Neuroscience research just got a little easier, thanks to the release of tens of thousands of images of fruit fly brain neurons created by Janelia’s FlyLight project team.
Over eight years, the FlyLight Project team and their collaborators dissected, labeled and imaged the neurons of more than 74,000 fruit fly brains, obtained from more than 5,000 different genetically modified fly strains.
Now, these images are freely available, allowing scientists to quickly and easily find the neurons they need to test theories about how the nervous system works.
The release of images February 23 in the magazine eLife is the culmination of many efforts and contributions from dozens of Janelians, starting in 2012. It demonstrates Janelia’s commitment to creating free resources useful for the entire scientific community. It also underscores the mission of the research campus to undertake projects that cannot be accomplished in a traditional research environment where these long-term efforts are often not funded or incentivized.
“It’s a great resource for the community,” says Geoffrey Meissner, who was the project scientist for FlyLight and first author of the new paper in eLife. “It’s very clear in Janelia’s mission, and it highlights Project Teams as an idea — to do these big things beyond the scale of what a lab could reasonably do — and really emphasizes the open science aspect of its goals. Janelia. We want you to go the extra mile to make it available to everyone, to make it easy, to make it more complete.”
Using flies for neuroscience research
The fruit fly Drosophila melanogaster is a key element of neuroscience research. Scientists use genetically engineered fruit flies to target the expression of certain neurons, allowing researchers to understand which brain cells control certain behaviors.
Scientists were using fruit flies to understand the nervous system when Janelia opened in 2006, but researchers didn’t have tools precise enough to implicate individual neurons.
This led Janelia to create the FlyLight project team, which set out to create genetically engineered flies that scientists could use to inhabit specific neurons with greater precision. In 2012, Janelia released the first generation of these fly strains, the GAL4 Generation 1 driver lines, along with microscope images showing where specific neurons are located in the brain.
But Generation 1 lines were still too imprecise for some neuroscience research. So FlyLight developed fruit fly strains from these GAL4 lines using the Split-GAL4 approach that allowed the scientists to identify individual neurons or individual cell types in the fly brain.
Since they were developed, the Split-GAL4 lines and the Split-GAL4 system have been used by researchers around the world. But figuring out how to generate a specific Split-GAL4 needed for an experiment can be difficult. To do this, the researchers must first label the neurons of interest in the GAL4 lines — a task that can be difficult for a single researcher.
To help, the FlyLight team used a technique called MultiColor FlpOut (MCFO), developed by Aljoscha Nern, a senior scientist in the Rubin Lab, to label individual neurons in GAL4 Generation 1 driver lines. Creating the more than 70,000 of detailed images now available required over 11 years of imaging time on 8 confocal microscopes.
Janelia’s Scientific Computing team created a freely available tool called NeuronBridge that allows researchers to search the MCFO-labeled images, along with other light and electron microscopy data, to locate the neurons of interest. It also allows researchers to predict the Split-GAL4 combinations they will need for their experiments.
“FlyLight made a lot of images, but without our close collaboration with Scientific Computing, it would have been just terabytes of data on a hard drive that no one could do anything with. They were instrumental in making it usable for people.” , says. Meissner, who is now senior director of Project Pipeline Support, which continues to provide FlyLight pipelines to Janelia Labs.
A global resource
The publication on eLife marks the official release of the images, but neuroscientists around the world have already taken advantage of the data since its initial release in 2020.
The latest effort builds on Janelia’s reputation for developing tools that facilitate fruit fly research.
“The general feeling is that for anyone doing fly neuroscience who wants to target a neuron and learn something about it, the best way is to use the FlyLight-characterized GAL4 lines,” says Meissner.