Sometimes in the life sciences, it’s really tempting to look at a process like mitosis and think, “Wow, we really understand that,” and stop asking questions. In other cases, significant barriers like reliable expression of a non-endogenous reporter in an organ such as the brain is a challenge that seems impossible to overcome. However, those are precisely the moments when science and scientists need to push the boundaries of what we can see. In this post, I discuss two studies where researchers are literally seeing what could not be seen before by developing new methods for looking at their model systems.

In both papers discussed here, the HaloTag® protein and ligands were key to developing new methods allowing scientists to visualize biological phenomena that had been previously inaccessible. HaloTag® protein allows different functionalities to be linked onto a single genetic construct, rapidly and covalently under physiological conditions for experiments ranging from live-cell imaging to capture of protein interaction complexes (1). In the first study, HaloTag-CENP-A + JF635 ligand was the specific tool that let them directly see, in real time, that chromosome-attached microtubules pivot as the spindle elongates. In the second study, HaloTag was used to create a protocol for PET imaging of reporter gene systems in the brain.