Monday, December 23, 2019

Synapse proteomics (and phosphoproteomics) and sleep cycle!

...and the winner for some of the prettiest and most useful plots I've seen this year goes to two recent (new?) studies in Science about proteomics of mouse synapses and sleep.

(One and two)

I stared at the very top for several minutes in the afternoon when my brain is generally working at it's typical extremely limited capacity before I realized it's changing signals over clocks!

Here is my summary:

1) Sleep is super important at a proteome -- and particularly a phosphoproteome level (there are really cool analyses of neuropeptide signaling events here as well. (Scary for people with intense insomnia? Maybe?)

2) This may be completely untied from the transcriptomic regulation which is totally circadian-ish. (This is kinda big, right?) I'm always ranting about how low the correlation is between transcript abundance and protein abundance and here is a CRITICAL system where the two appear completely untied from a regulatory standpoint!! Killer paper

3) When you're starting out with a tiny amount of material (I'm doing synapse work right now and, we'll of course, model it after this paper) and you have to do phosphoproteomics on it -- that's when you call in Cox Lab for help.

4) One thing that stands out a little here from how we go about it is that we start with distinct brain subsections that are surgically removed and then the synapses are enriched from, for example, the hippocampus first and the pre-frontal cortex, because from the RNA-Seq stuff we're very concerned about mudding signals. Here they appear to have started with a big section of the brain and concentrated the synapses from them at once. Considering our maximum extraction from the hippocampus synpases is like ~1ug...maybe...this is likely critical to get phosphopeptides.

5) We're completely stealing the layout of this paper for our synapse studies. 100% just copying how this is laid out and putting our data in it. Worked for them. Two (2!!) science papers?  Totally deserved because this work is killer.

6) Many people will still read this and then try to do transcriptomics of the brain, look up what proteins those transcripts make and will call it "quantitative proteomics" because...well....

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