals

8. Specific Aims • These are the objectives of your research proposal • Most important- set the tone for the whole grant • First thing reviewers evaluate • Should be driven by a strong hypothesis • Usually two or three per application • Should be focused and coherent

9. Specific Aims- Format • State the aim in bold type- be succinct • Add a sentence or two describing the rationale for the aim and the methods to be used. • The Specific Aims should not take up more than one page. • Do not be diffuse- aims should be feasible and relate directly to hypothesis • Do not turn the aims into a list of experiments or your grant will be triaged!

10. Specific Aim Example from NIH-Funded Application entitled “Immunological Mechanisms in Premature Atherosclerosis” • Examine the impact of immune reactants in the circulation of SLE patients on cholesterol homeostasis in cells relevant to atherogenesis. Effect of SLE patient plasma on expression of proteins involved in cellular cholesterol uptake and excretion (27-OHase, ABCA1, ABCG1, LOX1, LDL receptor, scavenger receptor) is assessed (Western blot, Quantitative real-time reverse transcription-polymerase chain reaction [QRT-PCR]) in the THP-1 human monocytes and human arterial endothelium. Relative contribution of IC-C1q and IFN-gamma present at elevated levels in SLE patient plasma to the decrease in 27-OHase message is evaluated by exposing cells to SLE plasma with/without specific immunoneutralization (achieved by pre-incubation with anti-C1q receptor antibody, anti-IFN-gamma antibody and anti-IFN-gamma receptor antibody).

11. Background and Significance • Your chance to set the stage- be convincing, compelling, succinct, thorough. • State problem to be investigated and rationale for proposal. Logical persuasion. • The scientific question- what has been published by others in the field? Show that you have a good command of the current and ongoing research in your field. • What is not known and why is it important to fill in the gaps or resolve discrepancies? • How will your proposed study advance knowledge and resolve issues in the field- groundbreaking?

12. More on Background and Significance • Demonstrate that accomplishing your aims will provide new information that fills in crucial holes. • Have you already made contributions? • Emphasize the innovative nature of the work and impact you have made or will make. • Be sure to reference prominent scientists in the field- they may be reviewing your application! • Don’t write a review article- you need to save space for your methods section.

13. Preliminary Data • Your opportunity to show that you are technically competent to design and carry out meaningful experiments. • Data from replicate experiments with good reproducibility, small error bars, carefully analyzed, properly controlled. • You must present results clearly, completely and objectively. • Charts, graphs, tables, statistics are key. • It is crucial that your data provide a sound basis for the proposed hypotheses. • Evidence that the proposed techniques will work and that you can perform them.

14. Research Design and Methods • Heart of your plan- describe your methods and experiments in detail. • Correspond methods to each aim in turn. • Exactly how results will be collected, analyzed, interpreted. • Include the results you expect and their significance and relationship to your aim/hypothesis. • Describe what it will mean and what you will do if you get unanticipated results.

15. Research Design and Methods cont’d • Discuss potential difficulties and limitations and how these will be overcome or mitigated. Need alternative approaches. • Specify animal models, exposure times, reagents and how you will obtain them, statistical analysis methods, and other details. • Are these the optimal most suitable methods to compile the data you need? If possible, discuss other methods and justify your choice. • Give context- don’t just list methods. Are methods direct extensions of your preliminary data? • Include a timeline.

16. Pitfalls and Alternatives • The experiments proposed are a logical extension of our previous work in which we demonstrated a highly significant downregulation of 27-OHase mRNA expression in cultured human arterial endothelium after 3 hr of exposure to SLE patient plasma (see Preliminary Studies). I have extensive experience in formulating and executing this type of study. The study will be blinded so that the person measuring 27-OHase levels will not know which human plasma and antibody conditions the cells were subjected to. That information will be kept confidentially with numerical coding. • The following difficulties may arise: 27-OHase downregulation by SLE patient plasma may not be blocked by blocking C1q or IFN-gamma. SLE is characterized by the production of multiple autoantibodies. Although the pathogenesis of SLE remains enigmatic, autoantibodies against dsDNA and ribonucleoproteins, deposition of IC, complement activation, and leukocyte infiltration are thought to represent a consequence of immune dysregulation in this disease. Thus, a number of factors in plasma are potentially involved in regulating the 27-OHase. If blocking IFN-gamma and IC fails to ablate downregulation, we will look at downstream effectors in the complement cascade (i.e. complement components C3b, C3bi, C5a and their receptors or C5b-9). This will be accomplished using antibodies to CR1 and CR3 or the receptor for C5a or antibodies to C3b, C3bi, or C5a.

17. Research Environment • Must establish that the facilities, resources and personnel are favorable for execution of the project aims. • Describe the scientific environment and emphasize the features that you need and their ready availability. • Institutional support- letter from chair/director • Collaborators/consultants- get the best. Most are approachable and helpful. Their strong CVs will enhance you!

18. Human Subjects • Can be tricky and sensitive • Be sure to stay within HIPAA guidelines • Minimal discomfort/risk to patient • Confidentiality and privacy of subjects must be maintained • Informed consent • Participation must be voluntary- discuss risks and benefits

19. Elements of Human Subject Study • Description of population to be studied • Description of method by which subjects will be identified and recruited • Sample size • General purpose of the investigation • Source of research material • Subject inclusion criteria • Subject exclusion criteria • Duration of study • Inclusion of women, minorities • Inclusion of children • Data and Safety Monitoring Plan

20. Budget • You need to know your stuff! • Get salary guidance from human resources- many grants limit salary • Must look up expenses of your major supplies such as glassware, cells, enzymes, antibodies, assay kits, animals and their chow/care etc… • Can get this info online or in catalogs or call the company. • The higher percent effort you can give the better.

21. Grant Killers- Reviewer Turn-offs • Significance is unclear: “So what?” • No innovation is noted • Proposal is not hypothesis-driven, but is a “data gathering exercise” • Over-ambitious, dense, diffuse • Preliminary data is not convincing/clear-cut • No back-up plan • Would never pass IRB • Lacks statistics, power calculation

22. Proofreading • Final draft of a proposal should be proofread by someone other than the primary grant writer. • Ask other successful investigators to proofread your grant and provide feedback.  • Make sure your grant is grammatically correct. • Check spelling and punctuation. • Look for errors in logic or presentation.

23. Submission • Check the deadline. Late proposals not considered. • Make sure font size, margins and length are within guidelines. • Page limitations • Administrative approvals-Sponsored Programs will help. Let them know early. • Letters from consultants/collaborators • Manuscripts/publications • Cover letter • Electronic or delivery service or both? File format. • Web sites can get jammed near deadline.

24. Good Luck!! If you need help, you can contact me through AFMR