The latest version of the query was on the Twotts:
My advice, of course, is to do both of these things. Start up a new line of attack right away as well as do a good job with the line of work that your R00 is for, with the thought of converting that into an R01 project later.
Before anyone gets to that they need to sit themselves down for a little pondering.
This advice that I give (go big right from the start) has to be modulated by two critical factors. What kind of scientist you want to be and what kind of scientist you are expected to be.
So, first question that you need to ask yourself is what you see as your ideal lab operation both right now (next 2 yrs) and into the future (say, year 10). What do you prefer? What is going to make you happy both scientifically and mental-health wise? How much can you handle? How much can you handle five years from now (because, dear n00b PI, what seems overwhelming in year 2 is much easier in year 4 or 8)?
This has to be your starting point. If you can't see your way to a sustainable, desired future operation of your little cottage industry of science......well you aren't going to be happy. What do you want to do? This is critical for deciding how to go about attaining your goal and for deciding what strategy to pursue right now.
The second question has to do with what you are supposed to be doing given your job category, University type, subfield, etc. Are you expected to be a two-grant lab? Are the sorts of production rates that are expected of you only possible with more support than one R00 can provide? Look around you. What are your peers in your Department, in your School of X and in your subfield doing?
Do you have a huge teaching burden? Do you get a lot of free undergraduate labor for your sciencing or do you need to be able to hire technicians and postdocs?
There was a followup...
Which implies that local advice was to focus on the one project, then ask for more money later.
Danger, Will Robinson.
This could be the answer to the local expectations question. Could be. But it could also be the voice of long outdated, or generationally privileged, experiences talking.
Older colleagues may think you young pups are in the same era that they enjoyed. An era when the expectations of renewing a funded project (that was reasonably productive) were very high. Those expectations are not high anymore. It is career suicide, imnsho, to assume that you can submit a new application in the final year of your current single-grant support and get refunded immediately. Suicide, that is, assuming that you are in a place which demands essentially continual funding. Now, of course, if all the people around you have gaps in funding all the time, and it never seems to perturb tenure chances, then this changes the equation for your individual situation.
R00-holders, and those who have managed to acquire major funding in the first 1-2 years, face another strategic consideration. A little bit ago, someone was proposing a "twins" strategy of simultaneous submission so as to game the ESI designation. It's worth a read. There is another consideration for the first couple of years of appointment. The study section sympathy for lack of independent productivity (read, papers) from your own lab diminishes quickly with time. In year 1-2, the sane reviewers are not going to expect that you have generated substantial amounts of data or published papers "from your new lab" yet. They will review you accordingly. Once you start into year 4? Well, you will be hard pressed to find any reviewers being sympathetic. So this gives you a sort of grace period to send up grant proposals with very minimal supporting data and without a Biosketch filled with your senior-author pubs.
So, as always, you need to do your career research and some hard introspecting about your plans. Nobody can hand you the answer. You need to collect relevant evidence, determine what is the best path forward for you given your situation and select the best course of action.
Kind of like doing the science itself.