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.

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.

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

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.