Events Calendar

Environmental and Occupational Health Sciences Journal Club

This is a past event.

EOH student Vania Polynice will present the article:

A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures

by Tintó-Font E, Michel-Todó L, Russell TJ, Casas-Vila N, Conway DJ, Bozdech Z, Llinás M, Cortés A

Abstract
Periodic fever is a characteristic clinical feature of human malaria, but how parasites survive febrile episodes is not known. Although the genomes of Plasmodium species encode a full set of chaperones, they lack the conserved eukaryotic transcription factor HSF1, which activates the expression of chaperones following heat shock. Here, we show that PfAP2-HS, a transcription factor in the ApiAP2 family, regulates the protective heat-shock response in Plasmodium falciparum. PfAP2-HS activates the transcription of hsp70-1 and hsp90 at elevated temperatures. The main binding site of PfAP2-HS in the entire genome coincides with a tandem G-box DNA motif in the hsp70-1 promoter. Engineered parasites lacking PfAP2-HS have reduced heat-shock survival and severe growth defects at 37 °C but not at 35 °C. Parasites lacking PfAP2-HS also have increased sensitivity to imbalances in protein homeostasis (proteostasis) produced by artemisinin, the frontline antimalarial drug, or the proteasome inhibitor epoxomicin. We propose that PfAP2-HS contributes to the maintenance of proteostasis under basal conditions and upregulates specific chaperone-encoding genes at febrile temperatures to protect the parasite against protein damage.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.  If a Zoom link is needed, please email nffitz@pitt.edu.

Thursday, April 7 at 11:00 a.m.

Public Health, A425
130 Desoto Street, Pittsburgh, 15261

Environmental and Occupational Health Sciences Journal Club

EOH student Vania Polynice will present the article:

A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures

by Tintó-Font E, Michel-Todó L, Russell TJ, Casas-Vila N, Conway DJ, Bozdech Z, Llinás M, Cortés A

Abstract
Periodic fever is a characteristic clinical feature of human malaria, but how parasites survive febrile episodes is not known. Although the genomes of Plasmodium species encode a full set of chaperones, they lack the conserved eukaryotic transcription factor HSF1, which activates the expression of chaperones following heat shock. Here, we show that PfAP2-HS, a transcription factor in the ApiAP2 family, regulates the protective heat-shock response in Plasmodium falciparum. PfAP2-HS activates the transcription of hsp70-1 and hsp90 at elevated temperatures. The main binding site of PfAP2-HS in the entire genome coincides with a tandem G-box DNA motif in the hsp70-1 promoter. Engineered parasites lacking PfAP2-HS have reduced heat-shock survival and severe growth defects at 37 °C but not at 35 °C. Parasites lacking PfAP2-HS also have increased sensitivity to imbalances in protein homeostasis (proteostasis) produced by artemisinin, the frontline antimalarial drug, or the proteasome inhibitor epoxomicin. We propose that PfAP2-HS contributes to the maintenance of proteostasis under basal conditions and upregulates specific chaperone-encoding genes at febrile temperatures to protect the parasite against protein damage.

PLEASE SUPPORT OUR STUDENT PRESENTERS

Organized by Dr. Nicholas Fitz of the Department of Environmental and Occupational Health, this weekly course is designed to expose EOH students to the newest and most exciting research in a diverse set of topics related to toxicology.  Guests are welcome.  If a Zoom link is needed, please email nffitz@pitt.edu.

Thursday, April 7 at 11:00 a.m.

Public Health, A425
130 Desoto Street, Pittsburgh, 15261

Event Type

Virtual

Topic

Research

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