General advice

I recently received the reviews for my NIH K99/R00 grant application and was given a score of 10.  Word has gotten around among my science friends that I got such a great score, and I've had lots of requests for information on how to successfully write this type of grant.  I figured that since things are still somewhat fresh in my mind I would put together a list of the specific sections and what I think should be included in them.  This is not meant to be an all-inclusive guide or exhaustive instructions, but rather my own opinions.  See the official application guidelines found here (http://grants.nih.gov/grants/funding/424/index.htm#inst ) for the most up to date and official instructions.  I should also mention that though my proposal was scored well, I still don't know if it will be funded, especially given the current problems in congress with negotiating the federal budget.

1.      Project Summary/Abstract:  (1 paragraph)  This will be visible to the public through the NIH Reporter website ( http://projectreporter.nih.gov/reporter.cfm ) if your grant is funded.  You can use this website to see who got funded in the past and what types of projects they were working on.  I studied many of the published K99 abstracts and came up with a bare bones formula for what I think should be included.  1) State the problem/question/health concern that you will address, i.e., the big picture.  2)  Then provide two or three sentences of background specific to your project.  3)  Now state the overall goal of the proposed research in one sentence.  4)  Then state what will be done in the K99 phase.  5)  Then use a transition such as “with this information in hand, we will then…” or “having developed these techniques, we will then…” to state what will be achieved in the R00 phase.  6)  Conclude with a sentence tying all of this in to the major question from your first sentence.

2.      Project Narrative:  (2 sentences)  What are you studying and what is lacking in the current understanding?  How will your study contribute?  Of course, make these statements relevant to human health.

3.       Resources/Facilities: (1 page)  Start with a paragraph about what equipment is available in your mentor’s lab, i.e., hoods, centrifuges, microscopes, computer workstations, etc.  Then state what core facilities will be used.  Mention support staff employed by the facilities and what training they provide.  Then provide a specific list of the equipment that will be used in each core facility.  Include specific model numbers, availability of the instrument (e.g., is it available for 24 h use?), and how this equipment will allow you to accomplish specific parts of your research proposal.  

4.       List of Referees:  Name, title, institution, and city.  At least 3, but no more than 5.  One should be your thesis advisor.  Then pick the most famous scientists you know that will have something good to say about you.  Send them your current CV and a blurb about how great you're doing in terms of your science.  Also, make sure to send them the specific instructions for K99 recommendations.  They need to comment on your ability to work independently, etc.   If they hesitate even slightly, then ask someone else to do it. 

5.       Biosketches:  The K99 Candidate’s biosketch has a slightly different format than the standard NIH biosketch.  Name, title and education are in the standard order.  Next is personal statement, employment/teaching experience, awards/honors, publications, and current research support in this order.  The mentors should have their biosketches already prepared.  Customize the personal statement for them if they have not already done this for your particular purpose.  

6.       Other support:  This will come from your mentors.  It is a list of active and pending grants.  It also must include dollar amounts of each award. 

7.      Budget justification:  Your grants office should help you with specific dollar amounts that you are requesting as this is dependent on specific parameters negotiated by your institution and the NIH.  However the budget justification for this purpose is a separate document.  The following statements are what I used in mine:

Dr. Candidate will dedicate 12.0 calendar months of his effort to the proposed research project.  A fringe benefit rate of ___% was applied to  his salary.

Dr. Boss will serve as mentor for the proposed research project and will not receive any salary. 

The supplies budget will be used for purchasing…

_____is requested for the 3 years of the R00 phase and specific budget justification will be provided once an independent faculty position is obtained.  

8.       Candidate’s background: (1 page)  Start with a brief mention of research performed in college.  Loosely relate this to your current proposal, e.g., this experience gave me confidence to work with mice and helped me develop a passion for in vivo biology.  Then go on to your thesis research.  Give a two sentence summary.  Then state why this is hugely important, how many publications/invited talks/awards/accolades you got, and who is continuing this work, and whether or not since you’ve left the lab other people have corroborated and expanded upon your findings.  Also mention things like patent applications, news and views articles about your work, faculty of 1000 citations, etc.  You can basically do the same thing with your description of your postdoc work, except the research description can be more thorough since this is likely what your current application is based on.  You may also want to describe why you chose your thesis and postdoc labs as this is your chance to show how much interest you have in your field and also perhaps unique insights you brought to the group.    

9.       Career Goals and Objectives:  (1/2-¾ page)  What techniques did you learn in your PhD lab?  What new techniques did you learn in your postdoc lab?  Restate the main questions your proposed research will address and the big picture question that  you will structure your independent lab around.  How will you use the techniques you have already been trained in and what new things do you need to learn?  What qualifies your mentor, co-mentor, and collaborators to guide you in obtaining these skills – you should be quite specific here about what skills you need for each aim and exactly how your mentor will help you obtain them.  How will learning these new skills help you complete your independent phase aims? Briefly mention how your career development activities which will be listed on the next page will also help you to establish a successful laboratory.  Conclude with a reiteration of how the K99 phase will allow you to learn scientific techniques and gain knowledge necessary to be an independent leader in the field of _____.

10.   Career development/training activities:  (1 page)  Make a numbered list.  Some examples:  1)  Formal interaction with mentors, e.g., lab meeting presentations and one-on-one meetings.    2)  Formal advisory committee meetings, e.g., 3 or 4 times per year.  Having proper mentorship and oversight is a very important part of this application.  A panel of 3 or 4 people including your mentor(s) is sufficient.  The advisory committee members should be highly respected/knowledgable in your field.  Ask early for their support because they will have to write a letter for you and provide you with their biosketch.  3)  Learning new techniques.  A great way to do this is to visit another lab.   A convenient way to set this up is to learn something new in the lab of one of  your advisory committee members.  This gives them something to say in their letter of support and also will make them feel more involved in your success.  4)  Educational activities.  These are imperative!  Some suggestions for these would be grant writing courses/workshops, formal coursework at your university (you can simply audit and your institutional letter should include permission to attend these courses), seminar series that you will attend (include past topics and any pertinent speakers who are already scheduled), and attendance at conferences/meetings (give two examples of scheduled meetings that would be the type that you would attend and benefit from ).  5)  Mentored job search.  How will you go about finding faculty positions?  How will your university and mentor help you to prepare?  Will you give practice job talks?  Is there a formal mechanism for this in your department?  What experience do your mentors and advisors have in helping their trainees get jobs (make sure their letters also state these things)?

11   Training in RCR: (3/4 page)  Write up a summary of the course you attended in grad school and the course you will attend during your K99 period in order to stay current on ethical issues and standard procedures.  Be very specific about topics that have been included in the past and the format of the class.  The reviewers judge based on 5 criteria:  format, subject matter, duration, faculty participation, and frequency.  I gave a summary at the bottom of the page for each of these in a bulleted format.  This will immediately answer the reviewers’ questions about whether or not your training meets the requirements.  Another suggestion is to be sure you list faculty members (and their titles) who have given lectures or led discussions in the past.

12   Mentor letters: (5-10 pages)  Ask the mentors to write the letter and let you tweak the wording.  They should describe what you’ve done in their lab and how important it is.  They should also include any mentoring you’ve done within your lab.  They should also clearly state where funding will come from for your supplies during the K99 phase.  Any overlap in terms of their own grants should also be explicitly addressed and they MUST state that you will be free to take this project with you to your independent lab.  They can also provide a list of publications they think will result from your work including the estimated impact of each paper.  They should also list the same career activities that you outlined in your proposal but under each they should state what their role will be in helping you to succeed.   They must also state what percentage of your time will be devoted to research and that you won’t have teaching responsibilities.  They should conclude with a summary of their own past mentoring accomplishments and their willingness to help you in the same way.  

13.   Description of Institutional Environment:  (3/4 page)  Describe how great your university is.  What makes it unique, particularly for your field?  What seminar series do they have?  Who has presented in the past and is scheduled in the future?  Who are the relevant famous people in your department or university – list these famous people as they are likely the ones who draw the famous seminar speakers, etc.  What seminar series can you participate in to gain practice?  Of the coursework you proposed, explain why this course is particularly great at your university.  End with a mention of the shared resource facilities that you will use and direct the reviewers to the list of equipment that you included in the resources/facilities section.  

14.   Letter of institutional commitment:  (2 pages)  There is probably a standard template that your university uses for this, but you should ask to customize it for your proposal.  It needs to state that you will have no/minimal teaching requirements.  It needs to state the university’s commitment to career development, e.g., by having workshops and seminars and a postdoctoral association.  It needs to state resources that are available to you, i.e., resource facilities and equipment specific to your proposal.  It needs to state that you will be able to attend the courses that you have proposed.  

15.   Aims page: (1 page)  This needs to have specific sections and I’ll give my advice for each one.  Context:  Write a short paragraph with background about the big picture question funneling down to what your question is or what is still not understood.  Summary:  Summarize your aims being sure to explain how skills learned in the mentored phase will be applied to the independent phase.  Next list the actual aims in numbered format divided into independent and mentored phase.  Have no more than 3 aims total and not many subaims as being overly ambitious is a huge problem for this type of grant.  Outcomes and impact:  Write a short paragraph hypothesizing what your findings will be.  You can even bold your overall hypothesis.  What fields of biology or disease conditions might your research impact?  How will the research impact your longterm goal of understanding question xyz in your own lab?

16.   Significance:  (1/2 page)  This needs to be related to human health.  Describe the disease state that your research deals with and provide a statistic about how important it is.  Then describe why current treatments are inadequate.  How will your research bridge this gap?  How does your research in addition to potential clinical applications also lead to advances in our understanding of basic biological phenomena?

17.   Innovation:  (1 page)  There should be something innovative in your methods for you to write about here.  If you are not using completely novel technology you could highlight the the combination of classical methods or the application of these methods to your novel question.  This is also a good place to include some preliminary results showing how great your methods are.  Now move beyond the methods themselves and think about your research.  Why has no one done this before?  What gives you a unique advantage over others who may be asking similar questions?  What unique or interdisciplinary insights might your mentors and advisors provide?  What paradigms will be shifted if your hypotheses are correct?

18.   Approach:  (7 pages)  This will be unique to each proposal but a good rule of thumb is that you should have at least some type of preliminary result for every aim, even those in your R00 phase.  If you’re proposing to use stable cell lines, show that this is possible to generate.  If you’re proposing qPCR, show that the primers have been validated.  Show that all of the plasmid constructs you need to use have been generated and that the proteins are expressed.  If you are going to be learning a specific technique from another lab you could even use one of their figures (do this once at most and only if warranted, and make it blatantly obvious that you are not trying to take credit for their work).  If you are making a mouse, show that the targeting constructs have been generated.  Feasibility is very important and the more preliminary reagents you have developed, the better.  Also, for your R00 phase aims, you may want to point out if any of the aims or subaims are exploratory and could provide results for future R01 applications.  I included a color-coded flow-chart explaining my proposed experiments and also the technique that would be used and highlighted which techniques were something new that I needed to learn how to do in the K99 phase.    Conclude with an overall summary section that should be one paragraph that briefly describes how important your work will be and how your mentors’ guidance is imperative to your success.      

19.   Biohazards:  Specific to your proposal.

20.   Data/Resource Sharing Plan:  State that you will publish your results in a timely manner, share your reagents upon completion of appropriate material transfer agreements, and that you will present results in meetings. 

General comments:

1.  Mentors:  You need someone who is extremely well respected in your field to serve as a mentor.  If your current mentor is too junior, you absolutely must have a co-mentor.

2.   Use Adobe InDesign software to format your grant.  Type everything in Word and then as a final step add the text and images using InDesign.  Adding images in Word is a nightmare and you can never position things exactly where you want them. 

3.   Coordinate mentor and co-mentor letters so that they say the same things regarding career and training activities.  

4.  I found this blog to be especially helpful when I was writing:   http://chemicalbilology.blogspot.com/2008/06/how-to-put-together-your-life-and.html

5.  The author of the blog above also started a K99/R00 message forum that is full of good information:
       http://k99r00-land.motionforum.net/forum.htm