In talking to many grad students and postdocs I have found that quite a few find it difficult to prioritize experiments in their projects. Creating a tree of life of a project should help some, but still, the tree has many branches, and in principle one could start with any of them to get to the root. What I found to be a simple solution was to divide the project into “skeleton” and “meat”. The skeleton is the parts of the project that really answer the key question that the project is all about. Think of it this way – would the title of your paper change if the experiment came out one way or the other? If it would, this is your skeleton experiment and it is your top priority. Most good hypothesis-driven papers usually have a single figure that makes or breaks a paper – this is the skeleton figure. It typically shows that the hypothesis is correct in a bunch of different ways. The other figures contain additional controls, mechanistic insights, prove in vivo or disease significance etc. They are the meat of the paper. The skeleton will to a large extent put a cap on the perceived impact of a paper. A paper with unexciting skeleton will not be highly regarded no matter how much meat you throw at it. Conversely, an exciting skeleton makes an even bare-bones (pun intended) paper look interesting. So going back to the original issue of prioritizing what you will do next – make sure your skeleton is rock solid before you start surrounding it with meat. Otherwise, your project may crumble in front of your eyes after you’ve spent a ton of time and effort on it.