# A novel Drosophila platform for sequential genetic manipulations in vivo

> **NIH NIH R21** · FLORIDA STATE UNIVERSITY · 2021 · $231,000

## Abstract

PROJECT SUMMARY
 The ability to perform sophisticated genetic manipulations and large-scale exploratory studies is a key
strength of Drosophila as a model system. This proposal leverages this strength and pushes the limits of
Drosophila genetics to establish a novel, innovative and ambitious platform that allows sequential introduction of
genetic manipulations —each coupled with a different fluorescent protein— into individual cells. My laboratory is
interested in using this platform to build and study tumors in the adult Drosophila intestine composed of
genetically heterogeneous cell populations with distinct mutation profiles (i.e. subclones). We have previously
used tumor sequence data as blueprints to build several colorectal cancer models by genetically manipulating
Drosophila orthologs of human cancer driver genes in the adult fly intestine. We now seek to expand these efforts
to building new cancer models that reflect tumor subclonal architectures identified by sequencing and
computational studies.
 Tumors arise by sequential accumulation of genomic alterations in cancer driver genes. Consequently, most
solid tumors are composed of subclones with distinct mutation profiles in constant competition for limited space
and resources. Therapy often alters subclonal dynamics by introducing additional selective pressures, eventually
leading to the expansion of resistant subclones and therapy failure. Building subclonal tumors is a technically
challenging problem that requires sophisticated genetic manipulations and represents an important area of
unmet medical need. Drosophila is a useful cancer model that captures several key hallmarks of human tumors,
including colorectal cancer. The adult Drosophila intestine is a well characterized tissue with multipotent intestinal
stem cells where signaling pathways altered in colon tumors are remarkably conserved and well characterized.
The platform proposed here, combined with practical advantages of Drosophila, provides a unique opportunity
to generate tumors with diverse subclonal architectures observed in human tumors. If successful, this technology
will complement mammalian cancer models by providing an experimental platform to functionally explore yet
another layer of complexity of human tumor genome landscapes revealed by big cancer data. We also hope to
use this platform to explore the impact of altering the order of cancer driving genomic alterations on
tumorigenesis and the potential of different cell types of the intestine as tumor cells of origin.
 The platform proposed here is a flexible technology that can easily be combined with other genetic tools to
generate populations of cells carrying different genetic manipulations barcoded with unique fluorescent protein
combinations in any tissue of interest. If successful, it could open up promising opportunities in other research
areas including developmental biology, stem cell biology and neuroscience by providing a platform to explore
mechanisms o...

## Key facts

- **NIH application ID:** 10193543
- **Project number:** 1R21GM141734-01
- **Recipient organization:** FLORIDA STATE UNIVERSITY
- **Principal Investigator:** Erdem Bangi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,000
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10193543

## Citation

> US National Institutes of Health, RePORTER application 10193543, A novel Drosophila platform for sequential genetic manipulations in vivo (1R21GM141734-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10193543. Licensed CC0.

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