by Megan Sperry
Photo courtesy of TEDx.
Shree Bose is a rising senior at Harvard, winner of the 2011 Google Science Fair, and co-founder of Piper, a Minecraft toolbox for budding engineers that allows users to build electronics easily with real-time feedback in the game, with the goal of beating Minecraft. She is also one of Glamour's Top Ten College Women of 2015. After reading the short blurb about her work in Glamour magazine earlier this year, I wanted to learn more about her educational company, Piper, and what she hopes to do next...
Shree first started doing research in high school and her work led her to enter the Google Science Fair.
1. What first inspired you to enter scientific research? When you first started contacting universities to find a lab to work in, why type of response did you receive? Do you think more research labs should welcome high schoolers?
When my grandfather passed away of cancer, I remember the first thought in my mind actually being that I wanted to learn more about the disease itself, so I started reading journal articles, watching YouTube videos, and basically doing everything I could to actually give myself a little bit of background on what I wanted to start researching. When I started reaching out to professors, I honestly didn’t expect to get so consistently rejected, maybe because of my sheer blissful ignorance of the world academic research. Ultimately I think it’s always a calculated risk for professors who are contacted by high school students - between the level of commitment to the research and the lab weighed against the training and the level of independence high school students can bring. However, I think one of the most unique aspects these high school students can bring is innovative new thinking. Once you have been in a field for a number of years, it’s often quite easy to accept the way things are, and when you’re young, there’s the advantage of not knowing the ways things should be. So I think having high schools students who are dedicated and passionate to the work is a really beneficial experience for both lab members and for the students. It’s not always viable for all labs, but it’s definitely worthwhile for the right students.
Shree's research in high school (and her Google Science Fair Project) focused on understanding drug resistance in ovarian cancer. She found that one protein in the cell - AMP-kinase, changes function between sensitive cells and resistant cells.
2. Have you continued your research in chemotherapy resistance and ovarian cancer? What are you interested in now?
My scientific interests have taken some pretty crazy turns since I became involved in research as an undergraduate. In my first two years, I actually took some fascinating courses which taught some of the basic techniques of research in cellular and molecular biology, and I found that I wanted to really be on the cutting edge of working with innovative new methods, which led to my research last summer at Janelia Farm Research Campus (a Howard Hughes Medical Institute campus out in Ashburn, VA) working with neurobiology and motor control in mice. Currently, I’m working in a lab at Harvard Medical School under Dr. Gary Yellen, a really brilliant professor developing fluorescent biosensors that allow imaging of metabolic conditions in real time. This allows us to do really cool things like seeing how cells are processing energy when they are exposed to different fuels. Interestingly, one of the new sensors in the lab reads out the ATP:ADP ratio, which is what AMP kinase (the protein from my high school science fair project) does as well.
Piper is a Minecraft toolbox for building and inventing electronics. What is Minecraft? At its core, it's a game about placing and breaking blocks-- but has been expanded to include activities such as exploration, crafting, and combat. It is perfect for inventing because it is a sandbox independent video game. Read more about it here.
3. Where did the idea for Piper come from? How did you and co-founder, Mark, meet? The rest of your team?
So Piper actually grew out of a lot of the mentorship work that I had a chance to take part in after the Google Science Fair. As a young student who was getting to speak to other young students, I remember often being asked about how I got started with my work, which I generally answered with the advice to find a lab and get involved in hands on work. However, when students asked me about their interests in tech and wanting to get started with engineering and building electronics, I really didn’t have good resources to be able to recommend, and upon looking into it a bit more, I found that nothing really substantial existed - something that was both simple enough to pick up and start doing but also had the engagement that made you want to pick it up and start playing. So I actually met my cofounder, Mark, while we were both working at the NIH together, and as [Mark was] a graduate student who was heading off to Oxford to studying bioengineering, we shared a vision of what engineering education could be. Joel, an incredibly accomplished Stanford student who had studied at MIT, later joined on as a founder and has been a tremendous asset in creating Piper to what it is now, and we have had so much support and bits and pieces of the entire product and development done by incredible people who believe in our vision as well.
Piper and its components.
4. How did you decide what worked best inside the product Piper? (i.e. raspberry pi, circuit boards, etc.) Did you have many permutations of what Piper was? What was the brainstorming process like?
We had decided pretty early on that we actually wanted to use the Raspberry Pi as our central piece in Piper because the support community was huge and we really wanted to open up creating a lot of the content to the community as well. From there, a lot of the hardware was really decided from seeing what fit with the basic electronics concepts we were trying to teach and what fit well with the storyline we were creating as well. From the very beginning, we wanted something very open.
5. Who is your target audience? Do you envision schools purchasing it?
Right now, I think our main target is really 7-15 year olds (middle school age range). We’ve found that that is the perfect age where students are really into the game Minecraft and they are still very open to learning and building. Starting with Piper, we hope that these students go on to fall in love with engineering and with technology, and that they might be able to join more opportunities for robotics and engineering in high school and college. At the moment, we’ve had a few requests from schools, and we’ve actually done most of our testing in schools, which has allowed a different dynamic in the classroom as students really engage with the game and with each other. The teachers and students seem to love it, so we’re creating something that we hope everyone enjoys - even in classroom settings.
6. Piper is pretty expensive right now at $199-299. Do you see this price coming down after the first launch to make it more accessible for more kids?
The price is definitely something we’re trying to bring down, since we really want to get this product into the hands of kids all over the world and get them started creating and discovering. We’re really hoping that after these first shipments from our Kickstarter orders (for which the price is a little higher because of the need to set up suppliers and assembly lines), that will be able to drop the price and make Piper even more accessible. :) Stay tuned.
7. What adds-ons or future directions do you see for Piper? Do you see it as more than a single product? Do you see it as a brand?
I think Piper really grew out of a passion that Mark and I both had for creating tools to get kids excited in science, and we really want to see kids being able to share their creations in way they never have before. At the moment, what we are creating is really a storyline with challenges to teach some basic electronics engineering concepts, but we’re also planning to include a sandbox version where kids can use the tools they’ve learned to create their own levels and gadgets, and then share it with the world. From there, we hope to be able to have some type of monthly subscription where we can ship out new awesome cool projects. Ultimately, our gauge of success as a company is when we have kids creating things that we have never even thought of, and if Piper as a brand can help catalyze that type of innovation, we have succeeded.
8. What are your future plans and goals? Piper and beyond!
Ooh, that’s a tough question, especially considering that my current trajectory is nothing like what I thought it would be five years ago, so my future plans are always changing in new and exciting ways. :) At the moment, I’m applying to M.D.-Ph.D. programs which really strike the blend of being able to create and being able to implement medical technologies and research, so hopefully that will work out for me. We’ll see what happens!
By Heidi Norton
I first ooh-ed and awww-ed at Biomeme’s hand-held real-time PCR machine at An Evening With Philly Biotech a few months ago. Maria Chacon-Heszele, a Life Scientist and employee number 5 at the start-up Biomeme, spoke about her experience in graduate school, her post-doc, and finding her awesome current job. When I started chatting with her after the panel was over, she pulled out of her purse the tiniest, slickest PCR machine I’d ever seen. I wanted to take it home with me, but I wasn’t sneaky enough. A few weeks ago, Megan and I took a field trip to Biomeme’s offices to learn more about this amazing little machine and about Maria’s personal and professional journey (and to give me another chance to steal a PCR machine-- I was woefully unsuccessful).
In case you’re not familiar with PCR, here’s a little background:
PCR, or polymerase chain reaction, is a reaction that creates billions of copies of a piece of DNA using another DNA molecule as a template. An enzyme called a polymerase is added to a tube containing the template DNA, nucleotides (the building blocks of DNA), and mini fragments of DNA called primers that allow you to target the region within your template piece of DNA you want to amplify. Once all of the components are added to the tube, the tube is placed in a PCR machine, also known as a thermal cycler. This machine is essentially a well-controlled heating block; it cycles through the temperatures required for the DNA amplification and at the end of a ~35 cycle reaction, you end up with billions of copies of the specific fragment of interest from your original DNA template. Real time PCR is very similar to standard PCR with one important difference: a fluorescent dye binds to the DNA that is being synthesized, which allows you to measure in real time how much of your newly synthesized DNA is present.
Even before we enter the building, I’m envious of Biomeme’s workspace. N3RD street sounds like the perfect place for a team of scientists and engineers to work creatively and own their nerd pride. Megan and I ring the bell and get buzzed up. We’re greeted by Maria and a friendly looking guy sorting through the recycling and debating about whether the next day is trash day or not. Megan and I already know Maria, but we introduce ourselves to the guy. It turns out he’s Max Perelman, the CEO of the company. We quickly learn that everyone in a start-up wears many hats --- and today the CEO is also the Trash Sorter.
Maria gives us a tour of the office. It’s a big open space with loft style windows, white brick walls, and a big sliding barn door. One of the spaces we are instantly drawn to is in a nook by the windows where there are gleaming metal lab benches, pipettes, tube racks, and bottles of reagents. It’s a familiar environment for Megan and me, but it feels different here. Maria tells us that if we recognize a piece of furniture, it’s because she built the lab space out of various Ikea parts. My favorite is the red open bookshelves that house reagent bottles, gloves, tubes, and DNA extraction kits. (They have to evaluate their DNA extraction technology compared to their competitors.) We continue further into the space and come to a second lab bench, and then a kitchenette, followed by a sitting area. At the far end of the office is the actual office – an open space with great windows where everyone’s desks are located.
Next up is a product demo. Megan and I are going to test our DNA to see if either of us has a single nucleotide polymorphism (SNP) in the MTHFR gene. (The MTHFR gene codes for an enzyme that is involved in the conversion of homocysteine to methionine. 40% of the population has the SNP, which could lead to a decreased efficiency of the enzyme. People who have the deficiency might want to take active folate supplements, particularly when they are pregnant. Testing for this SNP makes for a great demo because it’s not diagnosing any severe illness but the results still have implications in health) Let the experiment begin! Maria takes us over to one of the lab areas, asks us to put on safety goggles and gloves, and gives us a swab to start scraping cells off of the insides of our cheeks. We’re going to extract our DNA using their kit and then test it for a particular mutation of the MTHFR using their hand-held real-time PCR machines. It’s the easiest DNA extraction I’ve ever done (and I’ve extracted DNA from a lot of things over the years—sheep’s blood, strawberries, and neural stem cells to name a few).
Here’s how to prep a sample for real-time PCR the Biomeme way:
5. Drink a beer and interview an awesome woman while you wait for your results.
Although there are a ton of things that I think are really interesting about Biomeme’s products (the lyophilized primers, the ease of use, the huge steps this device is taking in making science more accessible), the thing that I just can’t get over is that the device uses the docked iPhone’s own camera to read out the fluorescent signal. Maybe I should be putting my phone’s camera to more use than taking endless pictures of my dog….
Ok, so a hand-held real-time PCR machine is really awesome. But what can you do with it? Maria tells us about a science class that genotyped their sushi to see if what the menu said they were getting was actually what they got. They found that a lot of fish are actually substituted for far less expensive fish. (Warning: tuna is often substituted for escolar.) Beyond the classroom, this device has the potential to seriously change the way biological field research is done. Researchers who have to hike for weeks to a remote destination in order to collect a sample of a rare frog’s egg, for example, can test the sample on the spot instead of risking the integrity of the sample on the trek back to the lab. Researchers would also be able to pivot more quickly in the field, adapting and forming new hypotheses and experiments based on their results.
Although it’s a bit far off due to regulatory hurtles, the implications this device could have for community health are endless – including genotyping a viral strain and testing for STIs.
After we load our samples into the slick little devices, Maria offers us some beer that her co-workers brewed themselves. We sit down in front of the barn door and start asking Maria about how she got to where she is today.
Maria always loved science as a kid, and she took pride in it. “ I became comfortable being the nerd in the room, and then I [learned to] own it and it became a badge of honor.”
She grew up in Venezuala and moved to eastern North Carolina when she was 15, right before her junior year of high school. We ask her if it the transition to American school was easy or difficult. She says, “Was it easy? The theory I had already covered. But we didn’t have the equipment and the hands on experiments [in Venezuala]. We had to be a lot more creative to do any sort of experiments. I was going to a really, really good private school in Venezuala and we didn’t have laboratory resources, [especially] compared to my public high school in eastern North Carolina. Chemistry lab [at my new school] was heaven for me. But getting used to actually doing scientific experiments was challenging.”
One of the projects she was given at her new high school really stuck with her – she was charged with the task of identifying and studying an unknown ion. Her ion was iron, and so she started researching hemoglobin. She was fascinating by the structure and how fetal and maternal hemoglobin are slightly different, which allows for gas exchange between the mother and fetus. I was like, “Biochemistry, hi! Where have you been?’ It really cemented in my head the idea that not only did I want to do science, but I wanted to get really deep into the science.” She knew then that in 10 years she would be getting her PhD in biochemistry.
Maria double majored in biochemistry and chemistry at East Carolina University in Greenville, her new hometown – and she finished in 3 years! So, as a 20 year old, she headed to Georgia to pursue her PhD at Emory.
She begins telling us about her PhD experience by saying, “I switched labs at the end of my 4th year in graduate school.” Megan and I both say, “Whaaattt!? Tell us about what happened!”
“I definitely struggled at the beginning of grad school. I loved science, and I was interested in studying the biochemistry of muscle atrophy. The project was really cool, but it was really, really tough. I spent about 3 years making reagents because I had to clone these viruses with minimal training because no one in my lab had been doing adeno viral cloning before. These were reagents that other labs already had before I began grad school, but they didn’t use NIH funding so they didn’t have to share the reagents. I got to learn a ton of molecular biology and biochemistry working in that lab. I think I was a little young, starting grad school at 20. I wasn’t a very assertive person – that’s something I’ve really had to work on. So I struggled a little bit with communicating my difficulties with my PI. By the end of my 4th year, I was finally able to get some of my reagents to work, but 2 major articles came out back-to-back in the same issue – 15 people per paper doing the same project I was trying to do on my own. I stuck in the lab another few months, but it was like – I have to start over. So it was either stay in that lab on that project, which wasn’t happening, quit science all together, or find a new lab. I chose to find a new lab. My program was incredibly supportive. My new PI took a big leap of faith, taking me in, but she did. I went from muscle atrophy and metabolism to the cell biology and development of the inner ear. After I joined that lab, I finished in 2 ½ years. I busted ass. I stayed in lab as a post-doc for a year afterwards to make sure my paper got published. It was actually a cool paper and I’m still very proud of it.”
She tells us a bit more about her challenges in grad school:
“Grad school can be really tough for reasons you don’t imagine. For me, the tests and the hours weren’t the reason grad school was hard. It was all of the other stuff.
It was the first time in my life that I felt average. Science was my thing, science was my baby and it was such a core part of my identity. It became very hard to admit that I was struggling and to realize that everyone I was working with was so freaking smart. The imposter syndrome thing – it’s a real thing.”
She gives us a bunch of sage advice for graduate school:
“Don’t just rely on one mentor. No one person can help fulfill all the aspects you need training on – from the personal to the technical. It’s unfair to expect one person to help you with everything.”
“You need to take ownership of your career. It’s okay to make decisions about how you’re going to spend your time. Don’t allow the feeling that you have to be in lab all of the time to take over your life, because you’ll burn out. Sometimes your most creative insight happens when you get to step away from the bench for a little bit. You get to interact with people who have an idea or know something that could be the key to fixing that experiment you couldn’t fix.”
After she wrapped up at Emory, she moved to Philadelphia to do a post-doc at Penn studying cilia in the kidney. A year and a half into her post-doc, literally two weeks after her husband moved to Philadelphia from Georgia, her PI announced he was moving the lab to South Carolina. Maria knew that wasn’t an option for her, so she began to look for other opportunities. She’d been exploring careers inside and outside academia for a while. “I feel like if your heart’s not 100% in it – I want to be a PI – you owe it to yourself to explore other options. Even if you know you want to be a PI, it’s a good idea to learn about other paths so you can make an informed decision.” Part of her exploration of other paths took her to NextFab, an awesome facility (check out our article about it here) for all the DIY-ers out there. At the time, Biomeme had their offices at NextFab. She got to meet the 3 founders of the company and when they showed her their hand-held PCR machine she told them, “You’re lying!” She couldn’t believe it. Similarly to me, she wanted to steal it (it would fit into a purse so easily!), but instead she gave them her card and said, “I know you’re super small, but when you’re ready to grow, please keep me in mind.” And then they told her “Actually! We’re looking for a biologist. Here’s the application.” So she applied, and 4 weeks later she was hired.
She tells us a bit about how exciting her job at Biomeme is now – how many hats she wears (lab designer, manufacturer, experimentalist, study coordinator), and about some of the projects she is most excited about. They are collaborating with a team in Sierra Leone to use their device for Ebola testing. They’ve also partnered with another group at nearby Drexel University to explore the role of their device in point of care STI testing. She’s incredibly excited to get the results back from both studies.
But for now, it’s time for the results of our PCR study --- do either Megan or I have the MTHFR mutation?
We walk back over (ok, it’s like 2 steps) to the 2 little thermal cyclers. The screens of the phones are displaying fluorescent signal versus cycle number, with a threshold drawn. The curve of my data has crossed the threshold, while Megan’s hasn’t. This means that I’m a mutant! Cool!
I can’t think of a better way to spend an evening than extracting [my own] DNA, drinking home-brewed beer, chatting with two awesome women about science and life, and learning that I’m a mutant! I really wish I had stolen that thermal cycler so I could start genotyping my Bonsai tree….