Studying Synthetic Biology at Caltech, by Victoria Hsiao '10

1.      Why did you decide to go to grad school?

I actually decided to go to grad school before doing my Fulbright! As a E:BioE major at Olin, I felt that I would really need a PhD to do higher level research (even though I myself wasn't clear on what kind of higher level research I wanted to do yet). So I applied for both a Fulbright research grant and for grad school in bioengineering during the fall of my senior year. When I was offered the opportunity to do a Fulbright, I asked Caltech if I could defer a year and they said it wasn't a problem at all. My year as a Fulbright fellow gave me the break that I needed after graduating, gave me the chance to travel throughout Asia, and really prepared me for the lifestyle of a graduate student. Since I was working on my own project in an academic lab, my Fulbright experience allowed me to start my actual graduate program with a lot more maturity and foresight than if I had jumped in after my senior year. 


Victoria at Taroko Gorge National Park in Taiwan during her Fulbright 2010-2011

 2013 lab photo 1.jpeg

Working at my lab bench at Caltech 

2.      Why PhD? What's your PhD in? 

After the initial decision to go to graduate school, it wasn't difficult for me to decide to go for a PhD rather than a master's. As a senior, I felt that I had learned a lot at Olin, but that I didn't know enough yet (but can you ever?) and I really wanted to hone my expertise in a single subject. Although I was confident in my ability to learn, I felt very insecure about what skills I could actually bring to a workplace. So I wanted to go to graduate school and just learn a lot more. Of course, I know now that most people learn their job skills on the job, but I am still glad I went to grad school! Additionally, PhD candidates in the sciences get their tuition fully funded and a stipend, while I don't think that's necessarily true for those working their master's. 


My PhD is in synthetic biology, which, broadly defined, is the subfield of bioengineering in which scientists repurpose known genes as part of new biocircuits that they have designed. Our knowledge of biological systems still has a long way to go, but there are many genes with known functions! So synthetic biologists take those genes and try to put them together in new ways. The field is still quite young, so for every project we are always trying to answer basic engineering questions like:


a) Do each of the genetic components behave in a way that we can predict?


b) Does their behavior change when we add other components to the system?


c) If the system works, does it work reliably? In our lab, we work with E. coli as a model organism, but there are labs working with other strains of bacteria, with mammalian cells, and there has even been recent work with gut bacteria in mice. 

My advisor is Prof. Richard Murray, who came into this field from a control systems background, so our lab is very much taking an engineering approach to biology. 

20140729 - Cells from ACS paper .pngA 100x image of engineered E. coli expressing fluorescent proteins 


3.      How has the experience been so far?

It's been great! The BE program at Caltech allows first year students to do 3-4 rotations (one per quarter) prior to choosing your advisor in the summer of your first year. My first year was spent taking classes and doing rotations, which is a great way to get to know a lab. My priorities when choosing a lab were graduation time, interest in research topic, and management style of the advisor. My current lab has a graduation time of 5-6 years and I meet with my advisor 1-on-1 about once a month. Otherwise he's totally hands off but very responsive to email, a style that works well for me. 


I've just finished my 3rd year, and I passed candidacy last summer, so I'm just sort of chugging along in my research! I try to keep normal work hours and usually take weekends off, which I know is quite a luxury in some labs. I attend a conference about once a year, and it's awesome to see all the people that you've only seen as names on papers that they've written (plus you get to visit fun cities like Toronto, Washington DC, or London). With only about 1000 grad students, Caltech is very small for a research institution (but still big compared to Olin), so most labs are open about sharing equipment, or starting collaborations, or interdisciplinary research.   


For the last three years, I've been working on a project where we implemented a negative feedback loop using synthetic protein scaffolds. The protein scaffolds had already been developed by collaborators at Berkeley for metabolic engineering purposes (they bring together lots of enzymes so that the reactions go faster), so we put them into a dynamic feedback loop and used microscopy to track the expression of red and yellow fluorescent proteins in our circuit. We recently published this work so please take a look if you are interested in reading more about it (Hsiao, V., de los Santos, E. L. C., Whitaker, W. R., Dueber, J. E., & Murray, R. M. (2014). Design and Implementation of a Biomolecular Concentration Tracker. ACS Synthetic Biology. doi:10.1021/sb500024b). 


 New Year's Eve 2011 at the Taipei 101

4.      Can you tell us more about this team that you are mentoring at Caltech?

Yes, I am mentoring the Caltech iGEM team this summer! iGEM stands for International Genetically Engineered Machine, and it's an annual undergraduate synthetic biology competition. The idea is that teams of undergrads (5-10 typically) come up with a cool idea for some sort of engineered E. coli that does something new and innovative. Famous examples are E. coli that produce compounds that smell like bananas, or E. coli that are photo-sensitive and so will replicate an image like film. The Caltech team this year consists of six rising juniors, and their project is seeing if they can create a multi-cell regulatory system in E. coli that mimics the glucose regulatory system in humans. The competition this year is taking place at MIT in November and judging takes into account the team presentations, posters, and online wikis.


Actually, the entire reason that I even heard or knew about synthetic biology before to applying to grad school is because I was a part of the Caltech iGEM team in 2008, the summer before my junior year. I was applying for summer research programs and Caltech has quite a few summer undergraduate research opportunities that are open to people from outside schools (Caltech SURF/Amgen program). This one just happened to catch my eye. It wasn't until I started the project that I fully understood how cool it was that we could genetically engineer these bacteria. 


5.      What advice would you give someone thinking about attending grad school?

Prior to starting my graduate program, I received some great advice from older and wiser people, which has helped me set myself up for a good PhD experience. Here it is:


Choosing your PhD advisor is the single most important decision you will make in graduate school. Having an advisor you get along with can make or break your graduate career, so one shouldn't choose an advisor just because he/she is extremely famous and has been awarded every prize. When you're meeting with a potential advisor, it's reasonable to let them know what your expectations are in terms of graduation time, and to ask them what their expectations are of their students. Also, definitely ask the grad students themselves what their work schedules are like, and how long it takes people to graduate, and what sort of jobs people get afterwards. If rotations are an option, I would highly recommend them, and ask other grad students which advisors they would recommend. Also, even if you think you know which lab you want to work in, keep an open mind. I hadn't even considered my current PI before my first-year roommate (who was an older grad student) suggested that I meet with him. 

Posted in: Alumni Speak, Graduate School, Research