Thursday, February 25, 2010

2010 A Year of Hard Decisions: How to pick the best choice for a graduate program.




Recruitment Weekends Rock!
This past month has been a bit of a whirlwind for me. From just finishing up my applications to getting invited to visit my top choices for school, its been very rewarding to say the least. I visited UT's Cell and Molecular Biology Program on Jan 28th and 29th. Working in the building where the recruitment events were located was a bonus, as I got to finish up an experiment I was working on during the downtime at the end of the day. The event started off with a mixer at a hotel downtown where the non-local recruits were staying. The next morning we listened to some talks, went to a gigantic poster session and had some interviews with Faculty. The evening was topped off by a formal dinner and "magic show" downtown at Esthers Follies.

They say that everything is bigger in Texas, and the CMB program has over 120+ faculty associated with the program and growing. This is some consolation because even after working, living and breathing research at UT for over seven years, I still met Professors that I have never seen or talked to before. It was a great victory lap feel for me because of my lack of success at getting in last year and my residual envy of the recruits who did.

The Rice Biochemistry and Cell Biology interview was just as great of an experience. First of all, they flew me in on Thursday Feb. 11th and out again on Feb 13th. I know I could have driven but we only have one car and it would have been troublesome. Upon arrival, not only did they put me up in a great hotel, but my suite-mate got snowed in leaving me alone in what had to be 800-1000 sq feet of posh hotel excellence. The next morning I found out that only five recruits made it that weekend. The other two got snowed in. This was a bit of a shocker for me as UT had at least fifty people in attendance. Granted that was for CMB, Biochemistry and Microbiology, but vast difference in scale reminded me of how exclusive the "Texas Ivy" remains. Rice has some truly gifted Faculty. I met with six for interviews and each one seemed like they would make wonderful advisers. To cap the wonderful day Prof. Jonathan Silberg took us out for some of the best Thai food I have eaten.

Those recruiting visits presented a glorious end to the application season.

Invitations to study

I have since received invitations from both programs. This is very exciting news as less than a year ago I was furtively coming up with alternative career paths in the event that I didn't get into graduate school this year. Now, I had the pick of the litter and the hardest part is figuring out which top-ranked research institution will provide the best location for both both of our careers.

How to decide?
1) For those with a "pseudo-two body problem", consultation is absolutely necessary. This doesn't mean convincing or arguing, but a frank and dispassionate discussion with all the information on the table. A conversation devoid of personal desires and only hoping to find the best solution together.
2) Prayer and Meditation help to put things in perspective. There are a few prayers from the Baha'i Writings that really capture what I want better than I ever could.
3) Just roll the dice. We can't see the future and just have to try to make the best choice with the information presented to us.

Tuesday, February 9, 2010

A Vision of my Career: Finding the Alchemist Stone for the 21st Century

My favorite alchemist Hennig Brand by Joseph Wright.

These are exciting times for me as I gear up for recruiting weekend Rice and meditate on UT's recruiting event. I am preparing for the upcoming interviews with some of my favorite Professors by reading their papers and figuring out who I am and what I want to do. Today I will share with the entire world (or just those that reads this blog) why I do science and what I hope to accomplish in my career as a researcher.

Once, I dreamed of molecular dynamic simulations and being able to engineering enzymes to order. As I survey the field of protein engineering, I feel that we are in a much better place as far as making enzymes to order than when I first started following it in 2004. Now I feel that the struggle is to take the next step and build pathways to order. Perhaps I am overestimating the power of directed evolution, but I am confident that its only going to get easier.

My current vision of the work that I want to develop over the course of my career is the use of microbes (bacteria and yeasts) as chemical factories. Now we can use molecular cloning tools to copy & paste whatever enzymatic pathways we want into them, requiring only sugar for their augmented metabolism. I can't help but draw a parallel with the famed Alchemist Stone, which was reputed to turn lead into gold. This "alchemist stone of the 21st Century" will be the methodology combining protein and metabolic engineering. Believe it.

In stepwise manner we turn lead (sugar or cheaper carbon sources) into precious gold (i.e. expensive pharmaceuticals and specialty chemicals):

1) We select a production chassis. This will probably be bacteria (E. coli) or yeast (S. cerevisiae).

2) We clone out the production pathway from libraries or other organisms into our chassis.
a) If no enzymes exist for that chemical reaction, protein engineering provides a toolkit such as directed evolution to evolve it from similar enzymes.
b) Computational simulation provides an alternative to directed evolution by making educated guesses about mutations which may produce that activity.

3) Next the pathway must be optimized in the microbe for maximum flux. Techniques for this involve modeling the pathway based on production in intermediates and up-regulating the steps acting as a bottleneck. This can be done one enzyme at a time or using directed evolution.

4) Now that the pathway is in the microbe and producing the most of our "gold" possible we can opt to switch its "lead" to something else which is cheaper (plant biomass, recycled plastic, or even urban refuse) in similar manner as putting the production pathway in.

5) Last we can include a production "switch", in the form of an inducible promoter, that we can turn on to push the microbes to the limit before we spin it all down and collect our hard earned prize.

These microbes can be freezed down, dried out and otherwise sent anywhere for production of your product. Thus technology transfer within a company or between countries is easily facilitated. The final purification may be tricky to get setup at a biochemical plant, but growing microbes is easy and straightforward.

Tuesday, February 2, 2010

Therapy lets paralyzed rats walk again; Old News is still Good News


Here is a really cool nature article from back in September, while I was on break from this blog.

Transformation of nonfunctional spinal circuits into functional states after the loss of brain input

And the synopsis from Science Daily.

These rats hat their spines cut to prevent any movement of signals from their brain. Then their walking movement was restored using a combination of electrode stimulation and drugs.

While we aren't quite there at repairing the damage to the spine, by recreating that movement your muscles can retain/rebuild their memory which will be helpful in physical therapy.

As a child, after learning all there was to know about dinosaurs, I moved on to dreaming about making prosthetic limbs. My plans of going into biomedical engineering ended when my parents gave me a book on Genetic Engineering, but I still love to hear about exciting developments for the physically impaired.