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Linn Meret Unger

Linn Meret Unger

Boehringer Ingelheim International Scholar
Tierarztliche Hochschule Hannover
University of Veterinary Medicine Hannover
Class of 2019

Research Interests

The role of the golgi complex in Trypanosoma cruzi calcium homeostasis

Linn Meret Unger, Srinivasan Ramakrishnan, Roberto Docampo

Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA (Unger, Ramakrishnan, Docampo) College of Veterinary Medicine, University of Georgia, Athens, GA (Unger); University of Veterinary Medicine Hannover, Foundation, Germany (Unger)

The eukaryotic parasite Trypanosoma cruzi is the etiological agent of Chagas disease. Ca2+ signaling plays an essential role in its life cycle, bioenergetics, and in host cell invasion. In mammalian cells, the Golgi complex (GC) is known to play a heterogenous role in Ca2+ signaling and homeostasis, but little is known about its role in Trypanosoma cruzi. The purpose of this study was to characterize the function of the GC in T. cruzi Ca2+ homeostasis. Recently, a protein termed GDT1 was identified in yeast and mammalian GC as a Ca2+/H+ antiporter. An ortholog for GDT1 is found in T. cruzi and localizes to the parasite GC. To characterize this protein, we deleted TcGDT1 using a CRISPR/Cas9 strategy. We found that the GDT1 mutant grew much slower than control cell lines (wild type and transfected with a scrambled sgRNA). While wild type and scrambled parasites invaded about 24% of the host cells, GDT1 mutant invaded only 4.5% (n = 3, P < 0.03). Additionally, the replication rate of the GDT1 mutant amastigotes was reduced by 74% when compared to that of control cells. We are planning experiments using a mouse model to test the importance of this protein during in vivo infections. Additionally, both yeast and mammalian GDT1 contain an N-terminal signal peptide. But such signal peptide could not be detected in T. cruzi GDT1 protein. We are conducting experiments to test the presence of an unconventional signal peptide and to see if its sequence can be exploited to target a genetically encoded Ca2+ sensor to the T. cruzi GC. Together, these data will determine the role of GC in overall T. cruzi Ca2+ homeostasis. Additionally, these experiments may also lead to the discovery of new drug targets in T. cruzi.

Research Grant: NIH 1008222

Student Support: Boehringer Ingelheim Veterinary Scholars Program

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