by Megan Sperry & Heidi Norton
With special thanks to Dr. Maria Chacon-Heszele (Biomeme), Cassidy Blundell (Penn), and the TechGirlz team for their help with this project!
And thank you to our workshop sponsor, Benchling!
This workshop was held at the George H. Stephenson Foundation Undergraduate Laboratory at Penn.
With special thanks to Dr. Maria Chacon-Heszele (Biomeme), Cassidy Blundell (Penn), and the TechGirlz team for their help with this project!
And thank you to our workshop sponsor, Benchling!
This workshop was held at the George H. Stephenson Foundation Undergraduate Laboratory at Penn.
TechGirlz students matching DNA base pairs.
DNA hacking is all the rage. It’s in vogue—and rightly so. Since 2012, an explosion of DNA hacking techniques have been developed and used to learn about the function of DNA in health, disease, and development. You may have heard of CRISPR, arguably the most prominent of these techniques, which permits cutting, removal, and insertion of genomic material. Think of it as cut and paste for your genome. Unsurprisingly, the technique has caught the attention of established scientists and DIY gene hackers alike, including the advent of home hacking kits on sites like Indiegogo. Although we must be careful with how these techniques are used, they capture the imagination of scientists and non-scientists alike, inspiring people to learn about biology on its smallest scale.
Heidi and Maria teaching and demonstrating the experiments.
Despite these advances in genomic editing, we are still looking for ways to rapidly and accurately identify specific DNA sequences, particularly in the field. Did you know that we have identified only 2 million species out of an estimated 8-10 million species living on Earth? Prior to the development of sophisticated techniques to differentiate genetic codes, scientists primarily relied on the shape, color, and behavior of an animal to identify the specific species. For example, it was previously thought that the butterfly, pictured below, was a single species with 10 varieties of caterpillars. However, using DNA barcoding—a technique that specifically looks at mitochondrial DNA, researchers found these butterflies were actually ten distinct species for which the adult butterfly looks identical. How crazy is that? Just this year, the same discovery was made for the giraffe. Published in Cell, the paper is titled: Multi-locus analyses reveal four giraffe species instead of one. Mind blown.
These are just a few areas currently under intense investigation in the field of genomics. The one piece they all have in common is a strong convergence of computer science and biology, a hallmark of genomics today. We felt this was the perfect topic to develop a TechGirlz workshop around. Genetics is a combination of cutting edge science and technology and is seemingly the stuff of science fiction. What could be better?
TechGirlz is a non-profit that hosts and promotes many events for young women in tech. A core component of their work brings together women who are passionate about science and technology to share their knowledge and excitement with middle school-aged girls interested in these fields. Partnering with TechGirlz and two exciting start-ups, Benchling and Biomeme, we created a workshop that taught students the basics of DNA while also introducing them to what we think is most exciting in this field. Heidi—our resident genomics enthusiast—led the development of this workshop.
Megan Sperry: When did you first learn about genomics? What facts and ideas struck you as the most interesting?
Heidi Norton: I first learned about genomics as a high school student when I attended a Biotechnology Summer Academy and got to spend a week in a sheep genomics lab. I ended up working there for a couple of years throughout high school and got to learn about Callipyge, a fascinating heritable genetic condition in which the muscles of sheep’s buttocks hypertrophy, leading to really, really big butts. In addition to the very memorable phenotype, the coolest thing about this condition is its mode of inheritance – it was found to be neither dominant or recessive but rather polar overdominant in which the phenotype is dependent upon receiving the mutant allele paternally and a normal allele maternally. This was a completely bizarre phenomenon because the gene is not on a sex chromosome.
In addition to the research questions, one of the coolest things to me about working in that lab was learning about Polymerase Chain Reaction, or PCR, a process by which you can take a single molecule of DNA and make billions of copies in just a few hours. I remember finding it so cool that all you really needed was some template DNA, building blocks of DNA, and an enzyme that could read the DNA and add the building blocks in the right order. I was also so intrigued by the crucial role that temperature plays in PCR – you essentially heat up and cool the reaction many times in order to make the specific stages of DNA amplification possible.
MS: What is the focus of your current research?
HN: The goal of my current research is to gain a better understanding of the folding of the genome in 3D space, specifically the ways in which the changes in folding patterns are implicated in disease. The genome folding ‘problem’ is fascinating to me because if you were to take the DNA from a single one of your cells and stretch it end to end, it would be about 2 meters long. Yet somehow, such a tremendously long molecule is able to compact and fold and fit inside the nucleus of a cell that is 5 – 10 micrometers in diameter. It turns out that the folding patterns of DNA are not random and in fact play a crucial role in proper maintenance of the genome as well as regulation of gene expression. I’m particularly interested in how the configuration of the genome changes between healthy and diseased cells.
TechGirlz is a non-profit that hosts and promotes many events for young women in tech. A core component of their work brings together women who are passionate about science and technology to share their knowledge and excitement with middle school-aged girls interested in these fields. Partnering with TechGirlz and two exciting start-ups, Benchling and Biomeme, we created a workshop that taught students the basics of DNA while also introducing them to what we think is most exciting in this field. Heidi—our resident genomics enthusiast—led the development of this workshop.
Megan Sperry: When did you first learn about genomics? What facts and ideas struck you as the most interesting?
Heidi Norton: I first learned about genomics as a high school student when I attended a Biotechnology Summer Academy and got to spend a week in a sheep genomics lab. I ended up working there for a couple of years throughout high school and got to learn about Callipyge, a fascinating heritable genetic condition in which the muscles of sheep’s buttocks hypertrophy, leading to really, really big butts. In addition to the very memorable phenotype, the coolest thing about this condition is its mode of inheritance – it was found to be neither dominant or recessive but rather polar overdominant in which the phenotype is dependent upon receiving the mutant allele paternally and a normal allele maternally. This was a completely bizarre phenomenon because the gene is not on a sex chromosome.
In addition to the research questions, one of the coolest things to me about working in that lab was learning about Polymerase Chain Reaction, or PCR, a process by which you can take a single molecule of DNA and make billions of copies in just a few hours. I remember finding it so cool that all you really needed was some template DNA, building blocks of DNA, and an enzyme that could read the DNA and add the building blocks in the right order. I was also so intrigued by the crucial role that temperature plays in PCR – you essentially heat up and cool the reaction many times in order to make the specific stages of DNA amplification possible.
MS: What is the focus of your current research?
HN: The goal of my current research is to gain a better understanding of the folding of the genome in 3D space, specifically the ways in which the changes in folding patterns are implicated in disease. The genome folding ‘problem’ is fascinating to me because if you were to take the DNA from a single one of your cells and stretch it end to end, it would be about 2 meters long. Yet somehow, such a tremendously long molecule is able to compact and fold and fit inside the nucleus of a cell that is 5 – 10 micrometers in diameter. It turns out that the folding patterns of DNA are not random and in fact play a crucial role in proper maintenance of the genome as well as regulation of gene expression. I’m particularly interested in how the configuration of the genome changes between healthy and diseased cells.
Maria demonstrating DNA collection.
MS: When you were thinking about developing a workshop, what concepts did you most want to convey to the students?
HN: I was really excited about teaching the students about PCR, a topic that got me hooked on biology as a 16-year-old. I specifically wanted them to understand that it is the amplification of the DNA that allows us to read and interpret it, and ultimately figure out how to hack it. I also wanted to convey to them how technological advances, sometimes simple and elegant ones, have allowed us to gain tremendous insight into biology.
HN: I was really excited about teaching the students about PCR, a topic that got me hooked on biology as a 16-year-old. I specifically wanted them to understand that it is the amplification of the DNA that allows us to read and interpret it, and ultimately figure out how to hack it. I also wanted to convey to them how technological advances, sometimes simple and elegant ones, have allowed us to gain tremendous insight into biology.
Megan and the students discussing the results of the experiment.
Dr. Maria Chacon-Heszele worked with us to incorporate Biomeme’s hand-held PCR machine into the workshop.
MS: What concepts did the students learn from interfacing with Biomeme’s product?
HN: One of the great things about Biomeme’s technology is how accessible it makes biology. In the workshop, we extracted DNA from sushi and then tested to see whether it was correctly labeled or not using real time PCR with primers designed to amplify species-specific barcodes. Biomeme’s hand-held PCR devices allowed the students to observe in real time how the DNA signal is amplified throughout the course of the reaction. They also learned how to interpret a positive and negative result. Something about actually holding the device in their own hands and seeing the read-out on the phone screen really drove home the point that biology and technology can be accessible to everyone.
Heidi recently wrote about using Benchling in her own research.
MS: What aspects of Benchling’s tools were included in the workshop? What can young students learn from using Benchling?
HN: I’ve found Benchling to be extremely useful in my own research over the past year, but through designing and executing this workshop I found that Benchling’s tools were great for teaching purposes as well. Benchling has a really great work flow that allows you to access the genome of a species of interest, search for a specific gene of interest, and design primers to amplify segments of that gene. We showed the students how we used Benchling to design the primers that allowed us to read the DNA ‘barcodes’, and then we set them loose to design primers to any gene of any species they were interested in. Some of the girls came up with really fascinating research questions they wanted to address and designed primers to amplify genes that would help them discover the answer. I was extremely impressed – they were asking questions like: Could congenital heart failure be due to a mutation in a gene that forms heart muscles?
MS: What was your favorite part of the workshop?
HN: My favorite part was seeing the students make connections between things they had learned in school, things that we were teaching them, and things that they had always wondered about. It was really cool to hear them brainstorm ideas of how DNA hacking could be used to learn more about the world around us and improve human health. Middle schoolers know what’s up!
MS: How can students learn about the genome at home? What are your favorite resources and tools?
HN: UCSC has a really great ‘genome browser’ that allows you to visualize specific genes or regions of the genome of interest. Not only can you look at the DNA sequences, but you can also see what genes are annotated and what epigenetic marks are present.
There is also a cool website that allows to look at maps of how the genome is folded in 3D space.
MS: What concepts did the students learn from interfacing with Biomeme’s product?
HN: One of the great things about Biomeme’s technology is how accessible it makes biology. In the workshop, we extracted DNA from sushi and then tested to see whether it was correctly labeled or not using real time PCR with primers designed to amplify species-specific barcodes. Biomeme’s hand-held PCR devices allowed the students to observe in real time how the DNA signal is amplified throughout the course of the reaction. They also learned how to interpret a positive and negative result. Something about actually holding the device in their own hands and seeing the read-out on the phone screen really drove home the point that biology and technology can be accessible to everyone.
Heidi recently wrote about using Benchling in her own research.
MS: What aspects of Benchling’s tools were included in the workshop? What can young students learn from using Benchling?
HN: I’ve found Benchling to be extremely useful in my own research over the past year, but through designing and executing this workshop I found that Benchling’s tools were great for teaching purposes as well. Benchling has a really great work flow that allows you to access the genome of a species of interest, search for a specific gene of interest, and design primers to amplify segments of that gene. We showed the students how we used Benchling to design the primers that allowed us to read the DNA ‘barcodes’, and then we set them loose to design primers to any gene of any species they were interested in. Some of the girls came up with really fascinating research questions they wanted to address and designed primers to amplify genes that would help them discover the answer. I was extremely impressed – they were asking questions like: Could congenital heart failure be due to a mutation in a gene that forms heart muscles?
MS: What was your favorite part of the workshop?
HN: My favorite part was seeing the students make connections between things they had learned in school, things that we were teaching them, and things that they had always wondered about. It was really cool to hear them brainstorm ideas of how DNA hacking could be used to learn more about the world around us and improve human health. Middle schoolers know what’s up!
MS: How can students learn about the genome at home? What are your favorite resources and tools?
HN: UCSC has a really great ‘genome browser’ that allows you to visualize specific genes or regions of the genome of interest. Not only can you look at the DNA sequences, but you can also see what genes are annotated and what epigenetic marks are present.
There is also a cool website that allows to look at maps of how the genome is folded in 3D space.
Learning how to use Benchling’s primer design.
MS: What is the future of genetics and epigenetics? What does the genomics space look like in 10 years? 2026?
HN: It’s hard for me to say where the field will be in ten years because things have been progressing extremely rapidly. One of the biggest current shifts that I see in genomics is a shift from focusing on ‘coding’ segments of the genome to ‘non-coding’ segments of the genome. Only 1.5% of the human genome codes for proteins, and it was once thought that all the rest was ‘junk DNA’. Famous last words, right? It turns out that there are so many functions that non-coding DNA performs and we are only beginning to understand and discover these functions. One fascinating function is that there are short sequences of DNA that are recognized by a specific protein that plays a role in folding DNA in 3D space. So the linear DNA sequence may help determine the 3D configuration of the genome! Recent advances in genome editing technologies (like CRISPR, which Megan mentioned), are allowing researchers to delete or mutate specific sequences of the genome in order to more rapidly determine their function, which is already proving to be extremely useful in better understanding both coding and non-coding segments of the DNA.
HN: It’s hard for me to say where the field will be in ten years because things have been progressing extremely rapidly. One of the biggest current shifts that I see in genomics is a shift from focusing on ‘coding’ segments of the genome to ‘non-coding’ segments of the genome. Only 1.5% of the human genome codes for proteins, and it was once thought that all the rest was ‘junk DNA’. Famous last words, right? It turns out that there are so many functions that non-coding DNA performs and we are only beginning to understand and discover these functions. One fascinating function is that there are short sequences of DNA that are recognized by a specific protein that plays a role in folding DNA in 3D space. So the linear DNA sequence may help determine the 3D configuration of the genome! Recent advances in genome editing technologies (like CRISPR, which Megan mentioned), are allowing researchers to delete or mutate specific sequences of the genome in order to more rapidly determine their function, which is already proving to be extremely useful in better understanding both coding and non-coding segments of the DNA.
From left to right, Heidi, Maria, and Megan.
