Saturday, July 12, 2014

R01 update: the pain of a close score


I got my score for the R01 that I wrote on my lab's main project.  The scores were awesome.  They thought the grant was significant and innovative.  They thought my expertise was perfectly aligned with the proposed work.  The scientific environment got mostly perfect scores as well.  They thought the aims were great.  The reviewer concerns were minor at best.  On one hand this feels awesome, but on the other hand, it means nothing, because I still didn’t meet the payline, even with the ESI bonus.  This hurts even more knowing that my score is one of the best anyone in my department has received in the past three years (including all the funded projects).  This pretty much means that only perfect scores will be funded this round.  The situation just seems impossible.

My dept chair was quite a bit more upbeat about this than me.  She said there was very little chance that the study section was going to give me this grant on the first try anyway when I still have a few more months of funding left, but that I should get it on the next try.  I didn’t think study sections were supposed to consider current funding, but then again, in this funding climate, how could they not?  She also told me to look at this as an opportunity to stop and think a little deeper about my research, and really bring out the therapeutic future potential in the resubmission.  I guess that's good advice.    

My program officer said something similar about select pay.  She loved my grant and said I was a great candidate for select pay given my great score and that most of the critiques could be responded to simply by adding text.  However, with the remaining months on my R00 grant, she said I would likely not be competitive for select pay in the eyes of the council, because this usually goes to labs that are about to shut down due to lack of funding.  So obviously things could be worse, but it still stings.  

So I’m gearing up for a resubmission.  ESIs can resubmit past the standard deadline for review in the very next cycle.  Since my first submission, we’ve published a paper that addresses many of the questions in Aim 2, so I now have to write a new sub-aim or craft an entirely new aim.  I feel like I have to come up with something so practical and feasible that there can be no new critiques, but then this means that it will probably be boring.  Everything I want to write about has a catch.  In vivo experiments, using a new type of primary cell, or using a new technique would all open up a whole new world of possible concerns from the reviewers.

So this means my complete blog post on writing an R01 is still postponed until further notice.  If you need me, I’ll be brainstorming in my office all weekend. 

Saturday, April 12, 2014

Why I hate career panel discussions


I’m at a very large university and in the past year, I’ve been asked to be on three different career panels for three different student/postdoc groups.  I was recently on a committee for our departmental retreat and the committee chair proposed doing yet another one of these career workshops for the students.  I tried really hard to convince my colleagues that we could do something better, because I’ve really come to hate these types of career panels.  Here are some of the reasons.

1.     People are chosen/invited because they have really interesting careers.  Inevitably they got these jobs because they knew somebody or were in the right place at the right time.  Therefore, they rarely have anything useful to say in terms of how you prepare to get this type of job. 
2.     I was reprimanded by my department chair for giving an honest assessment of my own accomplishments during graduate school and postdoc, which included lots of papers and fellowship funding.  I also had two glamour publications during my postdoc, which I believe is now an absolute requirement for getting a faculty position at a top university.  My chair was truly angry at me because he thought I was discouraging the students from taking an academic path.  Are we supposed to lie to the students, when in reality, maybe one or two of them will ever get a faculty position? 
3.      Someone at these panels always says something like, “embrace your failures.”  To me, this is the most smug and condescending thing that someone who has already made it could say to struggling students.  This is really easy to say in hindsight, but totally stupid to say to people in the midst of trying to find their way. 
4.     The second most common thing that I hear is that you should have a file of all your accomplishments to look back on when you feel rejection to try to make you feel better.  Again, I HATE THIS ADVICE.  The last thing I want to think about when I’m feeling bad is how great I USED TO BE.  The depressed mind is incapable of looking on the bright side, and I just don’t understand why we can’t say it’s ok to be sad and disappointed.  This is what I tell my own graduate students.  Give yourself a day or two to be depressed.  Then force yourself to write out a plan for overcoming the roadblock.  This is the only thing that can snap me out of this type of depression, and it actually makes me feel worse to hear this terrible advice to "think happy thoughts" repeated over and over again.  Even if the new plan is not what you originally thought was optimal, it will instantly make you feel better to have a course of action.   

Saturday, March 22, 2014

My R01 advice so far…


I’m not quite ready to write up an exhaustive guide for what I think should be included in each section of an R01 like I did for the K99/R00 application, because, well, honestly, I haven’t gotten an R01 funded yet.  I have now submitted two completely different applications.  One was scored, but not in a fundable range, and the second will be reviewed in June. 

So what did I learn from my first unfunded application? 

Well first of all, you really have to think about whether it's worth the time if it's not a clear super-slam-dunk. It really seems that every star has to align for you to get funded right now.  For me there were several problems with my grant that I did realize beforehand, but, because I was getting such great feedback locally, I suppressed my gut feeling about these things. 

1.  I proposed to use a mouse model that we are in the process of developing.  All three reviewers basically said that preliminary data with the mouse was absolutely necessary and one even said that the relevance of the entire grant was in question until this mouse and the preliminary data were in hand.  I actually think I would have been better off leaving that one small subaim out of the grant altogether.

2.  This was a new direction within my field that I have not published on specifically.  I actually got 1’s and 2’s for my score as an investigator, but then there were hints of skepticism in the critiques of the approach, which I think would have been eliminated had we had at least one publication on this exact topic.  I will not be resubmitting this grant for at least a year so that we have both the mouse and a published paper. 

3.  A clear focus on a specific disease seems to be absolutely essential.  I thought a strength of my grant was that what I am studying is an entirely new aspect of a protein/pathway that is so broadly important.  However, without a very specific disease model system, our work came off as generating knowledge for knowledge’s sake.  This is a little frustrating that they weren’t seeing the big picture, but on the other hand, I see how it’s easier to grasp, and easier to justify spending the money when there’s a specific disease being worked on.    

4.  Adding senior PIs onto your grant does not necessarily make you more credible. It just makes the reviewers angry. “Bloated” budget or some variety of that sentiment was used by all three reviewers.  This came out in the critiques of the approach.  Any salary support for people outside of your lab has to be absolutely 100% critical to you completing the research.  Mentorship or advice on certain techniques doesn’t cut it.  They need to actually be doing something substantial to get any salary support.  I was left with the feeling that a simple modular budget for me as a new ESI with no paid collaborators would have made them much happier. 

The last thing I’ll say is that while this grant was not funded, I learned A LOT that I applied to my second application.  This new application is on our bread-and-butter topic, the one for which my K99/R00 was funded.  This one was so much easier to write because we have publications, lots of preliminary data, and a very clear disease model.  The tricky part for me was making it completely different from my R00 aims.  I was hesitant to submit on this topic earlier because I assumed that whatever I proposed, the reviewers would say, “well shouldn’t you be doing this new and exciting stuff already with your R00 money?”   However, this view changed when I realized that one of my fellow K99 recipients had landed an (enormous non-modular) R01 on his first submission in the first months of his faculty position with the same overall goal as his K99.  Upon a very careful read of his grant summaries, I realized that the aims of his two grants were indeed distinct even though the goal was the same.  I decided to take the same approach.   Over the past two years in my own lab we’ve made a lot of progress and have developed some new directions, so I made absolutely sure that my aims were completely different in the two grants.   Stay tuned for the June reviews.  I’ll either be writing up my guide to writing R01s or frantically working on a resubmission. 

Monday, August 5, 2013

Update: I did get a faculty job!


Since I haven’t updated this blog in a while, I’ll start by saying that even with a K99, a good number of publications, and a pretty famous postdoctoral co-mentor, I only got two interviews from the roughly 100 applications I sent out. 

I wrote about my first interview in my last post, and even though I did like the school and the people there, it was in a city that is economically depressed and far away from family, and overall made me feel anxiety about potentially having to move there.  What was even worse is that I didn’t hear anything about their hiring process for months. 

I felt defeated and scared to death the day that I had to email the NIH and ask for an extension on my K99 because I hadn’t secured a faculty position. Luckily, the people at the NIH were totally responsive and reasonable and gave me up to a year extension for the due date of submitting my R00 application.  However, this did not come with any more money.  So my mentor had to start paying my salary again, which meant a major pay cut and a major blow to my self-esteem.  

I was still clinging to the notion that the perfect job in my dream east coast city was going to appear even though I knew the hiring season was basically over.  I was checking job postings multiple times per day and a very late job posting did appear at a major university in a Midwestern city that I had travelled to many times during my childhood.  Leaving the east coast was something I was desperately trying to avoid, but I felt like I at least had to apply since it was a really great school.  I sent out this one last application, six letters of recommendation (because they said “at least three”), and mentioned in my cover letter that I had visited many times and had family in the area. 

Within a week, I got a call from the department chair inviting me for an interview. Scheduled for four months later.  Yes, you got that right.  Four months.

I thought all that time was going to drive me crazy, but I used it to get another paper published and to get a new large-scale data set to use as preliminary data for future experiments to talk about at the end of my job talk.  And as for the job talk, I totally re-vamped it and practiced it to death!  I practiced individual sections of the talk until they were perfect, and then went through the whole presentation out loud (for my dog) every single night the week before the interview.  And I got Ambien so that I wouldn’t be staring at the ceiling with a crazy adrenaline rush all night for this interview.

I was still unsure about how excited I was to actually work at this university, but by this time I had found out that the first school had hired someone else.  They didn’t actually tell me this.  As a matter of fact, officially they told me they were still in deliberations, but I found their departmental meeting minutes online, which clearly stated who their first choice candidate was and that she had accepted the position.  This was extremely frustrating.  But, it also pushed me to do really well on my next interview.   

They flew me out the day before the interview and I went walking around the city.  I was blown away by how cool the vibe was in certain neighborhoods.  Having lived in Brooklyn for a long while, I couldn’t help but draw parallels.  This was a good thing, and made me feel like living here could be more of a possibility than I initially thought. 

Maybe more importantly… I killed the job talk, and really liked everyone I met.  The department was fantastic and full of outstanding science.  My potential lab space and office were also top notch in the best science building on campus.  Core facilities were unbelievable.  Plus, after meeting everyone, it was perfectly clear to me why they jumped so quickly to interview me.  My research fit amazingly well into this department in so many ways, yet in other ways filled a gap that they were missing. 

When I got back to work, I immediately emailed the chair about how excited I was.  I was their last candidate to be interviewed and within a week I was invited for a second interview and was sent a draft offer letter. 

Somehow things were working out in ways that I never would have predicted, yet I was really happy about it.  Another strange thing that happened is that when I emailed the chair from the first school to tell him I had a job offer that I was going to accept, he actually called me the next day and gave me a verbal job offer as well.  I have absolutely no idea why having another offer suddenly made me a more attractive candidate, but I politely declined.

I went through the second interview, negotiations on startup, moving, and have been here at my new university for almost a year now.  Time flies when you’re really busy!  I got my lab set up and recruited two lab techs and a student.  I think we’re going to get a short paper out pretty soon, and I even submitted my first R01 application this year.  The more, I think about it, the more blog posts I need to write!  Depending on my score, I’ll definitely do a post about writing an R01.  It’s a whole new ball game compared to the K99 application.  

Anyway… I just wanted to write an update to let those on the K99 path know that sometimes faculty job searches do turn out well, even if you end up in a totally unexpected place.

Monday, January 16, 2012

First Job Interview

The blogs were right when they said that an academic job interview is possibly the most exhausting experience of your life.  I had a full day of travel complete with a three hour time difference that then left me wide awake with adrenaline flowing at 4am both mornings. (I had been getting up at 7am everyday the week prior.)

As for the school, I had a great experience and was extremely impressed with everything about the institution.   The department chair was absolutely inspiring and I left feeling like I could totally be successful there.  More importantly, I left feeling like I was exactly what they were looking for and that I'd have a job offer in the mail the very next day.  However, I think their goal is probably to make everyone feel this excited... and I'm still waiting for that offer.

The interview days involved about a dozen meetings with deans, dept chairs, everyone on the search committee, and all the hot-shot faculty members plus two breakfast meetings at my hotel, a lunch meeting with students, and a big dinner with faculty at an Italian restaurant.  I was literally delirious during my research seminar because it was at the end of the first day and I somehow finished about 10 minutes faster than any of my practice runs.  But, I had a lot of questions so I think it was ok.  Luckily the chalk talk was early the second day so I was a little more composed for that.  It's really true that you can almost instantly tell who is on your side in the chalk talk and who is not-so-interested in hiring you.  They either asked questions that were genuinely to help them understand or suggested other approaches that might help to get the research funded, OR they asked irrelevant/tangential questions to try to confuse things or to get me to argue with them. 

Before the interview, I read a lot of the articles and tips on academic interviewing including all the of the blog entries aggregated here at bluelabcoats, but I thought I'd make a list of a few more things that I learned.

1.  Extensively research the people you're going to have meals with.  You should absolutely never run out of questions or things to talk about.  I think people are most excited and find YOU most interesting when you ask them about their own research.  This is what I tried to do, but I often found myself falling back on general questions about the school because I didn't always know enough about their specific area of interest to ask intelligent follow up questions.  So I wish I had read a few of their papers a little more in depth.

2.  Have a hundred questions ready for the students.  Even if you think you have a huge list of questions, think of more.  The students were really shy at first so my mental list of questions for them was exhausted very quickly.  Luckily some of them started asking me things about the job search and this led to a discussion about their own job prospects and advice I had for them in choosing postdoc advisors, etc.  This became infinitely easier when it turned into a conversation, but I'm not really sure how that can be forced or planned.  Just have lots of backup questions for them.

3.  Have a list of required resources ready even if you've been told that they won't ask for this until the second interview.  Also, you should know EXACTLY what equipment is available in core facilities.  This was one of the first questions I was asked - "Exactly what resources do you need and how will you utilize the instrumentation available in our core facilities?"  Luckily I did research on the core facilities and was able to answer this.  Almost the exact same question was asked again during my chalk talk.     

 4.  Don't feel embarassed to ask to use the restroom.  I was never once offered a chance to get a drink of water or go to the bathroom.  Bring a bottle of water for yourself and maybe something sugary to eat right before your seminar. 

5.  I was asked multiple times if I was married or had a family.  This is illegal and shouldn't influence their decision, but be prepared with an answer, because they will ask. 

6.  Every person you meet with will have a different way of dealing with their 30 minute meeting with you.  Some will give you a 30 minute seminar on their work.  Some will expect you to ask them questions for 30 minutes.  Some will ask you questions about your work and some will also ask you really aggressive questions about your research and about your interest in the school.  One professor repeatedly asked me in different ways about how interested I really was in working at their school and moving to their community.

7.  For the chalk talk you should know exactly what staff it will take to complete your proposed research aims.  What will be the first project you assign to a grad student or technician?  Also know exactly what institute at the NIH and even the specific study section where you will send your grant.  I was told that I should outline my first RO1 grant for the chalk talk, but at the end we still had five minutes and I was then asked to quickly outline a second RO1, and then what the subject of a potential third RO1 could be.  They also asked if I had researched any new investigator grant awards that I could potentially apply for.  So also be aware of specific foundations that you can apply to.

That's all I can think of for now, but I'll add to this list as I remember things...

Monday, January 2, 2012

Update on the Faculty Job Search

I still get quite a lot of hits for this blog, so I thought I should give an update and let you know that my K99 grant was in fact funded.  I'm currently trying to land the elusive faculty position because my K99 time period is only 1 year.    I sent out about 50 applications as I'm not really limited geographically and my research can fit into a lot of different settings.  However, this application process has been one of the most humbling experiences of my life.   In the days before Christmas, I received outright rejections from more than half of the departments I applied to.  It just goes to show that a good publication record and a history of funding is still not enough.  The letters often commented on how they received between 400 and 600 applications for the position.  Those are pretty terrible odds. 

However, there is still some hope.  I've had 5 requests for reference letters from places that I'm excited about and still waiting to hear from.  Plus,  I do have one (and only one) interview scheduled for later this month at a school that I'm getting more and more excited about the more I read about it.  I'll let you know how it goes.

Wednesday, March 30, 2011

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