Student Research at Duke

Science has provided us nearly all of our modern conveniences. Better food, clean water, the Internet, vaccines, CD Players, airplanes, and so much more are all products of science that we take for granted each and every day. We generally never stop to think what it took to produce them.

However, scientists have paid dearly in order to further their craft. Galileo was tried by the Catholic church as a heretic; Einstein lost his wife and children in creating the the theory of relativity; and Robert Oppenheimer slaughtered 140,000 people. These burdens were tragic, but the fruits of their labor paved the way for the world we now live in- a world that most of us (hopefully) do not regret.

For some researchers, it is too much to bear. Instead of making the necessary sacrifice, they cheat the system. William T. Summerlin, who claimed to have made skin grafts in mice without immunosupression, was found to have colored in grafts with a marker. Eric Poehlman earned 2.9 million dollars in grant money from data points he fabricated. Former professor Vijay Soman even went as far as to steal his colleague’s research and claim it as his own. All of these men wanted to change the world without following a fundamental law of the universe: there is no gain in a system without a loss somewhere else.

As scientists, we must analyze not only data, but what it takes to perform good science. If this cost is too great for a person, then he or she does not deserve to change the world. We must always keep one thing in mind when we work in the lab: the cost of progress is steep, but so is the price of honor.

The Cost of Progress for the best scientists

A couple weeks back, the National Organic Symposium took place at Duke. During my first week (on one of my slower days), my mentor recommended I go see Dr. Ben Feringa’s Presentation. I was blown away.

Dr. Feringa discussed how his lab had been building molecular devices for use in nanotechnology. He discussed everything from lightpowered mini-switches to tiny valves that would allow individual molecules in and out of a system But by far, his most interesting creation was his molecular motor:

HOLY CRAP! THAT’S AMAZING!

Dr. Feringa would eventually like to reach the point where he can control the movement in a less drunk fashion, and build a miniature windmill park (Yes, windmills…he is Dutch after all). However, he does acknowledge the possibility of a far more advanced future…for better or worse (cue ominous music).

GREAT SUCCESS! After a little hesitation, and a lot of help from the lab members, my Western worked out perfectly. Not bad for the new guy. I’ll post a picture up as soon as I get batteries for my camera.

Every so often in science, a person comes up with a ridiculously elegant idea. Whether it was relativity, evolution, or Polymerase chain reaction, these ideas and methods lead to amazing results, and will forever change the course of science. Now I have found another such great idea- distributed computing.

These guys at Stanford have overcome the immense problem of calculating protein folds by using the world’s greatest supercomputer: the internet. Read more about the project here, and please help them out by donating your computer’s idle time to protein folding. Who knows- you might help cure Alzheimer’s.

Lovely. Only a week, and I am already flying solo. My mentor, Robert, is flying out for the DARPA conference in New Mexico to talk about…what ever high-level scientists discuss. For the time being, I’ll have to run an electrophoresis and a Western Blot…by myself . I really hope I don’t blow away the lab. Wish me luck.

Hoping this guy is not Icarus. Hoping Icarus is not me.

Failure- even the word feels like broken glass in your mouth. In our attempts for greatness, we will undoubtedly have to deal with some failure. For some people, it will be a total failure of a project that yields no results after gallons of blood, sweat, and tears. For most people, it will be failure to be careful. This was the case for me.

Well, readers, you’ve made it this far. I’m now going to take you into the secret workings of 4th floor Nanaline Duke, where the magic of protein design happens.

The Hellinga Laboratory consists of two main sections: the East Lab and the West Lab. The East Lab is the larger of the two, and where most lab members work.

This lab is basically a workshop for proteins. Just about anything you need to build and test a protein is here. One of the tools used to this end is a robot that actually assembles our proteins for us:

Another such powerful tool is the massive Beowulf Cluster supercomputer. This computer is able to perform the arduous calculations necessary for protein folding:

East lab also contains offices for the software designers and the researchers:

Unfortunately, none of those desks are mine. To find my space, we have to go to the West Lab.

The West Lab is kind of like a really big closet; nobody works there, but it holds a lot of stuff we need (such as myself):

However, this lab does house one of our most important machines, our DNA synthesizer (affectionately known as Bertha):

And now that we are back at my desk, I am afraid I must get back to work. However, I’ll be back with a new post tomorrow morning. Until then, have a good day.

So now that you know a thing or two about synthetic biology, how does the lab I work in fit into all this? It all has to do with proteins. Natural proteins can do all sorts of stuff, from catalyzing reactions to fighting disease. The problem is… we do not know perfectly how they work. As mentioned in the previous post, proteins are made of 20 building blocks called amino acids. These amino acids are strung together like links in a chain. However, this amino acid chain does not stay straight for long. Due to the chemistry of the amino acids, the chain begins to bend around and starts to take on a three-dimensional shape (see the picture below). This new three-dimensional conformation is the protein’s functional structure and allows the protein to perform its function. There is a huge gap in our knowledge: what shape will the protein chain take? A chain can be put in space in nearly an infinite number of ways. How do you determine what shape the protein will take on? If we could figure this out, protein designers could start to design their own proteins that perform unique functions that no protein in nature could perform. Furthermore, this protein could be coded into a gene, and then put it into a bacteria to produce a new system that could produce a useful functions (bacteria film anyone?).

The truth is labs from all over the world are getting closer and closer to this possibility each and everyday. And Dr. Homme Hellinga’s lab is one of the closest. Dr. Hellinga was able to create a computer program that took a protein that had no catalytic activity, and transform it into an enzyme that could support life. This is revolutionary. With enough work and modification, one can induce enzymatic activity into any sort of protein, creating all sorts of interesting functions. One of Dr. Hellinga’s coolest ideas in my opinion was creating a protein that changed colors when there was a molecule of TNT nearby. This protein could be inserted into plant seeds. These seeds could then be planted in minefields, and after one season, one could instantly detect where the mines are, and clear them out.

Dr. Hellinga is also working on a process he has dubbed “Protein Fabrication Automation.” Right now, it takes about 2 weeks to make a single protein. Using robots and advanced machinery, Dr. Hellinga has created a process in which it would only take 2 days to go from an amino acid sequence to a substantial amount of protein. Already, it only takes 4 days to get the protein we need for experimentation. With these two powerful tools, Dr. Hellinga’s lab will be able to make any enzyme he wants in a matter of 48 hours (He once joked when we first met that the process was so fast, I could get my PhD thesis done by my senior year once we perfected PFA).

So what am I doing in this lab? At the moment, learning. Everyone in this lab is so much smarter than me (How did I get this fellowship? I’m still quite not sure). I have a lot to learn. My project so far deals with this protein called KDPG aldolase. Aldolase is an important enzyme because in metabolism, its one of the molecules responsible for connecting carbon atoms in living organisms. The ability to induce carbon-carbon bonding in an enzyme may prove useful in the future, so my mentor and I are trying to figure out how to engineer it into proteins. We’ll see how that goes.

Well I’m feeling pretty dandy. I should get back to work. To learn more about the universe of protein design, I highly recommend this article. It tells what universities all over the world are doing in this exciting field, including Duke. Until next post, adieu.

Dreaming of Aldolase….all da’ days (Bad Pun)

Who did not love Terminator, the classic tale of robots traveling through time in an attempt to stop the savior of a postapocalyptic future (only 22 years more until the war begins). The movie always seemed rather odd to me, because in some sense, humans work at the molecular level a lot like machines. In fact, the machinery of living things is far more advanced, given it has had about 4 billion years of testing and research.

It all starts with DNA. DNA is a molecule that is found in all living things. An organism’s DNA holds all the information needed for performing critical functions- from making new cells, to fighting invaders, to genetic regulaton. One can even think of it as a master blueprint.

But just as a blueprint by itself is not a house, DNA by itself is not a living thing. The genetic code it holds is used to build molecules called proteins. These proteins are molecular machines and materials that build, destroy, and rearrange different parts of the cell efficiently. However what makes these proteins remarkable is not just the ability to construct and destroy, but the ability to stop at the right time. This ability allows proteins to function as a living thing. Imagine a house that not only can build itself, but can recognize when something in the house broke, it could fix itself. That is what a cell does each and everyday. What is even more fascinating is the fact that every naturally-occurring protein, from the immensely strong spider silk, to the disease-curing antibodies, are made of the same 20 building blocks known as amino acids. That would be like using balsa wood to make both a model airplane and the Empire State Building.

There is however, a different way to think about DNA. Instead of a blueprint, DNA can be thought of as something you are using right now: a computer program. The genome is nothing more than a huge computer program, and the proteins are nothing more than different pieces of hardware that are manipulated by the software. When thought of this way, its easy to see how humans can be thought of as organic robots.

This is exactly what happened a couple decades ago. Scientists who normally did not study biology- engineers, computer scientists, mathematicians- began to enter the lab. When they did, they began to think about life using the robot analogy. But they took the question one step further. One can change the software and hardware on a robot to produce all sorts of new programs. But what about living things? What if one could take the entire software of life and change all of its pieces, and reassemble them in different ways? What would happen?

Fast forward to the present, and you have synthetic biology. If you would like to learn more about synthetic biology, what has been done, and even how you can get involved, I recommend the following resources:

• Synthetic Biology Wikipedia Entry
• “Custom-Made Microbes, at Your Service” by Andrew Pollack
• The Coolest Competition Ever