Mechanisms directing translating complexes to plasma membranes for local translation
Ended Project Grant Awarded Last action
- Award ID
- F31GM153150
- Recipient
-
Colorado State University UEI LT9CXX8L19G1
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $245,696
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date
- Place of performance
- Colorado, USA
Award details come from USAspending.gov.
Description
- Abstract
- This proposal outlines a training program for independent scientist with a focus on mrna localization using genetics and molecular biology. The research outlined in this proposal will develop a platform to evaluate local translation, a process of whose disruption results in many neurological diseases and cancer. The phenomena directing local translation to axon termini and the endoplasmic reticulum (ER) have been described. Scientists have recently made the novel discovery that local translation also occurs at plasma membranes. For example, in caenorhabditis elegans, ezrin/radixin/moesin (ERM-1) mrna localizes to plasma membranes with its encoded protein, a plasma membrane-actin cytoskeleton linker that will coordinate cell shape changes. ERM- 1/ERM-1 undergoes translation-dependent localization and local translation directed by its N-terminal encoded ferm domain. However, neither the mechanisms directing their localization nor the reasons for their local translation are understood. The proposed research aims to use ERM-1 as a model to understand how mrna localization to the plasma membrane arises mechanistically, functionally links to protein production, and impacts gene expression. Based on preliminary evidence, the hypothesis is that cytoskeletal components interact with the translating complex to direct IT to the plasma membrane, similar to CO-translational transport of secretory proteins to the ER. This model will be explored from a genetics and molecular biology perspective with 3 specific aims. The first aim will test whether ERM-1/ERM-1 localization occurs through diffusion or directed transport mechanisms and explore which cytoskeletal components are required. The second aim will develop a live imaging tool to better resolve the kinetics of ERM-1 translation. The third aim will identify the effector proteins involved in this process. Since impaired mrna localization in neurons and other cell types causes disease but studying mrna localization in disease-specific models is challenging, this project will achieve our long-term goal of characterizing novel mrna transport pathways that have the potential to be generalizable in human health.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $564 | |
| Amendment | $41,282 | |
| Amendment | $41,282 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $40,002 | |
| Amendment | $40,002 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $40,002 | |
| Amendment | $40,002 | |
| Original award | $0 |
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Quick answers
Who received award F31GM153150?
F31GM153150 was awarded to Colorado State University by National Institute of General Medical Sciences (National Institutes of Health) on July 1, 2024.
How much is award F31GM153150 worth?
$245,696 has been obligated on F31GM153150.
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