Translational control of conidial germination in aspergillus fumigatus
Active Project Grant Awarded Last action
- Award ID
- R21AI186304
- Recipient
-
The University Of Texas Health Science Center At San Antonio UEI C3KXNLTAAY98
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $794,375
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 82% complete
- Originally
- Place of performance
- San Antonio, TX 78229, USA
Award details come from USAspending.gov.
Description
- Abstract
- Aspergillus fumigatus is a major human fungal pathogen capable of causing a range of diseases, including invasive pulmonary aspergillosis and disseminated aspergillosis in a wide variety of immunocompromised individuals, including organ transplant recipients and cancer patients. Mortality rates are as high as 40-50% in these patients and direct healthcare costs associated with invasive aspergillosis, $4.6 billion in the U.S., are more than those of any other fungal infection. A. Fumigatus, normally found in the soil and environment, produces asexual conidia that are typically inhaled in the lungs. Under appropriate host environmental conditions conidia will germinate and eventually form hyphae that can not only penetrate lung tissue but also establish a disseminated bloodstream infection. Conidial germination is thus critical for a. Fumigatus virulence and pathogenesis. While a variety of post-translational and transcriptional regulators are known to play important roles in conidial germination, very little, if anything, is known about translational mechanisms. However, multiple lines of evidence suggest that translational regulation plays an important role, including the demonstration that conidial germination can be abrogated by inhibitors of translation, but not RNA or DNA synthesis, that dormant conidia harbor a significant number of stored transcripts, which are primed for rapid translation and activation, and that translation is one of the earliest detectable events in germinating conidia. In addition, a comparative proteomic and transcriptomic study indicated that many genes show significant differences in transcript VS. Protein expression changes during a. Fumigatus conidial germination and transcripts of several key regulators of this process possess unusually long 5' UTR regions, which have been associated with translational regulation of morphology and other virulence processes in the human fungal pathogen candida albicans. We have also recently used ribosome profiling to demonstrate that the c. Albicans yeast-hyphal morphological transition, which is similar to a. Fumigatus germination/polarized growth, is under widespread global translational regulation that does not simply parallel transcriptional regulation; many genes associated with virulence and virulence-related processes show altered translational efficiency. Based on this evidence, we hypothesize that translational mechanisms play an important role in controlling a. Fumigatus conidial germination, distinct from that of transcriptional mechanisms, which will reveal novel potential antifungal targets. In order to test this hypothesis, we will: 1) determine the global translational profile of a. Fumigatus during conidial germination, 2) identify and characterize translational mechanisms important for a. Fumigatus conidial germination. Ultimately, this study will provide a better understanding of global regulatory circuits and pathways controlling a. Fumigatus conidial germination at the translational level. This study will also identify and characterize several key translationally regulated factors important for a. Fumigatus conidial germination that could potentially serve as targets for novel and more effective antifungals.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $232,500 | |
| Amendment | $19,375 | |
| Amendment | $19,375 | |
| Amendment | $174,375 | |
| Amendment | $174,375 | |
| Original award | $174,375 |
Quick answers
Who received award R21AI186304?
R21AI186304 was awarded to The University Of Texas Health Science Center At San Antonio by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on June 21, 2024.
How much is award R21AI186304 worth?
$794,375 has been obligated on R21AI186304.
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