Wednesday, April 23, 2008

Ending a Statement With a Question Mark?

Have you ever conciliated your way through a scientific discussions by ending negative statements or disagreements with an implied question mark? I do it a lot, and I'm not sure I like the reason why.

As a woman (and maybe as a man too, though I have not had direct personal experience with this, any insight would be welcome), I tend to walk the fine line between directness and conciliation. I am naturally emphatic, and used to state my opinions strongly-maybe too strongly-carried along by the force of my convictions and the absolute determination not to give in to anybody. Some of this crazy certainty faded with age and some wisdom, but I still am pretty definite in what I believe and inclined to be forceful in what I say.

One big reason why I stopped being loud and emphatic and thumping my metaphorical fist on the table is because I realized I hated being at the receiving end of such treatment. I hate being steamrollered, its uncomfortable and puts me off the discussion. I also found that not thumping table meant I could hear other people, a nice change. So politeness and a genuine curiosity to hear other people's thoughts started me off on my path of less declaiming and more questioning. As an added bonus, people warm to gentle conciliation more than they do to vocal steamrollers.

That there is the rub: within the reasonable demands of courtesy, how much should one conciliate? It's a reflex now, I always take the diplomatic path rather than just say what I think outright. I like to think that I stand by my convictions-I'm just more mellow about them-but is that really true? Have I gone too far down the road of conciliation? In lab meeting particularly, or during seminars, I ask questions and challenge people almost apologetically. In some cases, it makes the questioned feel more comfortable, and in some cases it makes them more dismissive of your question. Is a reputation for being thoughtful and a disinclination to put people on the spot worth being dismissed?

Why so I have this need to instinctively subdue my challenges? The saddest thing is that I think I do it because I am a woman. There are men in my group who are distinctly less indirect, often outright rude and in-your-face with their challenges and it doesn't affect the esteem in which they are held. And in the most bitter of stereotypes, when other women do the same they are called aggressive, bitchy and unpleasant. I used to be against overt feminism because I thought it was loud, exclusionary and exhaustingly unproductive, not to mention bound to get you laughed at. It galls me though that the natural instinct of intelligent ambitious women of my generation is to tone it down, to try and not become one of those women who became PIs in the 1970s and -80s. While I am certainly not a fan of rudeness or putting someone else down out of a sense of your own superiority, I am so tired and fed up of ending every sentence with an implied question mark.

This post is my 50th on this blog(I'm slow), and its also for my mother, the kind of feminist I would like to be.

Tuesday, April 15, 2008

A Link Between Environemental Toxins and Autoimmunity?

The title of a paper in the advanced online publication section of Nature refers to a possible link between environmental toxins and autoimmune disease: an irresistible hook, and of course I could not resist. So followed some excited perusal of Veldhoen et al (doi:10.1038/nature06881) and another paper on the same subject, Quintana et al (doi:10.1038/nature06880), also in the AOP section.

So is there a link between environmental toxins and autoimmunity? Well, maybe, though I am not entirely convinced of that aspect of things, and here is why. Both papers discuss the effect of triggering the aryl hydrocarbon receptor (AHR) on T cells (description in the sidebar, for those of you are interested). The AHR, to my chemistry-ignorant mind, is a protein that binds hydrocarbon molecules with aromatic rings. The AHR is a type of protein, called a transcription factor, that decides when genes are turned on. In tune with this known ability of the AHR, both studies find that triggering the AHR on a subset of T cells called helper T cells turns on genes that influence the function of these T cells.

Helper T cells can direct the immune response along different paths, towards a more allergic response, one that is better suited to the fighting of infection, or towards a more inflammatory response which can result in the immune system attacking oneself—“auto”immunity. Helper T cells work by producing cytokines, small proteins that zip around the body carrying messages from one cell to another. Helper T cells that produce the cytokine IL-17, called Th17 cells, play a large role in autoimmune diseases: for instance, blocking IL-17 in a mouse model of multiple sclerosis, experimental autoimmune encephalitis (EAE), protects mice from getting the disease. Other helper T cells—regulatory T cells or Tregs—combat autoimmunity by battening down active T cells, and giving mice Tregs can protect them from a variety of autoimmune diseases. So helper T cells can go either way, either promoting or suppressing autoimmune disease.

Veldhoen et al find that triggering the AHR on helper T cells through its ligand FICZ* enhances the generation of both mouse and human Th17 cells. Treating mice with FICZ also accelerates the progress of EAE, suggesting that triggering the AHR enhances autoimmunity. FICZ is generated by UV treatment of tryptophan, an essential amino acid, and the authors suggest that it may be generated by exposure of the skin to UV light, thereby connecting environmental factors to an autoimmune disease. A connection I find a bit tenuous, but the idea is interesting and novel, and I am very curious to know what they find next.

Quintana et al present a more detailed study, with results that suggest something different. They find that triggering the AHR through a more famous ligand, TCDD**, leads to the enhanced development of Tregs, the tranquilizers of the immune response. Now, TCDD is thought to be very toxic, and is found in the environment (most infamously, in Agent Orange), but it seems to actually counteract autoimmunity, because treating mice with TCDD considerably slows down their development of EAE. Qunitana et al also agree that FICZ treatment enhances the generation of Th17 cells, and simultaneously retards Treg formation.

Both compounds bind to the AHR with different affinities, and possibly in different ways, which might explain their opposing actions. In any case, aromatic hydrocarbons are capable of modulating the immune response and shaping its eventual outcome, an exciting and novel set of findings. That they have such strong effects (reversing or accelerating EAE is pretty strong) certainly suggests that they bear further study, and back up the idea that things in the environment can have an effect on our immune systems. After all, having too many Tregs because you were exposed to TCDD may save you form some autoimmunity, but too-tranquil T cells are not very good at fighting off infections. Similarly, too much sun can turn tryptophan—which we absolutely need—into FICZ, which can then diffuse off into our bodies and do something to exacerbate autoimmunity somewhere. Food for thought.

*6-Formylindolo[3,2-b]carbazole (FICZ)
**2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin)

The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins
Marc Veldhoen, Keiji Hirota, Astrid M. Westendorf, Jan Buer, Laure Dumoutier, Jean-Christophe Renauld & Brigitta Stockinger

Control of Treg and TH17 cell differentiation by the aryl hydrocarbon receptor
Francisco J. Quintana, Alexandre S. Basso, Antonio H. Iglesias, Thomas Korn, Mauricio F. Farez, Estelle Bettelli, Mario Caccamo, Mohamed Oukka & Howard L. Weiner

Saturday, April 12, 2008

Multi-tasking Madness

"I hate running PCRs to type mice, because I could have been doing X experiment instead."

No I could not have done X experiment instead. I have two hands and one head and unless I can master the usage of my toes, its one thing at a time. The typing of mice (or testing of serum for tissue culture, restocking of boxes, running of FACS samples) is as essential as anything else, despite being boring as hell. This feeling of "I could have been doing something else, obviously more useful or constructive" is a fallacy, and a stressful one at that.

I feel such a strong impulse to multi-task all the time, but often its the multi-tasking that slows me down. I am naturally a quick mover and I tend to dart around doing things, keeping myself busy. This tendency goes to the extreme in lab, where I don't feel occupied unless I have three threads running. And guess what? I make mistakes and have to repeat things, which adds to my not-inconsiderable work load (I have a particular PCR jinx).

There is this drive today to get things done, faster and better, now instead of soon. Lab work is easier and research is more competitive, so it's easy to see how this has come about. Is it constructive though? If something takes a certain amount of time to do, what is the point of rushing it or wishing it along faster? Or, inserting other tasks into the gaps? One does get more done eventually, but at more cost to oneself. And is that really efficient in the end?

I have discovered that I do not like operating at full stretch all the time. Sometimes I really enjoy it, I am in the zone and buzzing. But the rest of the time, I think my research would be better served by my working with more discipline. Unfortunately, when one can work in the zone, one starts to expect it of oneself always, and that is just not realistic. So I am going to run PCRs and DNA gels, and only those, this Saturday and look out of my window at the sunny trees.

(I might reshuffle my papers, read a few, trackback a few references, no matter.)
(And yes, its Saturday, I know)

Thursday, April 3, 2008

Postdoc as Domestic Goddess (or God)

Skill 1: Combines ingredients with precision, follows instructions to the letter, but adds the occasional touch of improvisational flair with interesting outcomes. Occasionally works with the reagents at hand instead of what may be ideal, with perfectly acceptable results. Not afraid to use alcohol as necessary.

Skill 2: At the end of a process, puts everything away in its allotted space, wipes down all work surfaces, neatly collects trash. Surveys area, spots missed spots with the eagle eye trained by years of experience. Has no patience with others' sloppy work areas, is disgusted by ill-maintained and unclean surfaces. Is zealous about the weekly wipedown. Again alcohol accompanies as needed.

Skill 3: Monitors the health, diet and breeding habits of several small dependent creatures. Always has a mental map of which little creature is where.

Skill 4: Plans menus and processes days ahead. Has activities allotted to each day, to be carried out according to a strict schedule. Adheres to said schedule with admirable focus.

Skill 5: Does the shopping for supplies as needed. Prefers to do so on a regular schedule (schedule is important), but is willing to pop down to the shop when running short. Combines trips to shop with transport of laundry.

An alternative career maps itself out...

Wednesday, April 2, 2008

Blog List

Oh I am so stoked by this new feature on blogger (Draft blogger for now), it imports blogs from my google reader and posts them in my blog list! That is so good because I could not figure out blogroll and have been feeling bad about being a lazy one who hasn't manually entered everyone yet.
Love it. Because you are all awesome bloggers, and I am so glad to have found you.

Tuesday, April 1, 2008

Paranoia and the Destruction of the Soul

I wanted to write a happy post today since I'm in a really good life-mood (research mood is low-level fatalistic tending towards zen acceptance), but I've been thinking about paranoia a lot lately. A good friend and colleague is having a really hard time in lab because they feel like slices of their project are being given away without their consent. And they are right, the project is hard to partition in the first place, and there are three bright, invested individuals working on it at the same time. However my friend has made particular innovations, and is uniquely qualified to do some things, that they had suggested in the first place. This slicing and dicing has been going on for nearly two years now.

Enter full blown, pull out all the stops paranoia. Behaviour-altering, mind-bending paranoia. I won't share reagents, I'll never discuss a good idea in lab again paranoia. It's getting to the point where they are saying and doing things I don't think are characteristic or believable, and they are morphing into human jelly. And I just want to stand up and scream at them to stop it. I have tried to bring up the subject more gently and constructively than that, but an unavoidable side-effect of paranoia is that one perceives judgment and betrayal in what everyone says. So what do I do?

I think paranoia is the single most destructive emotion one can give in to. I know this regarding emotion from deep personal experiences; and regarding work from having been scooped three times in grad school. I have worked with many brilliant and paranoid people, and the one thing that always leaps out at me is the amount of energy they waste in spinning their paranoid wheels. It is such a waste of all that brilliance, all those (rapidly diminishing) neurons firing salvos of negative emotion. It drains you, makes you bitter, changes you in fundamental ways, alters your equation with everyone you work with, and is utterly pointless in the end.

It is both insulting and patronizing to tell someone they are being paranoid when they feel, legitimately or otherwise, that they are being deprived of what is rightfully theirs. However protecting one's territory can go too far, and when that line is crossed, it really messes things up. Academic research as it is today relies on the goodwill and respect of one's peers, and paranoia and its close companion suspicion, are the surest way to erode all goodwill and respect that anyone has for you. And in the end, it destroys your own self-respect, and no paper is worth that.

Saturday, March 29, 2008

The Endgame

I've been thinking about "the endgame" a lot these days.
(Style note: I swear not to begin anymore posts with "I've been thinking about..." anymore, it might be time for "It was a dark and stormy night...")

What is my endgame? With this postdoc and all that I am doing now, involving low-level politicking, writing etc. Let's say its an academic position in India, doing cutting edge research in infectious diseases. What then am I doing to go there? How specifically do I go about getting there, as opposed to just trying to do good research and sending up prayers to the gods of funding and publishing?

This is a novel way of thinking for me, and one that I think should have started a long time ago. I drifted into science because I was bright and academically-inclined. The drift wasn't aimless, it was influenced by the fact that I love talking to intelligent people about intelligent things, my mother is a scientist, and I thought science and scientists were so cool. I came to the US because it was kind of the done thing at my (competitive) college: my friends all wrote the GRE and sent out applications. Most of us did well, and nearly all of us went to good schools. I floated into biology because I liked both biology and chemistry, and biology incorporated elements of chemistry. I went where I did for grad school because they offered me a place, and it seemed really cool.

I don't mean to say that I just faffed through life and things happened to me. I think it was more that I hadn't found all the the dislikes and loves that I have now. I liked most things, I was interested in studying most things, and I looked on travelling as an adventure. I had no conception of the mind-bending cultural changes I was about to face, and I did not think for one second about how hard it would be to consider living and working in India after nearly ten years as an American scientist. I am pretty fortunate that things have turned out well, and I am very fortunate to have discovered both ambition and immunology. Fulfilling that ambition would be much easier if I had actually started thinking about my life and career choices more actively a long time ago. I didn't, though, and whether that was a function of culture, personality, upbringing, I can't say with certainty. But it is what it is, and I'm going to find out, soon enough.

Now I know better, its all about the endgame. Which includes immunology, India, a family, my large and extended family, writing, travelling and a faculty position.

Too ambitious?

Thursday, March 13, 2008

One Week at a Time

So my last post was about how charged up I am about an academic career.
With that in mind, let me describe my week:

Saturday: Transfected cells, let's say A cells, to use for experiments. Fed them, put them away, felt very good about the adventurousness of the experiment being undertaken.

Sunday: Realized while 40 miles away that I had completely forgotten to get another set of cells, call them B cells, ready for the experiment. B cells are needed for the final step of the experiment. Crap. Bummer. Well will just have to get them ready on Monday.

Monday: Got B cells, and third and final type of cells, called C, ready. A cells, of course are nice and confluent and ready to use, only I am not going to use them. F*cking A. Efficiently set up more of A cells to start the whole things again, but nested so I don't waste any time.

Tuesday: Set it all up, A cells, B cells and C cells. They are happy in the incubator, ready for me to read them tomorrow. Whew, that didn't work out too badly did it?
Transfected second batch of A cells.

Wednesday: Started off readings, all negative. Completely, and it doesn't even look like A cells make the protein I transfected into them (which is the whole entire point of transfection!). Double sh*t. No f*ck it, triple sh*t. Then the blinding realization dawns that I threw away my leftover B cells after using them yesterday, and I don't have any more going. There are no words, only anti-endorphins.

Thursday: Started round 2, with some alternative B cells. Also, smartly decided to check whether transfecting served any purpose this time, since I screwed up the previous time and let A cells go much longer than they should have. Turns out that transfecting A cells doesn't work when I do it (though it is routine procedure in my lab). Nothing, nothing at all. There's no point in doing the next step, with alternative or otherwise B cells. Now what? Blog, I suppose. Maybe some beer.

Friday: Strategize? Re-evaluate? Retire?

I am a shining example, I tell you.

Friday, March 7, 2008

I Like Being a Scientist?

Something interesting happened to me recently. I've had a busy few months: I went to India, for a wedding (mine), came back to the US and to work. Pounded out a bunch of experiments before I left and few since I returned. Struggled badly with jetlag (it only gets worse!), cultural disaffection, being tired and ill, loads of pressure from the boss and truly pernicious lethargy.

And now I want to work. I want to do experiments, read immunology, gossip about science. I even looked up job openings in India, because I think I want to start my own lab there. I want to keep being a scientist.

It's difficult, rarely rewarding, massively underpaid and a niche profession if I ever heard of one. My job prospects in my home country are limited, to say the least, aside from the fact that I have never actually worked in India. I have done all my research in the States and am, for all practical purposes, an American scientist. I have a new husband and our busy life together. I need some sexy papers, and some powerful, original ideas. I need to push and slog and labour till I can't stand it anymore and my family can't stand it anymore.

Why would I do this? I guess its because I really like being a scientist.
Who knew.