Experimenting in an Open Source lab: from CRISPR to Cats

Posted by Guest Blogger on Jul 23, 2015 10:30:00 AM


The following post was contributed by Derek Jacoby from Makerspace Victoria, CA

Over the decades science has become increasingly restricted to academic and industrial labs, but recently there has been a counter movement by the public to access basic equipment and to become involved in developing tools and solutions to research problems. This movement calls itself the Open Science movement and is part of a bigger movement in a variety of research sectors to provide open source technologies and spaces where interested parties can do research. This interest manifested itself in the creation of Hackerspaces and Makerspaces back in 2007, which function as centres for peer learning and knowledge sharing, in the form of workshops, presentations, and lectures. There are currently around 1,000 active makerspaces around the world. Hackerspaces.org maintains a list of active spaces near you.

Members of the Victoria Makerspace

Learning about C. elegans with the OpenWorm Project

One such space is the Victoria Makerspace in Canada, which I belong to. The team at the Victoria Makerspace is composed of computer scientists, engineers, and biologists working together on a variety of projects including the OpenWorm project. The main goal of OpenWorm is to simulate C. elegans as a computer model. When I first heard about it, I got excited from a computer scientist perspective. But, the more I thought about it, the more I realized that it cuts across multiple disciplines, which really epitomizes what the makerspace is. The computer scientists can get involved in modelling, the electronics folks can build a robot worm on top of that model, and the biologists can get involved a in variety of aspects from the molecular biology to learning how to grow and care for the worms.

As an example of one of the problems we work collaboratively to solve, we want to focus our research on worm locomotion, but our worms are constantly moving so we need good ways to monitor and track them. We have a number of microscopes, including an automated microscope but we need to develop the manual skills at the regular microscope, and the scripting skills at the automated microscope  to keep our worms and our research goals in focus. Developing these skills relies upon biologists and computer scientists learning and communicating with one another.

 

Microscopy of C. elegans

 

Currently our main focus is coding the molecular biology of the worm into a computer model that recapitulates how molecular biology impacts worm locomotion. Our most recent models of C. elegans molecular biology are based on the standard worm genome. While C. elegans are often thought of as simple organisms , they have many levels of complexity, especially when trying to explore the links between genetics and anatomy, which are not yet fully understood. We attempt to deconstruct and understand this complexity using existing C. elegans mutants. For instance, we use a mutant known as CX51 that exhibits motor defects above 25 degrees. Computer scientists and biologists work together to compare the predictions about the effects this mutation has on locomotion in our computer model to the effects of this mutation in the real mutant worm. Like many academic labs, we have the capability to study many different mutants because the Caenorhabditis Genetics Center (CGC) at the University of Minnesota has declared our makerspace an educational institution meaning that we can obtain known mutants at $7.00 a strain. Makerspaces like ours can also make accounts with  Addgene. We now have the incredible CRISPR/cas9 tools at our disposal to to modify the worm genome and make additional mutations in our worms.  We are on the lookout for genome modifications that do not exist in the CGC library but that would be useful to our model  so that we can use CRISPR/cas9 to build the mutants, analyse their motor behaviour, and ultimately submit our new strains back to the CGC for other researchers to use. Although we haven’t yet made our final target decisions, we intend to focus on motor neuron knockouts so that we can perturb factors related to worm motion.

 

C. elegans model

Working on the Cat Microbiome Project

Another project we are working with is the cat microbiome project. This is a project looking at the makeup of the bacterial species in the gut of the domesticated housecat, and seeing how that makeup differs from that of wild cats with the goal of optimizing the health of domesticated cats and learning about feline microbiomes. One of the aspects of this project that makes it ideal for makerspaces is the data is freely available, and the collection of samples and sequencing is being organized and funded by someone else (KittyBiome has been incorporated as a non-profit entity and so far most of their funding has come from kickstarter and fundrazr projects). This allows the project to be open to a wider group of people. This is a perfect starter project for our computer scientists, many of whom are interested in biology but don’t really know how to start applying their skills to it. The Kittybiome project gives them access to rich and complex microbiome data for analysis. And, well, cats... everyone knows the internet loves cats! This is mostly a project to get our computer folks at the makerspace comfortable with next-generation sequencing data and the bioinformatics pipeline. It’s possible that we’ll find something interesting and contribute it back to the kittybiome project, but the primary goal is learning in this case.

Makerspace in Victoria

Funding Makerspaces

One of the main challenges when starting a new project at a makerspace is finding the financial resources to pursue it. Since makerspaces are generally funded on a membership model - everyone contributes each month - with only occasional supplementation with grant funds, money is always tight. Of course, unlike your traditional biology lab, we have members with a wealth of skills to help do science on the cheap using equipment that would otherwise be discarded. For instance, the centrifuge in the picture had a broken controller and would not spin. It was going to cost far more than it was worth to repair the controller and a new replacement was not possible, but one of our members took an Arduino microcontroller and a motor controller and made it spin again! 

We’ve also learned to be resourceful and to repurpose old equipment for new uses. We’ll probably never use the Illumina GAIIx we recently acquired  for sequencing again - it’s too inefficient and the reagents are too expensive to make it practical - but we have members looking at how to re-use it as a platform for monitoring homemade microfluidic chips using the fantastic optics and fluidics platform it contains. Biotech equipment becomes obsolete amazingly fast, but with a wide range of skills among our members we’ve managed to learn a lot and cobble together quite a diverse array of capabilities. So don’t throw old equipment away until you ask your local makerspace if they want to hack new life into it!

If you’re in the Victoria area, please stop by. And if not, I suspect you can find a makerspace somewhere near you. The place to start looking for your local space is the Hackerspace website. Markerspaces differ depending on the interests of their community, and biology is not yet common, but it’s growing! The common factor in all makerspaces is a passion for learning and having fun with technology, so feel free to contact your local space and get involved!


Derek Jacoby

Derek Jacoby is a PhD student at the University of Victoria. After a decade at Microsoft Research working on speech recognition, he returned to school to merge his interests in biology and computing. In 2009, he founded a team at UVic to compete in iGem, an MIT-sponsored synthetic biology competition. In 2010, he founded makerspace.ca, Victoria’s first hackerspace which now offers members and the public cheap access to personal manufacturing tools – a 3D printer, a laser cutter, woodworking tools, and a metalshop. After two summers in Silicon Valley as a student and then instructor at Singularity University at NASA Ames, and an instructor at Biocurious.org, Derek is bringing cutting edge technologies to Victoria, BC.

Follow Derek on Twitter @derekja and visit his website: biobit.ca

 Resources

Hackerspace Website

https://wiki.hackerspaces.org/Hackerspaces

OpenWorm Project Website:

http://www.openworm.org/

Cat Microbiome Project Website:

http://www.kittybiome.com/

Find C. elegans plasmids at Addgene!

Plan Your Next CRISPR Experiment, Click to Start Now at Addgene

 



Topics: Scientific Sharing

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