R01 grant advice and random thoughts

My R01 grant is being re-reviewed in two days, and I'm having a very hard time working on the safety protocol that I came in on a Saturday to work on, so instead I made a list of some of my thoughts and advice on R01 grant writing.  

1.  Just how focused should my grant be?  I got the advice that I should really drill down into one specific aspect of my specific topic.  However, to have three aims going in exactly the same direction is really tough, and it’s unlikely that a new PI will have enough preliminary data to write an R01 this way.  My R01 that was scored reasonably well had all three aims on different aspects of the same protein, i.e., post-translational modifications, interacting partners, and enzymatic activity.  I did it this way because we had really strong preliminary data on all three of these things, but if I were to have made the entire grant about post-translational modifications, for example, I would not have had enough preliminary data, and it would have been very hard to make the aims independent of one another. 

2.  Should I propose to use a mouse model that I need to make?  Noooo! You need to have it already made, unless you are the world’s expert on making mice.

3.  Can I use extra space left over on my biosketch to address various concerns?  Yes, the personal statement can be used to highlight your training and accomplishments and also alleviate any concerns that you think the reviewers might have.  I also addressed a reviewer critique regarding potential overlap with another grant in the Research Support section of the biosketch. 

4.  Spend a lot of time writing the “Environment” section of your grant.  If you are not at Harvard, then you probably need to make this section of your grant really, really strong.  What people are in your department and university who are working on complimentary things? What seminar series do the various departments have?  Who has spoken in the past and who is scheduled that will be beneficial for your work?  Is there a journal club or seminar series specific to your research topic?  If not, start one!  One of my colleagues actually started a group on his topic for this exact reason, i.e., to be able to say on grant applications that this awesome group exists making the environment here really great.  He called it the Fill-in-the-blank-State Basketweaving Assocation and gave it a nice acronym (FBA) and invites speakers once a month to come and give a seminar that are teleconferenced to a few locations around the state. 

Titles for grants: Something new to think about

As I’ve been reading about the attack on certain NSF grants by a particular congressional republican, I’ve concluded that there’s something really important that a grant title should convey.  It should communicate why this work is important.  What is the value in doing this set of experiments?  The grants that are being attacked totally failed to do this.  If your title doesn’t provide any inkling about why anyone should care about the work, then you have failed as a title writer or your project is bad.  I don’t doubt that there is merit to each of these proposals when you dig deep into the proposal, which is what the study section reviewers would have done.  But, the actual proposals are the intellectual property of the authors and none of us have access to them.  So we’re left scratching our heads.  Careful crafting of your title is not only important to make the grant reviewers excited about your work, but these titles are sometimes the only information available on online databases that can be accessed by congressmen, tax-paying Americans, and also your scientific peers.  Why would you want to make the underlying purpose of your work indecipherable? 

I’m not saying you always have to blatantly spell out why your work is important.  For example, any title with virus, cancer, or heart disease is going to automatically be considered to have some inherent importance by the general reader who is likely afraid of each of those things.  On the other hand, if you are studying dairy farming in China and applying for a US grant (this is a real example from the article linked above) then you should have a justification in your title.   Full disclosure, I have no idea what this grant was actually about but I’m imagining something like the following titles working a little better – “Regulating dairy farming in China: Implications for international trade practices” or “Regulating dairy farming in China: Decreasing food born illness” or “Regulating dairy farming in China: A model for best farming practices.” Any one of those titles would have been quickly brushed past with no problems by the congressman and his staff. 

The more I think about it, the more it makes me angry that the authors of these grants didn’t give any thought to conveying the meaning of their work in their titles, when it is so NOT obvious (even to me, a scientist who is giving them the benefit of the doubt).  So this is just one more thing to think about when writing your grants.  Don’t be the one who is providing fuel for the republican anti-science crazies!    

What projects should a new lab be working on?

I was invited to give a talk at a local symposium, and I’m working on my presentation.  In my lab’s short history, we’ve managed to get two papers out.  One of them is so much more appealing to present to a general audience than the other that it makes me wonder whether I should be asking myself, “will I ever want to present this work?,” before starting any new project.

The project I don’t want to present was an esoteric extension of past work that I did.  The question was:  Does this protein related to the one that I study do similar things?  The answer was yes and no, and none of it was really surprising.  This was published in a decent journal and was even highlighted by the journal.  But, I’ll never ever present this anywhere because its importance would only be appreciated by specialists, and it’s boring.  Should we have bothered with this set of experiments at all? 

Well, the reason I did this work was that it was easy and quick given my expertise and tools, and it was a good way to train my technician.  It was also really awesome to get a completely independent publication out the door within six months of arrival at my new university.  And it counts towards tenure.  So yes, it was probably worth it at that point in my career.

On a sidenote, I just mentored a med student who won a fellowship to work in my lab over the summer.  I honestly had a tough time coming up with a two month project that he could actually complete.  So again I fell back on a really obvious question:  Does this homologue from another species of the protein I study do similar things?  Indeed, he got some data, and we’re repeating some experiments so that we can submit it for publication.  But again, it’s totally boring, I envision the paper writing being total drudgery, and it’s not something that would keep a seminar audience’s interest for very long. 

So what am I going to talk about???  The talk-worthy project we published was a completely new set of experiments designed to understand an unexplored aspect of our protein’s trafficking.  One of my students really just ran with this on her own as a side project.  We ended up getting cool data and what is even more awesome is that the results almost magically led us to another totally new discovery. 

So how do I predict in advance which projects will give the exciting talk-worthy results?  At face value it seems that pursuing low hanging fruit rarely gives an exciting result.  But should that exclude us from doing the more obvious work and getting easy (but only mildly interesting) publications?  The conclusion that I’ve come to is that at this critical point in my career, I absolutely need to keep the core of my lab (my grad students and technician) working on the cutting edge stuff, the stuff that I’ll want to include in my tenure talk, and maybe have undergrads or summer students pick up some of the more obvious projects just to boost our total publication output. Ask me in four years if this strategy actually worked. 

What to wear on an academic job interview if you are male

This is in response to what was written on a really great blog called The New PI Sets Up a Lab. She addresses the topic of what females should wear on a job interview and what to wear as a new PI.  

The New PI gives the advice that a woman might want to wear at least one item that expresses her personality, something that gives her some flair.  While this might work for women, and I’m not sure it does, this is terrible advice for men.  Anything strange or particularly memorable about your clothes is only going to hurt you. 

What qualifications do I have to say this?  I’ve worked in one very old-school department with lots of conservative old professors at a fancy medical school and I’ve worked at one of the world’s most prestigious institutions that was in the vicinity of four other universities.  I now work at a major university’s medical school.   The point of bringing all this up is that I’ve probably seen at least 100 job talks, particularly since I made it a priority to attend them during my postdoc, and actually paid attention to what the candidates wore.  I was also on two search committees this past year.  There are two outfits that will work regardless of what type of department it is.

What it's like to submit a paper to PNAS when you are not famous

My lab studies a protein that has been intensely researched for many years.  So we were really excited when we discovered something totally new about this protein that regulates its localization in the cell.  This is an incredibly important protein for a variety of diseases, and so we thought our findings should go to a semi-high impact journal.  I say semi-high because we don't have in vivo data and the mechanistic data that we have so far probably isn't the entire story.  Nonetheless, we made this discovery using a fancy platform technology and have plenty of experiments confirming the finding and demonstrating that it is important.

After a lot of consideration, it seemed that PNAS was our best shot because our protein is of general interest and our work reaches across more than one discipline.  Papers like ours have appeared in PNAS in recent years on less important proteins and without validation of the importance or in vivo relevance of the data.  So this is where we submitted 38 days ago.    

The reason I decided to write this post is that the review process at PNAS is not like other journals and, based purely on anecdotal evidence (my own experience and that of two other junior PIs), my feeling is that a new PI should not even bother submitting to PNAS unless they have a strong network of NAS members interested in their work, a pre-arranged editor, or perhaps have a Nature-level paper that they want to get out fast.

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.  This pretty much means that only close-to-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. 

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.

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.