Thanksgiving experiment

I'm gonna picture-blog this one, because it's just not the same telling this story without the images, and I am lazy about thinking and writing right now (too many proposals to write tomorrow! Need brain energy conserved!).

I know before I have talked about how being too wife-y (you know, stereotypes, baking, worries about perception that may just be me being paranoid) freaks me out sometimes. But the truth is, I *LOVE* being domesticated, I love cooking and baking, I think of it like planning large experiments and art projects, with multiple components that have to be coordinated and a lovely outcome where I get to show a little bit of my personality (unless I screw it up and it's gross, then it gets to be a funny story, but I'll brag that this doesn't happen very often). We hosted our family Thanksgiving at our house, and I got to wife-out completely all day, and it was awesome.

I work better with a plan (and so does my family, although they still spend the whole time going "What am I doing now? What about the potatoes? What is happening with the *insert name of dish here*?"), so I totally nerded out and formulated a set of protocols and a schedule detailing the phases of the day:

Close up on my "phases" schedule:

Having the schedule meant that everything got done on time and I didn't have to stress out.

The parts were prepped:

The pre-cooking got done:

everybody got to play Rock Band while the heritage Bourbon Red turkey cooked:

And we had a good old Midwestern, euro-tinged Thanksgiving dinner on our new wedding china (pretty much the only time we'll be using this stuff...right?):

I even flexed my artisan baking skillzz, making a pretty awesome chocolate cake (with ganache icing and pomegranate seeds), kind of just so I could use my cake stand, but also because my Scottish husband thinks pumpkin pie is disgusting:

Utterly confusing gremlin problems

So, it turns out that the problem that ruined my week is something much different than I thought it was, and maybe not the same kind of experiment-killing gremlins I thought at first.

See: we make peptides here, and the way you characterize peptides is by HPLC-mass spec. It tells you 1. how many components are in your crude material (hopefully less than 2!) and 2. the molecular weights (and thus identities) of those components. When you make your own peptides, you generally know which amino acids you added and in what order, and you also know what reagents you used that might have given strange byproducts.

The most common problems are a) deletions: missing an amino acid here and there for some % of your crude material; and b) terminations: chemical side reactions that stopped your peptide dead after some particular amino acid. Both of these give predictable products, so you can do fairly simple detective work to determine the source of a problem (made wrong concentration of solution, reagent was going bad, etc.). Thusly, uninterpretable LC/MS data, that gives you a mass or masses that have nothing to do with what you tried to make, is extraordinarily confusing because unless gremlins changed your amino acid solutions around, THERE IS NOTHING ELSE THAT IT COULD BE.

Our result had ONE peak in the UV trace from LC/MS--that pretty much means it's one compound (unless other components coelute, in which case they'd have to be pretty damn similar because our LC gets fantastic peak resolution)... and the mass spectra associated with that peak ARE COMPLETELY WEIRD. I have plumbed the depths of my knowledge of molecules, ions and fragmentations and have been completely and utterly stumped. I've also found that this strange behavior is exhibited by ONLY, but ALL, peptides with a certain sequence at their C-terminus, through a number of analogs I looked at. I also found that even my CONTROL peptide from my previous lab, which had NEVER looked like this before, is showing the same wacky thing. Given that this control peptide was stored lyophilized at -20 for the whole time, there is next to NO chance that it actually chemically degraded, and besides, the MALDI-MS (which only shows whole peptides in linear mode) is NOT showing the same thing, it looks fine there.

All of our other peptides that don't have this certain sequence are not showing this behavior, they look totally normal. So whatever I am seeing has something to do with this certain sequence, and my new-lab mass spec (which is a different brand than my old-lab one). I checked everything like the source voltages etc. and matched up as many of them as seem possible to match up to the settings on old-lab MS. Still no change in the spectra. SO WEIRD. There are only certain relatively predictable fragmentations one would expect here, and none of them explain my crazy ion series.

I ended up calling in the experts on this one, and so hopefully we'll get to the bottom of this crazy gas-phase ion chemistry mystery. I am at my wits end with trying to puzzle it out, and my poor lab staff is all new to peptides and mass spec so they are completely confused.

Actually, Science DOES think about these things.

I don't know much about this field, and of course there is no conclusive discussion (because there hasn't been one of ANY neurological issue so far in science and medicine--we're still working on figuring out how everything about neurochemistry systems work). BUT it is simply not true (as suggested by JLK in a comment about Ambivalent Academic's post in response to mine) that it's all a "myth" that women experience strange and disruptive neurological symptoms as a result of hormonal changes.

Unless there was some major debunking study that I just didn't happen to find in my Pubmed search for 'hormone levels pms,' it looks to me as if plenty of people are trying to understand this and clinicians take it pretty seriously.

I haven't read Fausto-Sterling's book so I cannot comment on what evidence she provided for her apparent assertion that "PMS does not exist." But if she thinks it doesn't, she must be as fucking lucky a lady as JLK, to never have experienced these feelings of someone else inhabiting her body dictating her response to the world around her. I'd like some of what she smokes, please.

On being a woman and a leader

I am certainly the one, and I know enough about myself to know that I am also the other despite the strange, intangible confusion that I sometimes feel as a result of the former. Today I'm going to write about biology--my own biology and biochemistry, how it goes on in my life and lab and which I study quite subjectively in myself without any good positive or negative controls, and without nearly enough systematic data (although I wish I could get it!).

See, all the fighting of the good fight, all the discussions about what rationally and objectively should be done as a leader and in difficult situations and when managing people and when running projects etc., all of it becomes like a jello tower of unsureitude at certain times when my hormones change who I am. And that really is what it feels like: you go from one week of being like a razor cutting through the bullshit and carving this amazingly solid beautiful map of what is happening now and where it needs to go... to suddenly overnight wondering how you ever managed to understand anything, seriously doubting the abilities of the people around you, your own abilities, and your ability to even assess other peoples' abilities. You, who are outgoing and friendly and comfortable with people (even difficult people), good at getting what you want and need, turn into an awkward, laugh-too-loud and make weird non-sequiter comments, detail-forgetting airhead, who comes down like a bolt of lightning on anyone who does something stupid. I feel all of this from inside, and some of it shows outside. It changes who I am.

I can't understand things, I can't make decisions, my confidence is gone, my anxiety is huge, my perceptions of people are obsessive and threatened and/or judgemental...

Or are they? Or is it just my own perception of myself that I am wrong? Is it that I can really see the truth and am not blinded by my usual feeling of wanting to be nice? I JUST CAN'T TELL. The worst is how you can't tell.

The scariest part is how I never even know where these waves of body-snatcherism come from until after the fact when the chemical cloud has shifted and my brain is not being overwhelmed by WHATEVER it is that causes this (is it a LACK of estrogen? An OVERABUNDANCE of progesterone? Or just the IMABALANCE or SHIFTING of the two and whatever other ones like prolactin or lutein that are all pummeling or not pummeling as usual or WTF is going on). Because of human biology, this thing that comes over me from these hormonal shifts really does change who I am, my fundamental brain chemistry that determines how I interact with my environment.

So what does this mean for me being a leader? I do, and I have to, fight my way through these things. I suppose other people probably just see them as a part of my personality, the natural range of behaviors I present, probably don't even really notice the difference--but it's so upsetting to feel from the inside that it's some other thing taking over making me somehow different from who I really am and who I want to be, for a significant portion of my life (~25%). And how do I trust myself to lead, and to make the right decisions and judge appropriately and productively from this kind of mindset? Isn't this the fundamental question we all try not to think about and don't know what to do about? Because I might be different and less fair when my hormones change me, and then how can I be trusted to be in charge?

I'm asking this devil's-advocate-facetiously, of course, but it's a real question, and so far the discussions on women as leaders try to set this up as a non-factor and push it out of the way, because it's a freaky problem--both unsolveable and non-understandable. What does it really mean? Does it mean we A) can't make the right judgements, or does it mean B) we have some extra-special supernatural-natural abilities to make even better judgements during the times of harsh no-bullshit critical feelings? It certainly adds another cosmic dimension to the difficulties of leadership, and science too since it gives me such a feeling of ineptitude and mental thickness.

I really don't know, and it is just so stressful to not know, and to find that no matter what you accomplish, how good you are at people, everything else: there will still be recurring, unavoidable days when you're a little kid again feeling like you just said something really dumb in front of the grownups (stupid), or threw a rock at the defenseless neighborhood weirdo out of spite (pointlessly mean) (and no, I never actually did that but that's what it feels like).

Whoa whoa whoa just a minute here...

Young Female Scientist clued me in to the discussion about Obama appointing Larry Summers as Treasury Secretary.

This is so disturbing to me! I used to work with Project Exploration, a non-profit promoting the involvement of inner city kids in science, particularly through Sisters for Science where I did after school presentations for girls and just generally hung out at retreats and such as an example of a woman in science. (More clues for those of you interested in who I am). The Obamas were strong supporters of the program, and I know at least Michelle attended one of the big fundraising events for PE over the last few years. They have smart, with-it young daughters, and I bet it would really piss them both off to know that this guy might think their daughters might just be inherently not smart enough to be whoever and whatever they want to be.

My little ducklings

I have such a strong mother hen instinct--its hard for me to let go and just let the people in my lab get on with things. But I've been trying very hard this week to just give my rotation students and new post-doc the basic instructions, point them at the manuals, and say "Go for it and come find me when you get stuck." So far, it's working well: they are all coming along much more quickly and showing me their capacity for figuring things out and independent learning. This benefits all of us: they learn more and learn faster when they have to figure things out, and the sooner I feel confident and comfortable with their initiative, the sooner I push them to be more productive, and the sooner I let them do the cool stuff.

Of course, not everyone can be managed this way: some people need much more hands-on, direct training and interaction, and really need their every move to be monitored. That seems to correlate strongly with visual memory skills: the ones with bad memories can't remember what they did when and why, and consequently need way more controlled, involved management to be successful (SOMEBODY'S got to know what the heck is going on, and if they don't, it has to be me). I wish everyone could have the sharpitude that (of course) *I* have, but sadly they just can't.

It's hard to decide where you draw the line (for their continued employment) when someone can't function independently in a complex context, and I guess that's part of what makes for different roles in a lab. It's an essential characteristic of a Ph.D., but not so common among the non-PhD wanting/getting/having crowd, so my expectations have had to change. At previous institution, all of our technicians had that special 'excellent grad student' quality (which is why many of them didn't stay with us long...) and so I guess I got spoiled. But at new institution, not everyone in support roles is quite as independent. That's okay, I can work with that--it just takes more time to get used to, and makes me unsure of how high is reasonable to set the bar.

K99/R00 awards and the NIH New Innovator Award-UPDATED

So, I was exploring the options for the New Innovator Award pre-application, and saw the following text in the 'Eligibility' section that gave me some concern:

"PDs/PIs must meet the definition of β€œnew investigator.”... Current or past recipients of K awards are eligible except for the following: K99/R00 or other Independent Scientist and other non-mentored career awards (K02, K04, K05, K24, and K26)."

This concerned me a lot, because while they said we'll still be considered 'new investigators,' one of the the things I have been worried about is that this won't really turn out to be the case, and the K99/R00 might be secretly/under-the-table causing us to be considered 'well-funded' in that against-the-rules kind of way. This seemed like an affirmation of that potential shift in attitude about it, and that worried me.

BUT it turns out that after more discussion, they at NIH decided that they had gone the wrong way on that issue. I emailed the program director of the New Innovator award, and got a really reassuring response: they changed their minds on that and they will be updating the PA soon. So apply away this Dec/Jan, Kangarooers!

UPDATE: It's official!

BTW: There are finally some metrics showing up on these awards, some discussion here. They also totally stole some of my assertions about how good a K99/R00 application can be for you even if you don't get it! πŸ˜› Heh.

Data data data!

We have some really cool-looking preliminary microscopy data from the work that one of my students is doing right now. It's looking like we CAN use one of my ideas for something I tried in my post-doc and only got half-ass started. It's still in the 'fuzzy picture, kinda sorta starting to tell us something' stage, but the controls are helping us get more confident that what we are seeing is really there. I'm not going to tell you what it is, but I'll show you a sneak preview picture of our slightly better looking version:

Like I said, still kinda fuzzy and have a lot of background, plus the objective isn't ideal for what we are hoping to show. But it represents a very cool new direction for me, and the independent demonstration of the student's ability to get some shit done and learn some new techniques, so it makes me happy!