Wrapping up the summer

As the summer draws to a close, I decided to look back on my research experience here at UCSB as a Beckman scholar.  Over the course of the summer, I learned a lot about what it takes to actually do research, from designing the experiments (Who would have thought there are so many little details you have to worry about for each experiment?!) to interpreting the data to presenting my results.  But, not all the educational value of this summer lies in the area of lab work.  Instead, I found that I learned a huge amount from the research and writing classes offered over the summer.  In particular, the powerpoint presentations we had to give at various points in the summer were probably one of the most helpful parts of the internship, even if they were incredibly difficult to put together.  There’s nothing like trying to fit your research topic (which you can probably talk ad nauseam  about) into 3 minutes and 4 slides, while still having your audience understand fully.  Another summer highlight was the Beckman Scholars Symposium, held at the Beckman Center in Irvine.  During this 3 day event, all the interns in the program travelled to the symposium to listen to the guest speakers and present their research (if it was their second year).  Getting exposed to so many different undergraduate researchers engaged a wide breadth of fields was truly a unique experience, I even got a few ideas for my own project from talking to the other undergraduates there.

 

Even though the summer may be coming to a close, my term as a Beckman scholar is only just beginning.  I feel that this intensive summer has served as a great preparation for continuing research during the school year and next summer, but there is still a long way to go.  I look forward to getting back to work in the fall, starting up the year with all my summer experience, which will hopefully make research a little more straightforward this time round!

Smart Materials, DNA, and Kryptonite: Life in a biochemistry lab

Smart materials?  What the heck are those?

Smart materials are more common than you’d think – a lot of people actually make use of them in their daily lives.  If you’ve ever taken a liquid gel capsule (for example an omega 3 dietary supplement) you’re one of those people.  The reasons those capsules are smart is they react and change in response to their environment.  Specifically, in the case of the capsules, they will stay intact in your mouth, but when they hit the your stomach acid they will readily dissolve in response to the pH change.  But a change in pH is a pretty drastic effector for making the capsules dissolve.  What if we could find a way to make them release their contents in response to a more particular cue, like the presence of a particular molecule?

The good news is that such technology exists, right now.  Surprisingly, the basis of this technology is DNA.  Similar to RNA, DNA can also form secondary structures.  DNA strands that form secondary structures as a result of binding a particular molecule, unique to the sequence of the DNA strand, are called aptamers.  Using these aptamers and DNA’s base pairing, it is possible to make a type of chain, one where the links of the chain alternate between aptamer links and normal DNA links.  If the aptamer link binds its unique molecule, it will destroy the chain.  Essentially, this means that every other link in the chain has its own type of “kryptonite”, and the chain will break when exposed to it’s kryptonite molecule.

Now here’s the cool part:  if you take those a bunch of those chains and criss-cross them over a hole in a membrane, you can effectively block transport through that hole, until the chains are exposed to their kryptonite molecule and break apart.  If you put a bunch of these tiny holes in a membrane, block them all with these criss-crossed chains, and place some drugs on one side of the membrane then BAM! you’ve got yourself a smart drug that is only delivered in the presence of a particular “kryptonite” molecule (which, thanks to aptamers, could theoretically be anything!).

Schematic of DNA chain's blocking a nanopore, then reacting to the presence of their target molecule and unblocking the nanopore.

Schematic of DNA chain’s blocking a nanopore, then reacting to the presence of their target molecule and unblocking the nanopore.

But, there’s a problem with this system.  There’s a trade off between how strong we can make those chains and how fast they break apart.  That’s where I come in.  My research project is to optimise this tradeoff, and in doing so figure out design parameters so that the system can also be tuned to fit a wide variety of applications.

Life in a Biochemistry Lab:

My research is conducted in the Plaxco lab through the Beckman Scholars program here at UCSB.  Working full time in a lab is very different form taking normal classes – there isn’t  much in the way of homework or the other usual classroom concerns like midterms.  Instead you find that you have a lot of freedom to take your project in the direction you want (with approval from your mentor/PI of course).  For example, at the beginning of my project I had the opportunity to choose how to monitor the system.  After considering and testing out several different methods, I decided to use fluorescence resonance energy transfer (FRET) as the main signalling method.  With the support of my mentor, I pitched the idea to my PI who approved it, and soon enough I received my first sample.

Labelled Aptamer

Fluorescently labelled aptamer

And in order to actually observe this system, I decided to use a stop-flow fluorimeter (which doesn’t look like much in the picture, but actually has this pretty awesome pneumatic ram as part of the system, which makes it fun to use).

Stopped-Flow Fluorimeter

Stopped-Flow Fluorimeter

Now it was time to begin researching.  The start of the project was the hardest part: I had many new methods to learn and theories to understand. It’s slow going at first, but the learning curve is steep when it comes to research, and in a few weeks I was able to design my own series of experiments that actually worked and resulted in good, useful data.  After running more experiments than I’d like to admit that resulted in either no data or bad data, this was a pretty big milestone.

Overall, I’ve come to understand that working in a research lab really just boils down to a very long series of questions.  Answering those questions takes a lot of time and effort, and the answers you get often just point to many, many more questions.  But even though it might not bring you too much closer to the goal of your research project, there is an incredible feeling of accomplishment that comes from answering these questions, even if its just measuring the simplest of binding curves or finding a melting point, because you’ve done something that might not have been done by anyone else before.  It’s that sense of discovery, and that’s what makes research awesome.