When you have a very expensive hammer... My favorite studies are those that aren't technologically fancy, but test a big idea. This is the study that I am most proud of to date. b_b and I just used luciferase assays for miRNA activity to demonstrate functional exchange of miRNAs between cells. The trick was that we expressed C. elegans miRNA in one population, and had a luciferase reporter for it in another. Super short and sweet, and nothing fancy involved.
It's hard for me too be too critical, given that my current project is somewhat of a hammer targeted at what I hope is a well-chosen nail. But I now have my sights focused on learning what other big-picture research views are out there. My undergrad institution had a lot of emphasis on structure. Some days I wondered why anyone would even care about that topic, but others it all clicked and I saw exactly how a particular system could be understood through the precise physical interactions of its part. But what other worlds exist within biology outside the current trends of massive sequencing, -omics, and advanced imaging?