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.

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. 

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. 

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 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. 

​by Heidi Norton
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Ever since my sophomore year of college when I got my very own hard-bound, very official looking lab notebook, I’ve enjoyed the process of keeping a lab notebook (maybe a little too much...). Print-outs of every gel I ran would be lovingly taped into the pages; so would protocols with dozens and dozens of steps. I would draw schematics of my experiments, draw big smiley faces on days my experiments worked, and sad emojis when things failed. Keeping up this methodical notebook took time. No joke, I must have spent at least two hours a week cutting and taping. And oh man, can I go through a paper lab notebook quickly!
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So far in my research career, I’ve spent significant time in 5 research labs (oddly enough, four of these begin in a C: Cockett, Cochran, Chen, and Cremins!) and have had to leave my lovely lab notebooks behind. I kept adequate digital copies of protocols from all the labs I’ve been in, but if I ever want to take a walk down memory lane and look at gel images of yester-year, I’m out of luck. Even more important than science nostalgia, if I ever want to find a protocol that I used a few years ago to replicate an experiment, I have to comb through pages and pages in my dozens of paper notebooks.

I’ve been interested in the concept of a digital lab notebook for a while exactly because of this issue – I want to be able to access my lab notebook from my current lab and previous labs from anywhere and easily find a lab notebook entry or protocol in seconds. I’d known fellow graduate students who have used digital note-taking applications as a lab notebook and I had toyed with the idea a few times. Ultimately, I was concerned about how easily some notes could be deleted and how difficult it would be for other lab members to access my lab notebook.

I first heard about Benchling at a happy hour that they sponsored for grad students in my department. They passed out free t-shirts with their cool logos and made a pitch for their new concept for a digital lab notebook that streamlines the scientific collaboration process through easy search-ability and seamless integration with cloning tools. As soon as I got back to my lab after the happy hour, I set up an account and was instantly excited. (I know this might sound too enthusiastic, especially because this is a sponsored post – but I’m not exaggerating here. It was exactly what I was looking for!). I noticed that digital back-ups of my notebook entries were automatically saved regularly and that I could easily share my whole notebook or individual entries with my labmates.

The first thing that excited me about Benchling is its calendar lab notebook view. I can create a multi-day lab notebook entry for a given project, but also have another multi-day lab notebook entry spanning the same days for a different project. This works great for me when I have multiple projects that I work on in a given week, the details of which easily become disorganized in a paper lab notebook. I can easily click on my calendar to view which experiments I completed that day, but can also click through consecutive entries for a given project. And, I was excited to find the feature that I can export my lab notebook entries in chronological order spanning all projects and print them into a hard copy lab notebook to have as a back-up.

Once I realized how much utility Benchling could have in my research, I started telling my labmates about it. We loved how easily we could share protocols and view each others’ plasmid designs. Soon, enough of us were using it that we did a lab-wide trial run.
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Around the same time, I started transitioning from entirely wet-lab (experiments at the bench) to a substantial amount of dry-lab (writing code to analyze and model our data). I’m finding that Benchling is a great way for me to keep track of the directory I’m working from for a given task, what the goals/problems I’m trying to solve are, and relevant snippets of code. This would be literally impossible with a paper lab notebook (ok, not totally impossible, but so so tedious).
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​Another huge upside for me is that it is 1,000x easier to find a labmate’s protocol by clicking on their Benchling notebook and searching ‘Neural Stem Cell plate coating’ than by searching for 20 minutes for the hard copy lab notebook and spending another 20 minutes flipping through the pages to maybe find the right entry with difficult-to-read handwriting.
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​In short, I love the organizational capabilities of Benchling because it helps me keep track of multiple projects in a coherent manner, allows me to access my lab notebook from anywhere, helps me easily search through my colleagues’ lab notebook entries (without the risk of me modifying their entries), and offers a solution for keeping a record of computational lab work.

Stay tuned for Benchling’s re-design that has some awesome new organizational tools. One of the things that I’m interested in is ability to perform sample inventory, which looks like it will have awesome utility especially for tracking cell lines.
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In case you needed any additional convincing, Benchling’s cloning tools are so cool that they deserve their own post, but I’ll give you a teaser. In the 5 minutes between writing paragraphs as I was thinking about what I wanted to say, I downloaded the gene in the specific assembly of the murine genome I want to edit, designed guide RNAs for the CRISPR nickase system to edit my locus of interest, selected the guide pair with the highest on-target score and lowest off-target score that fit my overhang criteria, and assembled the guide RNAs into my lentiviral puro-selection plasmid of interest – all without leaving the Benchling interface.

If you’ve ever wondered about using a digital notebook, or if you never even knew you needed a digital lab notebook in your life but now you’re curious, check out Benchling here!
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