Molecular mechanisms of lysosome remodeling in response to cellular stress
Active Project Grant Awarded Last action
- Award ID
- R35GM159962
- Recipient
-
University Of Denver UEI WCUGNQQ8DZU1
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $815,124
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 22% complete
- Place of performance
- Denver, CO 80210, USA
Award details come from USAspending.gov.
Description
- Abstract
- The lysosome is a central catabolic station that breaks down and recycles materials from multiple pathways. Lysosome dysfunction will cause lysosomal storage diseases. In addition, lysosome dysregulation is also widely related to many other human diseases, such as neurodegenerative disorders, cardiovascular diseases, osteoporosis, and cancers. To function properly, the composition of lysosome membrane must be precisely regulated in response to environmental cues. Dysregulation in lysosome membrane composition leads to lysosome dysfunction and the development of lysosome-related diseases. Despite extensive research into many other aspects of lysosome biology, how lysosome adjusts its own composition in response to environmental cues remains poorly understood. Surprisingly, we found that many lysosome membrane proteins are degraded under starvation. This suggests that, rather than simply global biogenesis, the lysosome membrane undergoes dramatic remodeling, challenging the long-held view of how lysosomal composition is regulated. However, the cellular machinery and molecular mechanisms governing these processes are still largely unknown, positioning this proposed research at the forefront of the field. In this proposal, we will use budding yeast as a model system to address this emerging question through two major directions:1. Characterization of vacuole membrane protein (VMP) degradation pathways. 2. Vacuole remodeling through transcriptional regulation. Collectively, the results of our studies will advance the field by uncovering the new machinery and mechanisms involved in both the degradation and production aspects of lysosomal remodeling. Furthermore, this proposed research will be a critical first step in understanding the role of lysosomal remodeling in lysosomal function and lysosome-related diseases. IT will also lay the foundation for developing new therapeutic treatments that target lysosomal function by controlling its composition.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $407,562 | |
| Original award | $407,562 |
Quick answers
Who received award R35GM159962?
R35GM159962 was awarded to University Of Denver by National Institute of General Medical Sciences (National Institutes of Health) on September 1, 2025.
How much is award R35GM159962 worth?
$815,124 has been obligated on R35GM159962.
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