Heyo -- thanks for the heads-up on Twitter. I'm the sysadmin at a small university department, and I work with scientsts studying gene expression. They're good and patient people, but sometimes I feel a bit like I'm questioning the foundations of their work...which feels either rude or ignorant.
First off, I'd always been under the impression that DNA was only/mainly used during reproduction -- a cell divides under DNA direction, some bit of the cell is the machinery that makes whatever protein is needed during its life, and DNA isn't involved much after that. However, I'm starting to understand (I think...) that I've got it all wrong. My understanding now that gene expression can basically turn on a dime, and that *this* is the usual way a cell makes a protein: something happens to a cell, it says "Whoah, I need protein X", and it starts transcribing the DNA so it can manufacture it (modulo things like gene regulation). This process can take very little time (hours or less). Have I got that right?
Second: one of the things they study is datasets of gene expression in post-mortem brains. (Well, technically I guess I've got that wrong, since genes aren't expressed post-mortem... :-) As I understand it, someone dies -- say, someone with schizophrenia -- their brains are donated to science, and at some point someone does microarray sequencing of blendered neurons. This is compared to brains of control subjects, gene X is found to be over/under-expressed in schizophrenic brains, and so gene X is involved somehow in schizophrenia. (This is a gross simplification, especially in the case of schizophrenia; my understanding is that these signatures cover many, many genes, they're subtle at best, and there's nothing like "a gene for schizophrenia".)
What I don't understand:
a) Since time passes between death and sequencing, how much fidelity does/can this have do what was going on at the point of death?
b) Even if it is a good indication of what was going on at death, how does that relate to a long-term illness like schizophrenia when (assuming I've got this bit right) gene expression can turn on and off in a very short time? I realize there are (ahem) ethical problems with doing brain biopsies on living subjects, and that post-mortem is the best that can be done -- but how good can it be?
Many, many thanks for your time. Any questions about system administration, let me know. :-)