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Grants - AWARD SUMMARY


GEORGETOWN UNIVERSITY (THE)


Candida albicans is an opportunistic fungal pathogen and the major cause of human fungal infections. It resides commensally on the mucosal tissues of the human body in immunocompetent individuals. However, it is also responsible for causing superficial mucosal infections and life-threatening systemic infections, particularly in those who are immunocompromised. The morphology of this fungus changes from a yeast form to pseudohyphae and true hyphae. The transition from the yeast form to the filamentous forms is linked to virulence. C. albicans responds to environmental signals to alter its cell morphology, switching from the yeast form to the filamentous forms (termed the dimorphic transition). A number of factors have been identified that serve as triggers for this transition including pH, temperature, starvation for nitrogen, amino acid levels, and the presence of serum. Understanding how the cell senses and responds to its environment is important in understanding its pathogenesis. We are investigating a transcription factor that, when mutated, blocks the ability of the cell to undergo the dimorphic transition. This mutant also exhibits decreased virulence. We plan to investigate changes in gene expression through northern analysis and micro-array studies. We will identify the target genes through chromatin immunoprecipitation. We will also determine the epistatic relationship between this gene and other genes known to be involved in hyphal formation.

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AWARD OVERVIEW

AWARD OVERVIEW
Award Number 3R03AI075226-02S1 Funding Agency Department of Health and Human Services
Total Award Amount $7,675 Project Location - City Washington
Award Date 07/14/2009 Project Location - State DC
Project Status Completed Project Location - Zip 20057-1789
Jobs Reported 0.50 Congressional District 98
Project Location - Country US

Recipient Information (Grants)

Recipient Information (Grants)
Recipient Name GEORGETOWN UNIVERSITY (THE)
Recipient DUNS Number 049515844
Recipient Address 37TH & O STS NW
Recipient City WASHINGTON
Recipient State District of Columbia
Recipient Zip 20057-0001
Recipient Congressional District 98
Recipient Country USA
Required to Report Top 5
Highly Compensated Officials
No

Projects and Jobs Information

Projects and Jobs Information
Project Title MICRORNAS IN GIARDIA PATHOGENESIS
Project Status Completed
Final Project Report Submitted Yes
Project Activities Description Biological & Life Sciences
Quarterly Activities/Project Description The ARRA Supplement supported an undergraduate student, Alexandra Porcu, during the summer months of 2009; Alex performed the following: *(1) cAMP measurements. *WT and /fil2-/null mutant strains were grown overnight and transferred into 10% serum which induces hyphal formation in the WT but not in the mutant. Cells were harvested at various times after transfer, cell extracts were prepared, and cAMP measurements were made by comparison with standards. The levels of cAMP rose in the WT with a peak at 45-min; the levels of cAMP also rose in the /fil2-/null mutant but only to about 50-60% of the WT. This result suggests a defect in cAMP production, although this finding needs to be confirmed. *(2) Monitoring of hyphal development during treatment with db-cAMP and caffeine. *We predicted that both db-cAMP (a non-hydrolysable form of cAMP) and caffeine (which inhibits cAMP phosphodiesterase) would promote hyphal formation in the WT but not in the /fil2-/null mutant. We found that caffeine inhibited growth but did not restore filamentation in the /fil2/ mutant. The addition of db-cAMP inhibited filamentation in both the WT and /fil2 /mutant; this latter finding was unexpected. *(3) DNA microarray analysis.* A post-doctoral associate had previously performed a DNA microarray analysis, comparing the transcriptome of WT and /fil2 /mutant strains at 5-hr after transfer to 10% serum. Alex updated the description of the genes found up- and down-regulated by looking at the annotation of each ORF from the /Candida /Genome Database. She grouped the differentially expressed genes using GO terms. Several genes that are expressed in hyphae, such as /ECE1 /and /HWP1/, were severely down-regulated in the /fil2/ mutant. Interestingly, genes associated with mitochondrial function and stress responses were up-regulated. Additionally, she found that the genes encoding the thiamine biosynthesis pathway were also strongly down-regulated in the /fil2 /mutant.
Jobs Created 0.50
Description of Jobs Created Research Assistant I SR Systems Engineer


Purchaser Information (Grants)

Purchaser Information
Contracting Office ID Not Reported
Contracting Office Name Not Available
Contracting Office Region Not Available
TAS Major Program 75-0900

Award Information

Award Information
Award Date 07/14/2009
Award Number 3R03AI075226-02S1
Order Number
Award Type Grants
Funding Agency ID 75
Funding Agency Name Department of Health and Human Services
Funding Office Name Not Available
Awarding Agency ID 75
Awarding Agency Name Department of Health and Human Services
Amount of Award $7,675
Funds Invoiced/Received $7,675
Expenditure Amount $7,675
Infrastructure Expenditure Amount $0
Infrastructure Purpose and Rationale Not Reported
Infrastructure Point of Contact Name Not Reported
Infrastructure Point of Contact Email Not Reported
Infrastructure Point of Contact Phone Not Reported
Infrastructure Point of Contact Address Not Reported
Infrastructure Point of Contact City Not Reported
Infrastructure Point of Contact State Not Reported
Infrastructure Point of Contact Zip Not Reported

Product or Service Information (Grants)

Product or Service Information
Primary Activity Code U50 - NTEE
Activity Description Biological & Life Sciences

Sub-Awards Information

Sub-Awards Information
Sub-awards to Organizations 0
Sub-award Amounts to Organizations $0
Sub-Awards to Individuals 0
Sub-Award Amounts to Individuals $0
Number of Sub-awards less than $25,000/award 0
Amount of Sub-awards less than $25,000/award $0
Number of payments to vendors greater than $25,000 0
Total Amount of payments to vendors greater than $25,000/award $0
Number of payments to vendors less than $25,000/award 5
Total Amount of payments to vendors less than $25,000/award $1,000







Project Location Detail

Location Information
Latitude, Longitude 38º 54' 27", -77º 4' 17"
Congressional District 98
Address 1 37th & O Street NW
Address 2
City Washington
County District of Columbia
State DC
Zip 20057-1789
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