# A Comprehensive Resource for Manipulating the Drosophila Genome

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $646,303

## Abstract

PROJECT SUMMARY
 The Drosophila Gene Disruption Project (GDP), since its foundation in 2000, has produced a large,
publicly available library of individual, sequence-mapped transposable element (TE) insertions that have become
an essential resource for fly research. Generating and sequencing 180,000 TEs allowed the most useful ~16,000
(located in/near 13,000 genes) to be selected and deposited in the Bloomington Drosophila Stock Center, where
they comprise 25%-30% of all stocks. >700,000 GDP cultures have been distributed to thousands of labs
nationally and internationally, facilitating the analysis of thousands of genes. The features of the TEs newly
developed by GDP greatly enhance their value as they allow characterization of gene expression, protein
distribution, tissue specific knock down, isolation of interacting proteins, assessing function of homologues of
other species and other sophisticated, state of the art manipulations. GDP’s MiMIC TEs contain ϕC31 target
sites that permit in vivo genetic swapping of the cassette. The flexibility to swap cassettes into existing MiMIC
sites provides a genetic toolkit that is unrivaled in other species, greatly advancing the field of functional
genomics and impacting our understanding of gene function across species.
 During the proposed budget period, GDP will provide tools that will be used to analyze gene function and
constitute a new resource for medicine, aiding with the discovery and study of new human diseases and the
underlying mechanisms. A critical prerequisite for modeling disease in Drosophila is the ability to express each
of the 9,000 homologous human genes in the normal fly gene expression pattern. This can currently be achieved
by using MiMIC and the SA-T2A-GAL4-polyA cassette (T2A-GAL4). When inserted in introns between two
coding exons, this cassette is highly mutagenic and produces a GAL4 that can be used to drive the cDNA of a
fly or human homolog, frequently rescuing the mutant phenotype and allowing disease modeling. The major
focus of the GDP is to expand the number of genes with an inserted T2A-GAL4, especially those with recognized
human homologs. To enable tagging of all genes, we developed new genetic strategies, one utilizing CRISPR
(CRIMIC) to insert T2A-GAL4 in introns and two that replace the coding regions of genes with GAL4. Here we
propose to tag 3,000 Drosophila genes using these strategies depending on the structure of the locus and the
nature of the cassette that we wish to insert. The vast majority of genes will be tagged with GAL4 because it
permits numerous applications including disease modeling. The resulting lines will be characterized genetically
and molecularly and the expression pattern of the genes will be documented in third instar larval and adult brains.
Progress will be delayed or denied if it is left to individual laboratories to generate the technically demanding
strain construction, rather than having it carried out efficiently by GDP on a large sc...

## Key facts

- **NIH application ID:** 9995497
- **Project number:** 5R01GM067858-18
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** HUGO J BELLEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $646,303
- **Award type:** 5
- **Project period:** 2003-05-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9995497

## Citation

> US National Institutes of Health, RePORTER application 9995497, A Comprehensive Resource for Manipulating the Drosophila Genome (5R01GM067858-18). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9995497. Licensed CC0.

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