Question: what experiments are you conducting to learn about cell suicide?

Mariam Orme answered on 13 Jun 2010:

Well, I’m trying to understand more about the molecules that control the cell death program. When the program is triggered, molecules called ‘caspases’ become activated, and they chew up other molecules to dismantle the cell in a controlled way. It’s very important that caspases are regulated properly: if they became active inappropriately, cells would keep dying and your body would turn to mush, but at the same time there needs to be a mechanism to activate caspases quickly and efficiently to get rid of damaged cells, for example to stop tumours from forming. We don’t understand very much about how caspases are regulated, so I’m trying to find out more.

I discovered that a molecule called ‘crinkled’ interacts with one of the caspases, and so now I’m trying to understand what crinkled does: is it important for activating caspases, or perhaps for keeping caspases turned off in normal, healthy cells? Or maybe it has nothing to do with cell death at all!

These are a couple of the key experiments I’m doing to try and understand this better:

– What happens if I do some genetic tricks to get rid of the crinkled molecule?
If crinkled is needed for cell death to happen, then if it’s not there anymore, cell death shouldn’t be able to occur.
Or if crinkled is needed for restraining caspases in healthy cells, then if crinkled isn’t there anymore cells should spontaneously die.

– If I do some different genetic tricks to put more crinkled into cells, what happens?
If crinkled’s job is to make caspases active, then having lots of crinkled around might activate caspases when they would normally be ‘off’.
But if crinkled stops caspases from becoming active, then having more of it around might mean that caspases can’t be activated any more.

My initial experiments are suggesting that crinkled helps to make caspases active, because at least in some situations, when I take it away cells don’t die as efficiently as normal. But I still need to do a lot more work to understand exactly what crinkled is doing!