# A Comprehensive Resource for Manipulating the Drosophila Genome

> **NIH NIH R24** · BAYLOR COLLEGE OF MEDICINE · 2022 · $802,136

## 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 ~22,000 (located in/near 13,000 genes) to be selected and deposited in the Bloomington Drosophila
Stock Center. More than 750,000 GDP cultures have been distributed to thousands of labs nationally and
internationally, facilitating the analysis of thousands of genes. The features of the TEs developed by the
GDP, particularly the MiMIC TE, greatly enhance their value as they allow characterization of gene
expression, protein distribution, tissue specific knock down, isolation of interacting proteins, assessment of
the function of homologues of other species and other sophisticated, state-of-the-art manipulations. The
flexibility to swap any DNA cassette into existing MiMIC TE sites provides a genetic toolkit that is unrivaled,
greatly advancing the field of functional genomics and impacting our understanding of gene function across
species.
 During the proposed budget period, the GDP will provide tools to analyze gene function that will
constitute a new resource not only to tackle basic biological questions but also medical questions aiding with
the discovery and study of new human diseases and their underlying mechanisms. A critical prerequisite for
modeling disease in Drosophila is the ability to express each of the 9,000 evolutionarily conserved human
genes in the endogenous expression pattern of their fly ortholog. 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 UAS-cDNA of a
fly or human homolog, frequently rescuing the mutant phenotype and allowing disease modeling. Here, we
propose to expand the tagging of most genes that can be tagged with this approach. We have also
developed a new strategy to permit replacement of all genes that do not have suitable introns for T2A-GAL4
integration, which constitute about 45% of all fly genes. This method exchanges the gene's entire coding
regions with a Kozak consensus sequence followed by GAL4. We propose to target 2,300 currently untagged
Drosophila genes using these two strategies depending on the structure of the locus and the nature of the
cassette to be inserted. The vast majority of the genes will be tagged with GAL4 because it permits numerous
elegant applications. The resulting lines will be characterized genetically and molecularly and the expression
pattern of the genes will be documented in third instar larval brains. The generation and distribution of these
reagents is highly appreciated by the Drosophila community as shown by the many letters of support from
leaders in the fly community.

## Key facts

- **NIH application ID:** 10437006
- **Project number:** 5R24OD031447-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** HUGO J BELLEN
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $802,136
- **Award type:** 5
- **Project period:** 2021-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437006

## Citation

> US National Institutes of Health, RePORTER application 10437006, A Comprehensive Resource for Manipulating the Drosophila Genome (5R24OD031447-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10437006. Licensed CC0.

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