Mechanisms and developmental functions of cytoplasmic flows in early embryogenesis
Ended Project Grant Awarded Last action
- Award ID
- R01GM136763
- Recipient
-
Duke University UEI TP7EK8DZV6N5
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $2,759,785
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Funding
-
- $2,458,528.89 Federal
- $301,256.00 Non-federal
- Place of performance
- Durham, NC 27705, USA
Award details come from USAspending.gov.
Description
- Abstract
- The integration of biochemical and mechanical signals is an important and ubiquitous feature of biological systems. During embryonic development, this integration is required for complex tissue organization and function. We have recently shown that during the early, pre-blastoderm stages of drosophila embryogenesis the integrated activities of the cell cycle oscillator and actomyosin contractility generate a self-organized mechanism of nuclear positioning which is essential for synchronization of the cell cycle. At the core of this mechanism are cytoplasmic flows that are initiated by cortical contractions. These, in turn, are linked spatiotemporally to the oscillation of mitotic cyclin-dependent kinase 1 (CDK1) and protein phosphatase 1 (PP1). These flows are able to transport nuclei and are responsible for their accurate positioning across the embryo. The goal of this proposal is to build on these novel findings and to understand more deeply the mechanisms and developmental functions of cytoplasmic flows. We will take three approaches to address these fundamental questions. 1. We will build a biophysical model that captures the coupling of biochemical and mechanical signals and the effective physical properties of the cytoplasm. The coupling between the cytoskeleton and the cytosol will be modeled by a two- fluid model: an active contractile GEL and a viscous cytosol. 2. We will use genetic and optogenetics approaches to alter cortical contractility as well as transgenic approaches to change the geometry of the embryo and a novel setup to control temperature. These experiments will provide a novel paradigm for understanding the molecular mechanisms underlying the generation and the properties of cytoplasmic flows. 3. We will test whether cytoplasmic flows play a role in the formation of morphogen gradients. Specifically, we will use quantitative imaging and mathematical modeling to determine whether cytoplasmic flows affect the formation of the anterior- posterior gradient of bicoid morphogen in the syncytial drosophila embryo. Taken together these studies will provide a new paradigm for the integration of biochemical and mechanical signals that is likely to have general relevance for other developmental systems.
Transactions
| Action | Federal | Non-federal | Date |
|---|---|---|---|
| Amendment | -$6 | $0 | |
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| Amendment | $206,000 | $0 | |
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| Amendment | $288,761 | $0 | |
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| Amendment | $288,874 | $0 | |
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| Amendment | $301,256 | $0 | |
| Original award | $301,256 | $301,256 |
Show all 16
Subawards
| Subrecipient | Amount | Awarded |
|---|---|---|
| Ecole Normale Superieure | $243,000 |
Quick answers
Who received award R01GM136763?
R01GM136763 was awarded to Duke University by National Institute of General Medical Sciences (National Institutes of Health) on September 20, 2021.
How much is award R01GM136763 worth?
$2,759,785 has been obligated on R01GM136763: $2,458,529 in federal funding and $301,256 in non-federal funding.
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