This week I spoke with Sarah Sandler, a third year PhD student in the Keyser Group here at Cavendish Laboratory. Originally from Long Island, NY, Sarah’s work focuses on bio nanotechnology, where she engineers and designs solid-state nanopores and DNA nanostructures to act as diagnostic devices! Hello Sarah!
Hey Sarah! As an introduction, could you just tell me a bit about yourself?
Hi Tara! I'm Sarah, I’m a final year PhD student in the NanoDTC and I'm from Long Island in New York. I did my undergraduate degree also in the US in South Carolina, where I studied materials science and engineering. After my degree, I went to Cambridge do my master’s degree and now I’m doing my PhD in physics, specifically in biophysics.
A lot of people who come here to the NanoDTC have studied material science, is material science engineering different?
I think it's pretty similar, but my degree had more of a focus on applying engineering principles to materials systems. In the first year, you study general engineering, which involves taking general engineering classes with lots of maths and coding, which you might not take as student who just studies materials science. Then when select your engineering major to be materials science engineering in your second year, you start to study the underlying science and maths that effect the interactions between the structure, properties, processing and characterization techniques to quantify material performance.
I really enjoyed it because you take lots of interdisciplinary classes. Such as transport phenomena and quantum physics, which are more physics focused , but at the same time if you choose to focus on polymer science, you’re taking advanced organic chemistry to the same level that the chemistry majors do. Because of the way these classes were taught, I think I’m able to approach problems with more of an engineering mindset rather than just theoretical or scientific mindset.
So how did you find yourself doing the PhD you’re doing now?
That’s a great question! When I was younger, I read a lot of books. I'd go to the library and just look in new Science and Technology and choose random books all the time. One day, there was this book called The Sharks Paintbrush that I was like, oh, cool, that must be about sharks. And I loved biology, so I thought the book would be perfect. But it turns out, the book was actually about biomimicry.
Biomimicry?! That sounds complicated! What actually is it?
Basically, it's when you design and engineer things based off nature. Throughout highschool, I raced on competitive swim teams so one of my favourite examples is competitive swimmers suits. There is a type of suits made by Speedo called Fastskins and they're designed to have the same sandpaper-like texture as shark skin does.
I thought the book was really cool, and at the time I was considering studying something related to marine biology. The book made me realize that engineers could actually use marine biology and nature to innovate which in turn inspired me to study materials engineering!
It’s clear you have a lot of interests! What made you decide to do the NanoDTC?
I wasn't really sure what I wanted to do exactly because I found everything really interesting, and I liked jumping between different fields of science. That's why I loved materials because I got to study the applications of chemistry and physics. I even did a minor in microbiology because there wasn't enough biology in the materials course for me! But I just loved all the sciences. I wanted something interdisciplinary, I guess, which made the NanoDTC the perfect fit. In the first year, you have to do lots of practicals in different labs and meet people from different departments that have chosen different things for their PhDs. I really wanted to learn more about the different areas that I hadn't really touched as much on in my undergraduate degree and I think talking to others about things they are passionate about is the best way to learn!
Was the move from America to Cambridge difficult? Did you have to adjust?
I don’t really think so! Throughout my degree I was obsessed with traveling. I was really interested in environmental policy and one day, I got an email about the ‘Global Policy Scholars Program’. I immediately thought it sounded perfect for me. It first interested me because it involved taking some philosophy classes and weekly small discussion groups throughout all four years of the undergraduate degree, which I felt like would take me out the engineering bubble. The best part however I hadn’t initially realized was that you also got a two week trip to Europe at the end of the term! Twelve of us were chosen who had different interests and after completing the projects and core work, we went on a trip to Paris and Berlin. I remember I initially wasn't that excited because I never really travelled that much growing up. But after the trip I realised how much I loved to travel. It totally changed my point of view, and I became addicted. The following summer I moved to London to work at the Royal Institutions of Great Britain as part of UCL’s healthcare biomagnetics lab for three months. Following that, I did an entire semester of Mechanical Engineering in Australia! I just couldn’t get enough of travelling!
That sounds amazing! What place really stood out for you? What place did you think was absolutely amazing?
My favourite was definitely New Zealand. New Zealand is a beautiful, friendly amazing country.
During the Easter break, I could have gone home to one of my friends’ homes (most of them were from Australia!), but I really wanted to go to New Zealand! I really wanted to do one of these great walks and I kept thinking about it and wondering, should I go alone? I remember lying in bed one night and thinking how much I wanted to go! I went online and there was one bed left in the huts on the Kepler Track for the dates we had available for vacation, and I thought, I'm just going to just do it and book it. It was about two in the morning so I didn’t book the flights for my trip until the next day!
It really was an amazing trip, filled with lots of outdoors and adventure sports (including bungee jumping!!). I think it was especially special because it was my first solo trip. I didn’t even tell my parents I was going alone, they would have had a heart attack!
So after you travelled the world and completed the first year of the NanoDTC, how did you decide on your PhD project?
I was always really interested in the biological applications of materials and I wanted to do the bionanotechnology class here at Cambridge. I knew that was going to be the class for me. When trying to decide my PhD project, I was torn between my current PhD in physics and other PhD projects in chemical engineering or electrical engineering. I met Ulrich, my current PI, when I was applying for masters. He initially told me about the NanoDTC, so the Keyser group was always on my radar. I did a mini research project in his group, and I loved the people and the general atmosphere of everyone there.
When I was working in the group, I discovered nanopores, and I really thought they were the coolest thing ever! Even though I was working on a more fundamental DNA membrane project during my mini-project, I met with Ulrich, explained my interested and we worked to design my PhD project together for me!
Could you explain what your project is on?
Of course I can! My work mainly focuses on nanopores which are like tiny glass straws. If you put a nanopore in a machine and then you shoot a laser and pull at the same time as you're shooting the laser, you end up with what looks like two glass pencils, and at the tip of those pencils is around a ten nanometre sized hole.
What you could then do is cut down that pencil and stick it into a small device, which we call a ‘chip’. On each side of the pencil, you put different reservoirs of liquid which contain salt ions. And then when you connect an electrode, one positive and one negative to each reservoir and apply a voltage, you're going to get the salt ions to flow through that ten-nanometre size hole you have in that pencil. This results in a baseline current of salt ions.
This is where the biology comes in. If you put DNA inside this solution, which is negatively charged, the DNA is going to be pulled towards the positive electrode and be forced to flow through the nanopore. And when the DNA is going through, it's blocking the salt ions from flowing, so creating a drop in that baseline current because of the geometry of the DNA.
What I do is I take that DNA and then I use CRISPR-Cas technologies to bind proteins specifically to certain sequences in that DNA to work as a diagnostic. Because the proteins have an additional geometry when they flow through the nanopore, you can get a signal where you see like a drop in the baseline current and then additional spikes for when the proteins are bound due to the geometry. The idea of it is eventually to be used as a diagnostic.
Often, it’s very hard to detect certain genes as some antibiotic resistant genes like tuberculosis are due to a single base pair change, and to detect this your diagnostic system needs to be very accurate. Being able to have a diagnostic where you could quickly have a protein that will only bind if that single base pair change is there becomes really useful, which is where the nanopores come in!
That’s so cool Sarah! You mentioned CRISPR, for those of us that don’t know what CRISPR is could you explain?
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats , and then Cas stands for CRISPR associated protein. CRISPR is mainly used as a genome editing technology. The way they discovered it is by observing a naturally occurring mechanism in bacteria. If you have a bacteria , a bacteriophage can infect it and use the bacteria as a place to multiply itself. Sometimes, the bacteria can fight back and destroy it and when it does this, it takes a piece of that phage DNA and saves it in its own genome. This means if it ever comes back, it has this protein, the Cas protein, can become activated, know the sequence, and specifically go and then destroy the invader. It’s a defence mechanism for bacteria. But people realized they could actually program it to then also be used in humans or in other organisms to edit DNA sequences.
So you're kind of engineering it to instead use it as a diagnostic tool?
That’s exactly what I’m doing! I think my project is really like a bioengineering project. I like to think when you start your PhD, you kind of turn it into what you want it to be. And because of my background, I've been taking much more of an engineering approach. But the further along I'm getting, the more I'm realizing the fundamental things are also kind of interesting. So now I'm trying to use the nanopore devices not only as a diagnostic tools, but also as a way to understand the fundamental biology.
Throughout your PhD, you also have an industry working with you as well, don’t you?
That’s right! My PhD is also funded by Oxford Nanopore Technologies. They work on a biological nanopore platform using similar devices to the ones I’ve been using but instead as a DNA sequencing tool. Working with the scientists there has been super useful, because when I started using CRISPR-Cas techniques, they had a lot of expertise and advice.
So they provided me with protocols and I had a team of experts available to help me when I had questions. I have a team of five people who supervise me from there, so I meet with them every two months presenting updates. They have different experiences and give unique insights into my results and experiments. I've also visited their labs and they have even trained me on their nanopore platform!
Okay, cool. And as a final question, where do you see yourself going after your PhD? Do you have any idea?
I’m currently applying for postdocs now but not set on academia or industry. I’d really like to move to Boston in the US which is a big biotech hub! One thing I loved about working in academia is the freedom. I absolutely love coming up with ideas, having master students, like you Tara, to try out my ideas! I’m constantly wishing for there to be six of me, just so I could assign different ideas for each of them to explore. I’m also interested in entrepreneurship so have a few institutes in mind in the US which hire post-docs but encourage them to explore ideas beyond academia!
Well, I think that is all my questions I wanted to ask . Thank you so much, Sarah. You've been really amazing. I can't wait to do this one.
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