The quasispecies nature of RNA virus infection and the role of sequence change in the evasion of the humoral immune response!
I reckon one word in 4 of that statement makes sense to most people.
We worked out in the 1990s that most of the changes we can detect in HIV (and subsequently in HCV) are not just random rubbish. Many of them can be shown to change the virus so it can continue to grow even though the immune system has worked out how to kill it.
This constant change is like a giant box of false moustaches which the virus uses to get past the body’s security system (I’ve just made that analogy up, I really like it!).
I think my biggest discovery actually doesn’t come from the project I’m currently working on – I haven’t been doing this for long enough! But this is something I did when I was working as an intern in Caltech, California:
We know there is one gene, called miR-125b, that gets over-expressed in a type of leukaemia, meaning that the cell pays more attention to the instructions in that gene than the ones in the rest of your DNA. This gene is a micro-RNA gene, and its job is to control how much of each protein your cell makes – it only has an effect on RNA and proteins, and shouldn’t affect DNA at all. But in my experiments I found that the leukaemia cells that over-express miR-125b get a part of their DNA completely deleted! We have no idea how this happens, but we do know that getting rid of that bit of DNA makes it a lot easier for the cancer to grow. So we’ve discovered a new effect of the miR-125b gene in leukaemia, and something new to look out for when we’re trying to make a cure.