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Role of CSN5 in Entamoeba histolytica Viability and Protein Degradation

Presenters Name: 
Jay Padalia
Co Presenters Name: 
Primary Research Mentor: 
Swagata Ghosh
Secondary Research Mentor: 
Shannon Moonah
Time: 
9:30 - 10:15
Time of Presentation: 
2019 - 9:30am to 10:15am
Session: 
1
Location: 
Newcomb Hall Ballroom
Presentation Type: 
Poster
Presentations Academic Category: 
Science
Grant Program Recipient: 
Not a Recipient
Abstract: 

Entamoeba histolytica is a protozoan parasite that causes amebic colitis. Amebic colitis is a leading cause of diarrhea and is estimated to kill more than 55,000 people each year. However, there are no vaccines available and resistance to existing drugs presents an unavoidable threat. Therefore, identifying novel drug targets for improved therapeutic intervention is crucial. The role of protein degradation pathways in parasite biology and as a drug target is rapidly emerging. The ubiquitin-proteasome system (UPS) of protein degradation is conserved across all eukaryotes and is essential for life. We recently identified a parasite-encoded CSN5 protein that in mammalian cells modulate the activity of UPS. We have also found that the CSN5 homologues are highly conserved among protozoan parasites. Here we hypothesize that Entamoeba histolytica encoded CSN5 homologue (EhCSN5) is essential for its viability and regulates protein degradation by UPS. Our initial analysis by genetic knockdown and overexpression of a dominant negative mutant EhCSN5 shows that EhCSN5 expression is indeed required for normal parasite growth and viability. To test whether or not protein degradation is impacted upon inhibiting EhCSN5 we are currently generating amoeba expressing a fluorescent reporter construct to assay in vivo UPS activity. With this study we hope to uncover a new molecular target for treating not only Entamoeba infection but also infection caused by many pathogenic parasites harboring CSN5 homologue.