Connecting biological mechanisms across spatial scales requires experimental tools that allow for investigation from molecules to entire organisms. Cell and developmental biologists routinely use imaging tools such as electron and light microscopy to investigate single molecules to individual tissues and organs. However, despite Drosophila's popularity for probing many molecular mechanisms using these methods, techniques that permit visualization of entire intact animals at later developmental stages have not been widely utilized.
We developed a method that permits whole animal imaging of Drosophila at high resolution. Micro-computed Tomography (u-CT) is an X-ray based technique that allows for non-destructive imaging of flies at any developmental stage. It requires no dissections, maintains the native orientation of all organs within the body and provides accurate 3D information of those structures for morphometric analysis. We have used this technique to precisely measure adult brain size in our fly microcephaly models, describe mechanisms of pupal development at incredible detail, and identify novel mutant phenotypes at all stages of fly development.
With u-CT's incorporation into a pipeline that maximizes the strengths of each imaging platform (electron microscopy, light microscopy, u-CT), the entire biological spatial hierarchy from molecules to entire organisms can now be investigated in high resolution. This permits a near-complete understanding of a given biological process, making it a powerful approach for investigating gene function.
We are continuing to develop u-CT methods for flies that push the resolution limit of the technique, identify novel or overlooked developmental phenotypes, and showcase it's usefulness to researchers in the Drosophila community through collaborations (contact me if interested). We have also begun using artificial intelligence to automate image processing in order to extract as much biological information as possible from our u-CT images. Once this bottleneck is addressed, u-CT can be incorporated into a larger pipeline aimed at unbiased phenotype identification, particularly in fly models of human disease.
We developed a method that permits whole animal imaging of Drosophila at high resolution. Micro-computed Tomography (u-CT) is an X-ray based technique that allows for non-destructive imaging of flies at any developmental stage. It requires no dissections, maintains the native orientation of all organs within the body and provides accurate 3D information of those structures for morphometric analysis. We have used this technique to precisely measure adult brain size in our fly microcephaly models, describe mechanisms of pupal development at incredible detail, and identify novel mutant phenotypes at all stages of fly development.
With u-CT's incorporation into a pipeline that maximizes the strengths of each imaging platform (electron microscopy, light microscopy, u-CT), the entire biological spatial hierarchy from molecules to entire organisms can now be investigated in high resolution. This permits a near-complete understanding of a given biological process, making it a powerful approach for investigating gene function.
We are continuing to develop u-CT methods for flies that push the resolution limit of the technique, identify novel or overlooked developmental phenotypes, and showcase it's usefulness to researchers in the Drosophila community through collaborations (contact me if interested). We have also begun using artificial intelligence to automate image processing in order to extract as much biological information as possible from our u-CT images. Once this bottleneck is addressed, u-CT can be incorporated into a larger pipeline aimed at unbiased phenotype identification, particularly in fly models of human disease.
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3D u-CT rendering of a third instar larvae. Individual organs are highlighted by color.
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3D u-CT rendering of a WT pupa and spc105r RNAi mutant. Brain is rendered in blue, ventral nerve cord in red and 'head remnant' in yellow. Mutants fail to develop head structures, but the brain develops ectopically in the thorax.
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3D u-CT rendering of an adult, highlighting the various thorax muscle groups by color.