by Heidi Norton
Megan and I had a chance to Skype with Jen recently to hear about the awesome things she’s been doing at Stanford over the past few years since I graduated. One of the things she lights up talking about is the course she designed, ‘Science of the Impossible’. The class is a freshman seminar – professors apply to teach classes on any topic they propose and once a course is offered, freshman students apply to take the course. The idea is to give freshmen an opportunity to study a topic in great depth or from a new perspective. I took a freshman seminar, and it actually changed the course of my academic career – I was introduced to materials science through ‘Bioengineering Biomaterials to Heal the Body’, a course taught by one of my other favorite Stanford profs.
Now the classes includes the topics mentioned above as well as invisibility, photothermal cancer treatments, and stem cell treatments. “We also talk about technologies that were at one time thought to be impossible but are now part of our daily lives. For example – [we discuss] the history of computing and the Internet so students can really gain an appreciation for what really went into the advances that we now enjoy on a daily basis. When you send an email, there is a pretty amazing scientific chain of events that occurs. Electronic signals are converted into optical signals and transmitted across the Atlantic via undersea cables to wherever the main internet hubs are in the US – and it’s amazing how all of this happens in literally the blink of an eye.”
In the class, they discuss the science behind all of the ideas and technologies they explore, but they also consider the social implications. Recently, they had a discussion about the future of energy and climate change. Jen was able to get professional actors from the Bay Area who had written a series of plays on climate change to come in and perform for the students. “It was really thought provoking to consider what would happen if we continue on this path of using non-renewable energy”. They also discussed the implications of medical advances... what if technology advances to the point that humans can live to be 200 years old? “How would that impact the population of earth, and what would be required in terms of infrastructure and urban living? How can we make urban living more comfortable for people?”
Not surprisingly, this course has become wildly popular. The first year she taught it, 20 people applied and she took 16. The second year, 50 students applied. This past year, she had 300 applicants!! “It’s pretty exciting that so many freshman are interested in taking the class,” she tells us. “Just last week, we were talking about driverless cars, and afterwards this one girl came up – she was so sweet, she was like, ‘Jen, this class has changed my life.’ And I was like, ‘Oooohhh, thanks!’ That’s such a touching comment -- to have someone come in thinking they want to be a history major or a computer science major, but then they’re exposed to all of these different areas in science and see how cool it can be and how much of a difference it can make in the world.”
“For example, kinesin is a motor protein that walks along microtubules and carries pretty vital cargo in the cell. It carries chromosomes or neurotransmitters; it’s also a pretty good signal broadcasting system that tells the cell when it’s ready to divide. But people don’t really understand how this motor protein moves. So about 10 years ago, Steven Block, who’s also a professor at Stanford, realized he could use optical tweezers to get some insight into how kinesein was moving. So his idea was to take a focused laser beam, and use it to trap objects that are a couple hundred nanometers across. So he trapped a polymeric bead that then could be tethered to the motor protein. And then when he pulled on the bead, he could see how the kinesin responded to him moving this polymeric bead. And he was able to infer quite well how this kinesin was moving.
“So optical tweezing in general is a great tool to gain insight into biological systems. But there are two limitations. The first is that you can’t directly trap and manipulate particles much smaller than the wavelength of light. That’s a big challenge with conventional optical tweezers. And the second is that if you wanted to infer information about how kinesin is moving in a cell, you can’t do that right now because you can’t really inject 500 nm particles into a cell and expect things to move around naturally. So that’s another issue. You can’t directly manipulate the molecule; you have to tether it to something that’s 500 times its size and hope that when it’s tethered to something that big that it’s moving the same way.
“So that’s the prelude to say that our group is developing systems that can directly trap and manipulate small particles like proteins, potentially in cells. We’ve designed the optical tweezers, we’ve fabricated them, we have some preliminary characterization results that show that indeed, they are working like we expect them to. And I think that once we’ve fully developed the prototype, this will be a really cool tool for studying biological systems and how a number of biological processes are unfolding in cells with potentially nanometer scale resolution. So that’s the project I’m most excited about -- Developing these optical tweezers that can be used to manipulate and image small proteins within cells.”
I am so floored and excited by the implications of her work that I begin to stutter as Megan and I ask her follow up questions. How does it work exactly? What are your plans? Tell me more!!! “You don’t need to tether the protein to the bead. The protein usually has a diameter less than 10 nm, so based on the size of the protein and its structure, we can trap or target specific proteins and then move it around and see what it does. We have some designs that are agnostic to structure, so you trap everything of a given size. Then there are some proteins that are approximately cylindrical and maybe 7 nm x 4 nm, then you could trap all proteins that fall into that category. But there are certain macromolecules that may have all the same physical parameters – they may be the same size and have the same refractive index, but they may be chiral – maybe they have different handednesses. So we also have different traps that can trap proteins based on what chirality they are.”
What are her plans for applications? They first plan to recapitulate Steven Block’s experiments with kinesin. Second application? “We already have a patent on it – water purification and water filtration. Instead of having just one optical tweezer, you could have an array of optical tweezers. So if you have small impurities in the water, you can trap them with light as they are flowing past, and then have everything move along. So you don’t need a physical filter; you can just have an optical filter. The final application is in the pharmaceutical industry: “A lot of pharmaceutical companies synthesize drugs that are chiral and they spend a lot of time making solutions that are enantiopure. So if we could have a light-driven technique to take a racemic mixture and turn it into an enantiopure solution, that would be really cool. Although that is a more futuristic application because we can’t trap molecules that are just 0.5 nm yet.”
After we say goodbye and close the laptop, Megan and I stay put in the library for a few minutes, basking in the sunniness and joy that Jen brings to a room, even if it’s through a computer screen – we’ve named it the Jen Dionne glow.