Saturday, September 10, 2011

In remembrance of September 11, 2001

American Flag picture - photo of the American Flag

Today, I set aside some time from preparing for my defense to read through the New York Times' tribute to September 11, 2001, and reflect upon what that day and the events which have followed mean to me. I did not expect to feel so profoundly moved as I read through the stories, and in particular, I could not help but feel struck afresh with anguish and cry as I carefully paged through the moving slideshow of the rise and fall of the towers of the World Trade Center.

Still, other articles reminded me of my core belief in our country — in the people of our country. In spite of the willful erosion of personal privacy and civil liberties and civil tongues, in spite of the tragic sacrifice of human lives both domestic and foreign, in spite of ongoing anti-intellectualism, in spite of continuing sexual, religious, and racial intolerance, in spite of a bitterly polarized political climate, in spite of our continued mismanagement of our environment — in spite of all this, I still believe that the story of the United States of America is one of hope. If ever there were a country to break pre-conceived notions, to defy intolerance, to unite for a greater good, to show that change can be for the better, to overcome adversity, then it must be ours.

Ten years ago, I stood with friends in an undergraduate dorm room and watched the World Trade Center towers collapse and the Pentagon smolder. Now, here I stand to defend my Ph.D., and I can not help but feel grateful for all the opportunities I've had thanks to having a life here in the USA. I am not always proud of our country's actions, but I am proud of what our country stands for: truth, liberty, and justice for all. Our story is marked by tragedy and marred by missteps, but it is, indeed, the story of hope. I will always remember.

Tuesday, August 9, 2011

The bog of eternal singlehood: college towns beyond college

Life in a college town

As I apply for jobs, many of which, for better or worse, are at academic institutions, I keep having a nagging feeling tugging at the back of my mind, like the tantrum-throwing three year old desperate for that Yo Gabba Gabba doll tears at her parent's arm in aisle 14 of the local Target. This pressing thought which brings me so much strife: I'm just not sure if I can take living in yet another land-grant college town.

Don't get me wrong—there are many great things about living in a college town. Life is generally quite pleasant and quiet, save football weekends. The cost of living is usually fantastic. They also tend to be family friendly, with quaint little farmers' markets and little local restaurants and shops. They also tend to be fairly progressive and open-minded, and support culture and art to a greater extent than you'd expect from such a small population.

Yes, for many people, a college town is a rather idyllic place. There is a specific subpopulation in these college towns, however, for whom the experience becomes utterly hopeless. This subpopulation: those who move to college towns, are not college-aged, and arrive without a significant other. Meet those requirements, and you're basically hosed until you escape. It is the bog of eternal singlehood.

I mean, let's take an honest look at the candidates in the dating pool in a college town for those who already hold one or more higher education degrees:

  • College kids: I'm sorry, did you not see the word "kids" there?
  • Grad students: Emotionally unstable semi-adults who incorrectly concluded that the panacea to their life problems was to get yet another degree.
  • Postdocs: Does the sound of frantic typing as they try to finish their latest lit review during the act of love-making turn you on?
  • Junior faculty: Ah, the less youthful, less healthy, more stressed versions of postdocs. Yes, I'm sure you had a good reason behind that choice...
  • Staff: They probably arrived there because of a significant other; if they are single at this point, they're looking for an opportunity to flee, not to stay.
  • Hipster/Hippie Townies: It's okay, so long as their friends never find out they're sleeping with you. Oh wait, it's a small college town...
  • Folk in the surrounding countryside: don't be surprised if you're viewed an over-educated, heathen, pinko socialist who never learned how to do anything actually useful (all of which could be accurate assessments)
  • People in the nearest city... five hours away: They're already pairing up with equally smart, young, attractive, better-paid competition that had the foresight to not force the issue of a long-distance relationship on the first date.

As a consolation, you will find great friends, for whom your sad, lonely, single self will serve as a reminder of why they need to stay committed to their own relationships.

With complete seriousness, I've found a tremendous amount of personal growth in the college towns I've inhabited for the past twelve years, and certainly, the quality of friends I've found in them has been unsurpassed. I admit that location is really only one part of the whole romantic equation.

Anyway, we'll see what the future brings. Maybe I'll finally join the young guns in a big ol' city, myself. Or maybe I'll find the the one who breaks the mold. Or maybe it'll just be the status quo, but hey, there are far worse bogs out there!

Friday, April 29, 2011

Let's talk: designing inter-cellular circuits through synthetic biology

True phone

Thursday, GenBioOrg brought in Prof. Ron Weiss to speak about his work in designing biological circuits, and this crazy, sometimes hyped field of synthetic biology. Prior to Prof. Weiss's talk, while I could appreciate the idea of synthetic biology, I mostly regarded it as a somewhat foolish pursuit, on account of the amount of fundamental biology we still just do not know. In many ways, my field of computational systems biology relies on building and testing models from "Swiss cheese knowledge", where gaps prevail (e.g., protein-protein interaction networks built from yeast-two-hybrid studies with high false-positive rates, or microarray analysis suffering from from the high-dimensionality, low-sample conundrum). Thus, whatever decries the prematurity of systems biology goes doubly so for synthetic biology, for which systems biology provides a central strut. The rationale is, if you don't understand it, how can you manipulate it? Of course, as I've learned repeatedly (but have failed to generalize), "You don't need to understand the internal combustion engine to drive a car."

Well, Thursday afternoon, Prof. Weiss deftly reminded me of this reality through his combination of humility-tempered optimism, his impressive collection of proofs-of-concept, and his insight for possible applications. He presented a number of intriguing biological circuits in his talk, but I felt most excited by his work on pattern formation through synthetic inter-cellular signaling networks (behind a Nature paywall, sorry). In this work, Weiss and his colleagues created a population of "receiver" bacteria cells, which had a genetic circuit that would cause cells to fluoresce (light up green) at a moderate concentration of a molecule called acyl-homoserine lactone (AHL).

To make the receivers fluoresce within a specific concentration of AHL, Weiss and colleagues actually made the receiver cells fluoresce (i.e. "be on") by default. They then created two AHL-detection circuits with very different input thresholds: a high-detection circuit which activates in the presence of large amounts of AHL, and a low-detection circuit which activates in low amounts or in the absence of AHL. Weiss and colleagues wired both detectors to the same output: when activated, they repressed ("turned off") fluorescence. If you're familiar with electronics, you'll see that Weiss and colleagues constructed a NOR gate, where the inputs are "high AHL" and "low/no AHL". If you're a programmer, you might think of the condition for fluorescence as

if not (ahl_level > high_threshold) and not (ahl_level < low_threshold):

Weiss and colleagues then developed "sender" cells containing a circuit that caused synthesis and secretion AHL when exposed to tetracycline. When a colony of sender cells was placed in the middle of a "lawn" of receiver cells and exposed to tetracycline, the sender cells emitted AHL, which then diffused as a radial gradient from the colony, resulting in a concentric ring of fluorescence around the sender colony, but not immediately touching it, like a bullseye. That is right by the sender colony, the AHL was highest, and so the high-detection AHL circuit shut off fluorescence and left those cells dark. A little further out, the levels of AHL that diffused from the senders was at a more moderate amount, so the high-detection and the low-detection circuits remained off, allowing those cells to fluoresce. Beyond those cells, the levels of AHL were too low, and though the high-detection circuit remained off, the low-detection circuit turned on and repressed the fluorescence, again.

Colony of sender cells, fluorescing red, placed in a lawn of receiver cells. The sender colonies secrete signaling molecule AHL, which diffuses through the media. Receiver cells a sufficient distance from the colonies will receive enough AHL to fluoresce green, while those too near or too far will receive too much or to little AHL, respectively, remaining dark. [Image obtained from Ron Weiss with permission, modified by CDL to include labels.]

While this makes for pretty pictures, taxpayers rest assured: glowing cells are only the proof of concept. This research has major implications for practical applications, for example, in stem cell research, tissue engineering, and bioengineering.

As a high school student, I felt incredibly excited to learn the answer to the question, "How can a ball of indistinguishable cells turn into a brain, limbs, skin, etc.?" The answer, as those of you with some developmental biology background know, is "Through protein gradients," and more specifically through transcription factors and their co-activators and co-repressors. Beginning with your mother's egg cell, there already existed protein gradients which pre-determined the regions that formed your head, or your feet, or your inner organs, and as your zygotic cells divided, these protein gradients begot even more protein gradients, in a beautiful choreography perfected through billions of years of evolution. This research by Prof. Weiss and his colleagues demonstrates that synthetic biology may provide a means to not only guiding stem cells (either derived from an embryo or returned to their embryo-like stage) through the difficult process of differentiating into other cell types when cued by specific protein concentrations, but also the means to create colonies of cells capable of producing protein gradients. Through a successful combination of these sender-recipient circuits, we could achieve multiple types of differentiated cells, and maybe even self-organizing tissues, all from the same culture of stem cells.

Likewise, this research has important implications in mixed cell cultures. For example, the liver is primarily composed of cells called hepatocytes, which perform most of the functions of the liver, such as detoxification, lipid homeostasis, and blood plasma production. However, by culturing hepatocytes together with another cell type found in the liver, called liver sinusoidal endothelial cells (LSECs), the hepatocytes maintain their "liver-ness" far better than when cultured alone. Weiss's research implies that we may some day be able to develop synthetic "surrogate" cells to support cells that are characteristically difficult to maintain ex vivo by providing important intercellular signals.

In terms of bioengineering applications, such as biodiesel or pharmaceutical production, a major stumbling block has been the difficulty in engineering biological systems with the biochemical capacities necessary to carry out each step necessary to manufacture a complex molecule. Weiss's research suggests growing practicality in molecule manufacturing by designing chains biological pathways that exist in separate organisms, much as the case for deep-sea vents ecosystems.

Two other profound discoveries that Weiss presented were completely counterintuitive to me: adding complexity to a biological circuit tends to 1) bring about more digital (on/off) behavior rather than analog (continuous gradient from low to high) behavior, and that coupling components tends to reduce noisiness in the circuit rather than increase it. Although I do not have time to recapitulate Prof. Weiss's demonstrations of these emergent behaviors, I encourage you to browse through his publications yourself.

The last two points I'd like to note from Prof. Weiss's talk are the following quips, which I found particularly encouraging (paraphrasing). First:

Computational simulation is absolutely central to synthetic biology. We are beyond the point where we can design biological circuits through intuition alone. —Prof. Ron Weiss
This statement makes me feel validated for pursuing a background in computational biology. Second:
We've been working on a project for eight years now that we still haven't published results from. We're very close, though. It will be just another year or so. At least, that's what I tell my graduate student. And the graduate student that takes the project after she graduates. And the one after she graduates. —Prof. Ron Weiss
Researchers with careers as illustrious as Prof. Weiss's can come in and dazzle us grad students with tales of field-changing success, and I think this gives unreasonable and unwarranted expectations of how our own research paths should go. Certainly in my case I've felt that because I've struggled, I must not be successful, because it rarely seems the successful people struggled. It's refreshing to see an admirable figure in his field open up and show vulnerability by admitting that, even to this day, he has his struggles.

To summarize, here are my takeaway thoughts from Prof. Weiss's talk:

  • The time for synthetic biology research is now.
  • Researchers can engineer cell-cell communication, beginning the era of human-designed mixed cell cultures.
  • Even excellent researchers struggle.

Monday, March 28, 2011

Driven by the pursuit of proficiency


I am looking for a job, and as this is only the third time in my life job hunting, I have sought advice anywhere I can get it. Like most universities, Virginia Tech has a Career Services office, so I consulted their website to help get things rolling. They suggest beginning with a self-assessment, and the very first item of this self assessment bluntly asks, "What do you want to achieve in your work?" While this question is frustratingly broad, it is fair game; one could expect such a question in an interview, and one certainly must have an answer ready.

I have never felt guided by some vision of how my life should be. I mean, sure, when I was 8, I wanted to fly an F-14 Tomcat and shoot down commie MiGs because that made you a hero, and when I was 13, I wanted to be a Marine Biologist because of National Geographic and NOVA PBS shows, and when I was 18 I wanted to be a physician because that's what all biology majors intend to be. Each one of those were fantasies—spurious projections of the possible me, based on the immature and incomplete value system I held at the moment. When I gave up on the gauntlet of medical school my junior year at UGA, I also gave up pretending I could calculate long term career trajectories. Despite blowing off this central tenant of many a cookie-cutter career book and commencement address, I've thus far avoided becoming a complete and utter catastrophe of a human being, so I continue to make without.

Now I'm a grad student in computational biology—the result of a few simple ingredients: 1) I've enjoyed computer programming since high school, and 2) I've found biology fascinating since the days of reading Zoobooks at the dinner table. I have also loved video games since grade school, but I didn't take the career path of a video game programmer because I didn't feel like I would make a substantial contribution to humankind. In contrast, I quit trying to become a physician—a career in which I would have had a direct and tangible impact on other people's lives—because I saw the competition was better than I was at jumping through the med school application hoops. (I also love playing guitar, but let's be realistic—although I've re-evaluated that option and there are worse things.)

According to motivational speaker Dan Pink, motivation boils down to three needs: mastery, autonomy, and purpose (video below if you are unfamiliar with Pink's theory). From that standpoint, I didn't feel a sense of mastery in my quest to become a physician, and I didn't feel a sense of purpose in my pursuit of game programming, but with a decent grasp of biology and a propensity for programming, computational biology seemed a good fit. Now the question stands, has it been?

From the standpoint of fulfilling the need for purposeful work, I have to say I have certainly experienced a boost in motivation after switching research groups, due in large part to shifting the biological subject from bacteria to in vitro liver tissue culture systems, which has more immediate implications for human health—a subject which still motivates me.

Considering proficiency, though, I feel very uncertain about my path in research. My RSS feeds continue to fill up with table-of-contents from journals faster than I can screen them for interesting abstracts. Also, although I don't reading through literature in the field as much as before, I still just dislike doing it. I think this indicates a major obstacle to a career in research because it breaks the virtuous cycle of positive feedback: what we like, we do more of, so we get better at it, which makes us like it more and do more of it, which makes us better at it, and so on.

It's not clear I've grown much as a presenter, either, though it's not for lack of opportunities. I've given at least one presentation a month, sometimes several, mostly to my two research groups, but with some conference and departmental talks, as well. While I've gotten better at recognizing the work pattern that goes into preparing a presentation, I don't feel I've been able to reduce the time it takes to prepare them, and while I feel I've improved in delivery technique, I feel disappointed at how little I've improved given the amount of time I've invested. This said, I have discovered I enjoy delivering a presentation for which I've prepared adequately, which I attribute to the performance aspect.

If we take a look at the most important currency in academia, publications, I'm far from flush, with one co-authorship on a book chapter, one second-authorship on a collaboration paper, and one first-authorship on an original research article (Open Access, yay!). I'm working on another paper currently, and should begin another one prior to defending in June. It's not a sparse record, but it's unremarkable. If I have learned anything from The Dip, it's that I want to do remarkable work.

I really want to become proficient, but after nine years of working in academic research from undergrad, to research tech, to grad student, I feel it's escaping me in this pursuit. My research experience feels like long periods of slogging, largely devoid of any feedback, let alone positive feedback (which is rare and fleeting). I want a research experience that breaks that mold, but I'm willing to accept I might not find one, and I'm becoming more enthusiastic about switching tracks to a career where I can make a genuine success of myself. I want that virtuous cycle of positive feedback. I want to get excited and make things!

So, to the future interviewer who asks, "What do you want to achieve in your work?" I answer this: "I want to achieve remarkable proficiency." Why settle for less? Life is short; let's find a way to become awesome while we still can.

Friday, January 7, 2011

Common Good: Adding a Creative Commons License button to your Blogspot (Blogger) blog

2500 Creative Commons Licenses

I have intended to place the contents of this blog under a Creative Commons (CC) license for a long while, especially given that all the attractive photos I love to use in these blog entries come from Creative Commons-licensed content on Flickr. For those unfamiliar with Creative Commons licenses, they explicitly permit re-use of creative works a priori. Provided you follow the criteria of the particular CC license of the work (usually simply attributing the original creator), you may simply use, or even modify the work, without the need to contact the original creator for direct permission to do so. Read the Creative Commons' website for more detail.

I had let this task linger far too long, so, spurred on by a recent email exchange with Mark Hahnel of Science 3.0, I finally felt the inspiration to get this done. Unfortunately, I didn't find the top-ranked pages in Google searches for placing a CC license button on Blogger/Blogspot blogs very helpful, so I decided to just figure it out. It turned out to be a simple process, so I documented it and present it here, in step-by-step format (all under the CC-BY license, of course):

  1. Go to the Creative Commons website and choose a license
  2. Copy the HTML that CC presents you after you've selected your license
  3. Go to your blog's page, and click the "Design" link in the navigation bar at the top. Alternatively, go to your Blogger author page and click the appropriate "Design" link for your blog there.
  4. Click the "Add a Gadget" link in the design editor (should be one at the bottom of the area).
  5. Click the link to add an "HTML/JavaScript" gadget.
  6. Add a title, like "CC License", paste the HTML of your license button that you copied from the CC website into the contents box, and click "Save".
  7. Optional: You'll be back at the design editor; double-click the new CC License gadget and move it below your Blog Posts gadget (or some other fitting area).

That's it! Your shiny new CC license button should appear where you placed it.