Payline limbo: should I revise and resubmit my K99?

We interrupt this regularly scheduled period of non-posting (due to overwhelming busy-ness in work and life, as usual) to share a K99-related question that might be particularly useful to K99 applicants during this waiting phase.

The following question came up at the K99/R00 forum (some details redacted):

I submitted to my K99 to (Institute X) and got a score of (Good Score). Institute X just posted the funding policy for FY11 and it was (slightly >Good Score) for K99 (5 points lower than last year). I called my PO and she said it is "not (definitely) 'fundable', nor it is 'not fundable'." (Ed: i.e. in the grey zone) She suggest me to prepare for revisions if I have time and it wouldn't affect my chance of getting funded for the first submission. It seems very likely that I would get funded on a second trial. The trick is I have already submitted my job applications and get an interview from a top research university and hopefully more to come. Should I wait for another two years to go for a job? Or I should quit now? Very frustrated and confused....

I wanted to share my response with readers here:

Hang in there! Limbo land sucks. The key to understanding your PO's code-language is that she is trying to encourage you without getting herself in the position of having promised funding to someone, from whom she then has to take it away. Since you are under the payline, you very likely might get funded, but since Congress hasn't passed the budget for next year yet, she doesn't know how much money she'll have in her bank account and they might pass a budget that makes things a lot harder for her to fund you that close to the payline. She's not trying to make you confused, she just can't commit until she knows her budget.

My advice is always YES to prepare revisions for resubmission. If you don't prepare a revision, and then you don't get funded, there's no way you can get the grant. But if you do prepare a revision, and DO get funded this time, then oh well, you have put some thought into what you might need to change once you actually start the research. If you do prepare a revision, and DON'T get funded this time, then you have a great chance to get funded next time and even if you get a job in the meantime, there will possibly be workarounds from both the department that hires you and your PO so that you can still benefit from the funding. Just watch the timing of accepting any offers so you don't render yourself ineligible to resubmit, and don't be shy about sharing your good score and its relationship to the projected payline in your job applications.

It is ALWAYS better to have a horse in the race than to not. Keeping your grant in play by working on that revision is always the best decision for your chances at funding.

Making the K99/R00 work long-term: what should be the focus?

Through my discussions on my K99/R00 forum, I'm noticing a trend for applicants: they get mixed messages and experience a lot of confusion about what the K99 phase of the K99/R00 is REALLY supposed to be about. Some Institutes allow the K99 phase to occur during the initiation of a tenure track position (i.e. you get the award as a postdoc but start an assistant prof job at the same time as your K99 phase starts). Other Institutes absolutely do not allow this, and require a minimum amount of time to be spent as a postdoc on the K99 portion, and then require transition to the R00 phase (rather than carry-over and continuation of the K99 phase through its maximum 2-year allowance).

Program's explanations for their positions vary: from understanding that people are in the sweet spot for K99/R00 and tenure track competitiveness within the same ~2-year window in their lives, to insisting that the point of the K99/R00 is to make people competitive (results/training-wise, not just reputation-wise, which a successful K99/R00 proposal makes you) for tenure track positions (as originally conceived) and that people who are already applying for TT should be ready to just apply for R01s instead. The latter aren't comfortable with the K99/R00 being *just* a rubber stamp "gold star" for TT application packages until after the awardee has played out their postdoc stage, and presumably think that postdocs should stay in their mentor's labs until they are fully cooked to some vaguely defined stage of additional "doneness." (which, it seems, K99 reviewers largely already expect...)

Unfortunately, that's just not how it works for most postdocs. By the time you're in prime K99 application stage, you're in year 2-3-4 of a postdoc position. You may or may not have a mentor who can afford to keep spending money on you establishing your own independent directions. You may be pressured to leave the lab soon, you may be pressured by your family concerns to move on from the low salary trainee stage. You are one of 200-300 applicants for any faculty position to which you apply. Like I said before, you cannot afford to put all of your eggs in the K99 basket, and might NEED to apply for jobs, yet should success in that process preclude you from funding if you get an outstanding score on a K99/R00 proposal and the reviewers think you would benefit from the training plan you described? (especially when that training plan can essentially just be transferred and still occur while you also start a TT position)

The other part that some POs might not quite have come to terms with (even though they are the very people with these numbers...) is that getting enough R01 support to get tenure is COMPLETELY non-trivial, even for highly successful beginning investigators with the New Investigator bonus. Here are my specific concerns about this:

1. The new structure and reviewing guidelines mean that you essentially have to have all of your preliminary data published. There simply is no room for preliminary data figures in a 12 page R01 format. If reviewers are going to adequately assess the potential for your project's success on an R01 scale (budgets typically the so-called 'modular' $250K DIRECT costs per year for 5 years), they need to see you have established significant feasibility for all of your aims, and these days that means peer-reviewed publication of preliminary work.

2. R01 budgets may be proposed at $250K for 5 years, but ALMOST ALWAYS get cut upon award by as much as 25-30% or MORE in amount, and as much as 1-2 years in time (so in reality you end up looking at a spending account that gives you only $150-200K per year for as little as 3 years). In other words, right back to R00 levels of funding. For many institutions, especially the fancy-pants medical school types, you also have to cover a large portion of your own salary and benefits (which is usually >100K), plus postdoctoral staff cost a lot more in places where the cost of living is high (as much as $100K/yr in salary and benefits themselves, think about what you all are wanting to ask for as your K99 salaries!). So right there, covering your own and ONE postdoc's salaries kills nearly the entire R01 budget at most institutions (and similarly, an R00 budget if you do come in with one).

3. Many, many many institutions (especially those aforementioned fancy-pants places and medical schools on the coasts etc.) are going to expect more than one R01 in a successful tenure package. And when you look at the numbers on the ground I described in #2 above, you can see why. In order to bring in the big papers in the Glamour Mags (which those big name places basically require for tenure), you are gonna need to populate your lab with more than just one postdoc and yourself. You are gonna need at least a couple of postdocs and a tech to keep things chugging at the pace that will get you there. In these tight funding days, that most likely means more than one major grant pre-tenure.

Of course not all institutions will require this of TT faculty. But nonetheless, the reality on the ground (with R01s being what they are and requiring what they require) is that a K99/R00 award can function as ~50-75% of an R01 as you get going pre-tenure. If used judiciously and efficiently, and if the training plan goals with appropriate mentoring are actually followed through, that can mean a substantial leg up on the tenure process.

My opinion: The goals of the programs should be to help facilitate long-term success in tenure track positions, not just to get people into them. The grant has been around long enough now that they should be able to start looking at their outcomes under different conditions (K99 phase long/short, what kind of job title held for K99 phase, what type of institution for K99 and for R00, future R01 success, future tenure success) and see how things are turning out. (NIGMS Director Berg anybody...?) My hunch is that providing more practical tenure track success mentoring (workshops? other mandated, direct contact programs? additional mentoring requirement BY grantees who successfully move on to R01 funding FOR early-stage grantees?) and allowing the K99 phase to be under the control of the investigator (rather than some imagined idealized situation) will better push future R01 and tenure success.

Namnezia cracks me up.

Recent lollzers from Namnezia:

Finally you are at a point where you are completely independent and a new adventure begins. But unlike being a postdoc or a graduate student in a well-funded, established lab with ample resources, starting your own lab is like becoming captain of a creaky old ship, partially sunk, with an inexperienced and somewhat dysfunctional crew and no compass. Ahoy! So while in principle you can sail in any direction you want most of your time is spent in keeping the ship afloat and the crew from killing each other.

(post here)

Repost: Culture gap: synthetic chemists and learning biology

Apologies for more reposting... I'm still trying to get out from the vacation backlog of life. New thoughts to come soon!

I started responding to this comment:

Now that you have invested so long to transform in to a ‘chemicalbiologist’, would you mind suggesting some quick tips from your journey for the people ho want to take the same path? Are there any books or some crash courses etc?

And got so in depth that I decided to make it a post of its own. So here are my thoughts about where to start to develop better flexibility as a synthetic chemist who wants to work on bilogical problems.

The best crash course I got was weekly lab meetings in a lively, rigorous yeast genetics/molecular biology/kinase signaling lab (one of my postdoc labs). I started out so clueless that I felt like I was on Mars for the first year and a half or so. But because the people in that lab were so open and helpful, and the PI is an engaged, active teacher, they helped me learn the “language” of biology-type ways of thinking and data/information representation.

It’s that language that you really need as a chemist moving into biology. And by “language,” I mean more than just terminology (although that is a big part of it). It’s also a change in visualization of information and getting better at logic puzzles. Imagine a multi-step synthesis with a blank at step 2, where 4-5 possibilities (which you have assumed based on either mechanism or other times people have done similar things) could fit in there to result in the product (or mixture thereof). In biology, you have to come up with ways to test *which* of those possibilities comes from the retrosynthetic direction (for which you are only postulating a route) and will result in the product(s).

In all of this you also have to accept that: a) your only measurement techniques are indirect, i.e. you usually can’t just analyze the structures with some direct spectroscopic technique and figure out what they are; and b) your assumptions might be wrong. So you have to do lots of control experiments where you also assume some certain set of reagents should DEFINITELY give the products, and some other set should DEFINITELY NOT. That gives you yet another indirect way to make you feel more comfortable with your assumptions. The hardest part for many chemists is having to be okay with indirect information. The second hardest part is having to remember that if your “result” gives you something analogous to “75% yield of the product,” you still have to think a lot about WHAT molecules/interactions are represented in that other 25%. You can’t just purify it away and pretend it didn’t exist.

Getting used to reading gel electrophoresis/Western blot (antibody detection) data, as well as biological “cartoon” format (where you mostly worry about conceptual connections, and not so much molecular mechanism and byproducts etc.), are some great ways to start. But you’ll probably need a coach to guide you through it and translate how the experiments work and what the results mean. Finding friendly, sharp biologists (whether faculty, postdoc or grad student–it doesn’t pay to be snobby about this, sometimes the trainees are gonna be WAY better at teaching you! Just make sure to credit them or repay them somehow!) can be the difference between this working vs. not working.