A crispr-based toolkit for investigating hair cell transcription factors in inner ear organoids
Active Project Grant Awarded Last action
- Award ID
- R00DC021984
- Recipient
-
Merrimack College UEI QHNZEGD6NWL5
- Awarding agency
-
National Institute on Deafness and Other Communincation Disorders
National Institutes of Health, Department of Health and Human Services
- Obligated
- $497,878
Award facts
- Assistance listing
- 93.173 Research Related to Deafness and Communication Disorders
- Completion date 38% complete
- Place of performance
- North Andover, MA 01845, USA
Award details come from USAspending.gov.
Description
- Abstract
- Hair cells (HCS) are the specialized sensory cells of the inner ear that play a crucial role in transmitting environmental information, such as sound and motion, to the brain. In adult mammals, HCS cannot regenerate naturally. Therefore, a large effort has been made to understand the normal development of auditory and vestibular HCS, so that effective regenerative therapies can be established. Technological advancements in studying transcriptional control have provided valuable insights into the roles of different transcription factors (TFS) such as ATOH1, POU4F3, GFI1, INSM1, TBX2, and IKZF2 in the development of HCS. However, the application of certain tools, such as crispr-mediated gene activation and inhibition, for studying HC development has been limited by the complicated use of animal models. Recently, a highly scalable protocol was developed to guide mouse embryonic stem cells (mescs) towards inner ear sensory cells in vitro. Over a span of 2-3 weeks, these inner ear organoids produce sensory epithelia-like structures complete with mechanosensitive HCS and underlying supporting cells. The development of this inner ear organoid model facilitates the progress of cell-based assays for studying HC-specific development and testing potential treatments for sensory cell loss. In this proposal, i aim to utilize the inner ear organoid model to investigate the transcriptional control of HC development in vitro. To achieve this, i plan to: i. Define the TFS involved in in vitro inner ear organoid HC development compared to in vivo HC development. II. Generate a versatile toolkit of mesc lines designed for inducible and reversible crispr-mediated gene activation and inhibition. III. Utilize this toolkit to systematically investigate the roles of candidate TFS in organoid HCS through crispr-mediated knockdown and activation, followed by multi-omic analyses. Successful completion of this project will not only uncover additional TFS essential for HC development but will also provide a valuable resource for fellow inner ear researchers seeking to manipulate the expression of genes of interest within inner ear organoid cell types.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $248,878 | |
| Original award | $249,000 |
Quick answers
Who received award R00DC021984?
R00DC021984 was awarded to Merrimack College by National Institute on Deafness and Other Communincation Disorders (National Institutes of Health) on September 2, 2025.
How much is award R00DC021984 worth?
$497,878 has been obligated on R00DC021984.
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