Wednesday, February 24, 2010

Rest of the recap

So without going into too much scientific jargon, the recap of the actual meeting is pretty sparse. My committee met without me for a bit, which is the protocol. No idea what they talked about. I started my presentation by overviewing the model and specific aims again, but I didn't do (or need to do) much more background than that.

I went over some of the general measures (animal weights, heart weights, scars, etc) which involved a little discussion. The debate has always been that sometime the high fat diet makes the rats heavier, and some times it doesn't. They never become obese, which would be another confounding issue in the research, but it's something we always have to discuss.

I spent a little time on echocardiography but tried not to focus on it too much since we have much finer measurements that we take at terminal surgery. I did spend some time on those measurements. The biggest comment was from Dr. B, who argued that we don't see the systemic signs of heart failure in these rats that you would see in people. That's a model issue--rodents don't get anasarca, and the failure is more moderate (even with an LV scar that would kill patients). We're consistent with other models, and my boss just put out a paper looking at more of the adrenergic state of our animals, so I tried to defer to that paper a bit.

That line of questioning was my first indication that Dr. B would be the primary cross examiner today, as usual. Sure enough, once I moved into the insulin resistance data, he let loose. He doesn't like how we measure peripheral insulin resistance, even though we: 1) measure it in multiple ways, 2) report the measures most commonly cited/published, and 3) have the director of the mouse metabolic phenotyping core, who oversees these experiments, sitting on my commitee.  We debated for a bit about other measures Dr. B wanted to see, but everyone else was happy with the report, so we moved on.

The next section was the PET data, which Dr. B is big into right now. Everyone was happy with the images and the final analysis, especially with how clear cut the results were. Dr. B argued about how this result could be an artifact of our glucose infusion protocol, but I pointed out the controls we did to make sure that wasn't the case. If anything, I was polite but a bit over-defensive. I wasn't about to redo all the (very expensive) experiments to tweak one little thing so he would be happy. It wasn't nasty, but once again, Dr. B was interrogating and I was left to defend myself.

We then went on to the protein signaling work I've been doing. This is what my committee was really on me for last time: show a mechanism. They wanted to see signaling changes. So, I've been working for the last six months to show signaling changes. This has involved a lot of troubleshooting, which I didn't get into at my meeting, but it has been very time consuming.

And of course, this is when Dr. B said none of the signaling mattered. He said that showing intracellular mechanism didn't show us anything additional about the model beyond what we saw from the PET data. I actually had to defend the search for signaling changes even though last time, he was the one that wanted me to do it.

After some protein discussion, we got to the experiment that didn't work in Utah. I think it would really complete the story--it is the final common pathway of the signals we are studying--but it is technically difficult. This is where the rest of my committee showed their first signs of concern. The consensus at the time was that yes, we needed this data to have a complete story. They suggested that I spend a few weeks troubleshooting, but if I couldn't get the method to work on the frozen tissue I had, I'd have to collect new fresh tissue. This would involve at least 32 more animals, which would take minimally a month or two to collect. The committee's suggestion was to tinker for a month and then have another meeting to see how it went.

I also went over my timeline for return to med school. I said that I am slated to start my clerkships the day after Labor Day. My committee asked what my drop dead last date was, and I said November (that still puts me in residency in 2012--anything later pushes me back a year). They were concerned that I might run out of time if these new experiments didn't work.

And then I presented my outline for uniting my two publications into a thesis. This is actually where I anticipated the most debate. I was leaving out all three years of work that I did in Dr. B's lab. One, it was never published. Two, we never got to the heart of the issue. Three, the heart of the issue wasn't that interesting. Four, it has absolutely nothing to do with either of the other two labs I've been in.

I thought Dr. B would raise a stink about that, and I figured G would probably agree with him. As I mentioned in the last post, everyone was on board with my idea--everyone. They liked the overarching theme, and although they agreed it would take a lot of writing to link the two, they thought it was a good plan.

So then I left again, they discussed for a while, and I came back in.  According to my boss, when she was with them but I was gone, they were still saying that this difficult assay was really key to getting the paper published.  When I came back in and my boss left, they were saying that the experiment was important, but the data I had really could stand alone by itself. They had concern about the particular difficulties associated with the assay, but they were all pleased with my progress.

After the meeting was over, my boss and I chatted about what had been said. We both agreed that maybe instead of prioritizing this tough experiment, we should tie up some loose ends, write the paper, and submit it. We figured it wouldn't get accepted right away, and that would give us time to tinker with the tough experiment while we were waiting for comments.

As I mentioned in the last post, then Dr. B and I chatted, and he said that he and G had discussed the same thing.  My boss then had a faculty lunch with two of my other committee members, and they said they were on board.

So the plan went from me trying to get this tough assay to work before sending out the paper, thus putting me in a time crunch, to having me finish up some loose ends, writing, and submitting the paper before I start troubleshooting the hard experiment.  Weird how things changed dramatically in an hour.

There wasn't a lot of hostility in the meeting--just the typical interrogation by Dr. B. It's strange though--he used to do the same thing when I was in his lab. We'd go over my talk before my meeting, and he'd be on board. Then he'd rip me apart in the meeting. And then he'd be all positive about it after the meeting.  I just don't get it.

I'm still a little stunned at how things went down, but the long and the short of it is that I'm now on the path to graduation. As is typical with scientific time (read: glacially slow), it'll still be a few months. It'll be about a month or so to finish experiments and write the paper. Then we have to submit. Then it'll be maternity leave probably, although I am hoping to at least start the tough experiment before I go. Then it'll be writing the thesis, doing experiments/revisions for the paper, and defending. Still late summer, by the time things are done.

Totally crazy.  Maybe this will sink in by tomorrow. I'm actually going to graduate!

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