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Identifying Plasmodium Liver-Stage Secreted Effector Proteins

Award Number: R21AI196824
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/02/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Identifying Plasmodium Liver-Stage Secreted Effector Proteins - PROJECT SUMMARY Malaria, caused by Plasmodium, remains a global health crisis, with over 250 million cases and 600,000 deaths annually. The liver stage of infection is a critical bottleneck, where Plasmodium invades hepatocytes, replicates, and progresses to the blood stage. While hepatocytes mount robust cell-intrinsic immune re- sponses to eliminate the parasite, some Plasmodium parasites evade these defenses, suggesting parasite- derived mechanisms to subvert host immunity. We hypothesize that Plasmodium exports effector proteins into the hepatocyte cytoplasm, nucleus, or the parasitophorous vacuole membrane (PVM) to neutralize host immune responses, enabling survival. This exploratory R21 proposal aims to define the secretome and in- teractome of the human malaria parasite Plasmodium falciparum (Pf) and the mouse malaria parasite P. berghei (Pb) in hepatocytes. Using proximity-dependent biotinylation (miniTurboID and split-TurboID) coupled with micro-proteomics and high-sensitivity mass spectrometry, we will identify Plasmodium proteins exported to the hepatocyte cytoplasm, nucleus, and PVM (Sub-Aim 1). We will validate the expression and localization of the candidate effectors using CRISPR/Cas9-mediated endogenous tagging and immunofluorescence mi- croscopy (Sub-Aim 2). This study will provide the first comprehensive map of liver-stage Plasmodium exported proteins in hepatocytes, uncovering candidates that are likely to mediate immune evasion and host-cell re- modeling. By identifying conserved effector proteins and defining when and where they act in the infected cell, this work will lay the foundation for future dissection of their host targets and mechanisms of action. Ultimately, these discoveries will enable the development of novel strategies to block parasite survival in the liver, potentially leading to new prophylactic or therapeutic interventions. Leveraging cutting-edge proteomic and molecular tools, our proposed research addresses a critical knowledge-gap in Plasmodium biology and has the potential to transform our understanding of liver-stage malaria.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $190,000 )
2026	2026	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	9/2/2026	NEW	$190,000
														Subtotal = $190,000

Grand Total All Awards = $190,000

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Identifying Plasmodium Liver-Stage Secreted Effector Proteins

Award Number: R21AI196824

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/02/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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