For more than 100 years, the fruit fly Drosophila melanogaster has been used extensively as a versatile model organism in genetics, developmental biology and other areas of biomedical research. We had the opportunity to speak with Kristin Klueg, Associate Director at The Drosophila Genomics Resource Center (DGRC) who shares fascinating insights into the advantages of using Drosophila and key research advances made.
Please could you share with us a bit of background to the DGRC. When was it founded and what is the role of the Centre?
The concept came about in the early 2000s. The Drosophila (fruit fly) community has been around for a long time, with its own board of scientists to help guide what the fly community needs and wants for their research. The DGRC started at Indiana University with a couple of faculty member members who were already very much involved in the Drosophila community. They started meeting with other fly community members and the Board to discuss these issues. It became apparent that there were a lot of genetic resources that were being developed that researchers were interested in using, but it was difficult for the labs to make those resources easily available to the community. Many cDNA libraries were being made and it was up to each individual lab that created those clones to distribute to the Drosophila community, which can be cumbersome and time consuming.
Three faculty members at Indiana University wrote a grant to the National Institute of Health, one of our big funding agencies in the US, requesting funding for a resource center; one that would serve three-fold: 1) to act as a centralized place to collect molecular and cellular resources for Drosophila, 2) to help archive and then redistribute those resources to community members as needed, and 3) to explore emerging technologies applicable to Drosophila research. It was proposed that such a resource center would take the burden off individual labs and scientists and created a centralized place for shared resources.
The grant proposed that the newly established resource center would collect cDNA and vectors that were commonly used in Drosophila. At that time, it was known that there were about 5000 to 10,000 cDNAs that would be most desirable by the community. It was estimated that there might be up to 100 Drosophila cell lines but back then but it wasn’t really clear how many there were. There were approximately 10 cell lines that were well known, and a few other unpublished ones that people had heard about in other countries but little was known about them . And at that time, there was an emerging technology, referred to as “microarrays”, which was part of the grant as well.
The grant was funded in 2003 and the newly formed DGRC began collecting the known cDNA clones and vectors; it also searched for cell lines that that people might want and started developing the microarray tools for Drosophila. I, along with two other lead scientists, headed up the subgroups within the DGRC. I oversaw the cDNA and vectors group, Dr. Lucy Cherbas was in charge of the cell lines, and Dr. Justen Andrews headed up the microarray group. We opened to the scientific community in 2004. At the time, we estimated that there would be 5000 to 10,000 cDNAs that we would make available and up to 100 cell lines.
Over the course of the last 17 years things have changed significantly. Technology has skyrocketed in ways we never anticipated. We now house over 1.5 million Drosophila cDNA clones and have several hundred cell lines. In addition, new cell lines are being a generated now by our lab and other labs. We have moved away from the microarray technology and now work on emerging technologies like CRISPR-Cas9.
We have evolved in ways we never imagined and the reason we have been so successful is because we implemented an emerging technology back then for the cDNA clones – one that has allowed us to house a large number of DNA clones in a small amount of space at room temperature for decades. This technology utilizes a specialized type of paper called “FTA Whatman” paper, a more advanced type of paper that was originally developed for forensics. It’s about the size of a business card and holds large amounts of DNA. When someone wants a clone, we pull a given clone card off the shelf, take a little piece off of it and ship it. It lasts for decades, making it a great way to store DNA.
How would you explain your profession to a layperson?
I always describe it as a combination of two things: 1) we are kind of like a library or an archive. We bring these things in to store and archive them, and 2) we are also like an Amazon store for scientists; we have a website, with a shopping cart and biologists can choose what resources they want online, put it in their shopping cart and checkout.
Why is Drosophila used in genetics?
Prior to DNA being discovered, Drosophila was already recognized as a really powerful genetic organism over 100 years ago. It had been (and still is) used genetically because it has a quick life cycle and has what is called polytene chromosomes, which are these big puffy chromosomes. People could localize certain genetic traits to different parts of those chromosomes. It already lent itself to an easy genetic organism. Over the years, it became known that you could do a lot with this organism quickly. People do not generally care if you kill a fruit fly (whereas they might care if you kill a mouse or other vertebrate) so you can do genetic mutations and genetic work in the fruit fly and nobody’s going to bat an eye if you kill 1000s of flies in the course of your research. This make it a very amenable organism for genetic studies. It was actually the organism chosen to test the principle of genome sequencing back in early 2000. Back then it really wasn’t known if that was possible, the techniques were very different at that time, so Drosophila was used as that test for genome sequencing. It was a proof of principle. Drosophila continues to be used as a very powerful genetic organism. Approximately 75% of the genes implicated in human disease are also found in Drosophila. That is one of the reasons why Drosophila continues to be studied: it is a model organism for human disease.
What are the benefits to using Drosophila over vertebrate models?
The benefits include the short life cycle, you can make genetic crosses, you can acquire progeny very quickly, and you can make mutations very easily. It is inexpensive to rear in a laboratory, where as a vertebrate system has a slower genetic life cycle so it takes much longer to do crosses. You can do many crosses in a year with Drosophila, whereas you might only get a few crosses in a year in a vertebrate system. And, it is more expensive to raise mice or zebrafish in a laboratory.
What are some of the fascinating advances that research using Drosophila has contributed?
The genome sequencing was a big thing, being able to sequence the genome and prove that one could do high throughput sequencing using Drosophila. Since then, the fact that it has been a model organism for human disease has provided a number of fascinating, insights into various diseases.
Fruit flies can essentially get cancer, Alzheimer’s, Parkinson’s, epilepsy, obesity, heart disease and other diseases just like humans. Being able to study those diseases in a fruit fly and learn a lot quickly and then being able to apply that to the vertebrate and human systems really gives powerful insight to human disease. Now with the discovery of the CRISPR-Cas9 (gene editing), Drosophila has really been very powerful in that aspect as well, drilling into how CRISPR-Cas9 can be used to edit genes to study human disease is a significant advancement.
Which trends and technologies do you find to be particularly exciting these days in your field?
The CRISPR-Cas9 is definitely at the forefront; it is popular and holds a lot of promise -it’s one of the things that many scientists are working on right now. So using the CRISPR-Cas9 gene-editing tool is probably the most promising new technology that we have.
There are now researchers who are using Drosophila to study rare human diseases, a sort of “personal therapeutics”. A company called Vivan Therapeutics (formally My Personal Therapeutics) uses Drosophila to screen drugs for various human diseases. Let’s say you have been diagnosed with a really rare cancer, the big drug companies are not going to spend tons of money to research your rare cancer, it’s not in their corporate makeup to do that. But if you use Drosophila and look at those genes that are very similar and you start mutating them, then testing drugs, doing a drug screen in Drosophila then you can, in a couple of months, screen through hundreds of drugs and see which of those might be potentially useful for fighting a rare cancer or human disease. I think that is going to become an incredibly powerful tool if it continues to be worked on and developed. There are companies now, small startups that are doing this with people who have been diagnosed with a rare disease; they are using Drosophila to try and find those drugs or those drug combinations that might work best for them.
What can we expect to see in the future of your industry, any new developments that you can share with us?
The CRISPR-Cas9 is still continuing to be worked on. Within our group, we have a small research development group using CRISPR-Cas9 and creating tissue culture lines in Drosophila and related tools for other community members to use, there are other labs that are doing this as well. That continues to be a very promising area that will flourish. And using Drosophila to screen drugs to combat rare human diseases is remarkable.
And, interestingly, I attended a conference two years ago and there was a group outside the U.S. looking at Drosophila as a potential food source, exploring the potential for high protein as a way to address concerns about food insecurity.
