What is your dirty little secret?

Let's be honest, no "novel" technology is perfect, unless your name is Gutenburg. And last time I looked it wasn't. So if you, like me, make technology for a living, I want you to confess, as Dwight Bergles would say: "What's your dirty little secret?" I was looking at the special issue of Brain Cell Biology on optical techniques and saw, much to my surprise, that optogenetics is not perfect after all.

Many of you will know that there has been a very Big Splash made with these light-controlled ion channels/pumps (see entry for 1st may 2007). What we now get to find out is that one half of yin-yang partnership ain't so great after all. It turns out most of the chloride pump (NpHR) never gets to the membrane in vivo, but gets caught up in the ER (see pic above, Fig. 3A from BCB (2008) 36:129-139). On the left, you see what happens to NpHR in a mouse, most of the protein gets stuck in the ER, often as huge blebs. With much tweeking, Deissseroth and co-workers have removed the blebbing, and improved the current/photon by up to 80%. Still relatively little protein ends up in the dendritic plasma membrane (right panels, eNpHR).

So, come on, confess, what's your dirty little secret?