Characterizing the unusual Protein Trafficking Pathways of Plasmodium falciparum
Angelica Barrero-Tobon
Majors: Molecular Biology and Microbiology
Mentor: Dr. Debopam Chakrabarti, Burnett College of Biomedical Sciences
Angelica M. Barrero-Tobon was born in Bogota, Colombia. Her research interests include infectious diseases and public health. In addition to research through the McNair program, she is involved with the Research and Mentoring Program at UCF. She is interested in attending either UCSD or UC Berkeley to obtain a PhD in Molecular Biology, Biomedical Sciences or Molecular Pathology. Her graduate research interests include epidemiology and the public health aspect of infectious diseases.
The following abstract is from research conducted under the guidance of Dr. Debopam Chakrabarti (Burnett College of Biomedical Sciences), as part of the UCF Research and Mentoring Program (RAMP).
Malaria caused by Plasmodium falciparum afflicts an estimated 300-500 million people worldwide, and kills a child every 30 seconds in Africa. The parasite resides within human red blood cells and exports over 400 proteins into the host cell compartment that contribute to the pathophysiology of the disease. Transport of parasite proteins across infected red blood cells is unusual and is believed to occur through several ill-defined pathways. Malaria parasites also target nuclear-encoded proteins to several destinations within its cytoplasm, some of which are unique to this organism. The mechanisms by which parasite proteins are selectively targeted to locations within and beyond the parasite plasma membrane are not well understood, but are thought to involve transport vesicles that bud from donor membranes and migrate to target compartments where fusion occurs. Fusion of transport vesicles is mediated by members of a family of proteins called SNAREs. Recently, we reported the identification of eighteen SNARE proteins in the malaria parasite some of which exhibit novel structural features unique to Plasmodium falciparum. One such protein, PfSec22p, contains up to two transmembrane domains and was shown to localize to destinations within infected host cells different from that of its counterparts in yeast and humans. The present study aims at determining the role of the two transmembrane domains in PfSec22p functions and targeting. We have generated parasite cell lines that express either wild type or mutant forms of PfSec22p fused with green fluorescence proteins (GFP). Localization dynamics of the mutant proteins in transfected parasites will be examined by live imaging using a confocal microscopy, while subcellular locations will be determined by immunofluorescence assays using antibodies to various organellar markers. These studies contribute to current efforts aimed at understanding malaria protein trafficking pathways, and could facilitate drug development against the human plague.
The following abstract is from research conducted at the University of California at San Diego, under the guidance of Dr. Aleem Siddiqui (Division of Infectious Diseases), as part of the Summer Training Academy for Research in the Science (STARS) program.
Liver Cell Autophagy Alterations Caused by Infection with Hepatitis C Virus
Hepatitis C virus (HCV), an RNA virus that targets liver cells, is the main cause of chronic hepatitis, cirrhosis and hepatoma carcinoma. Its host cell invasion mechanism and survival is not completely understood, and only recently an efficient HCV infection system became available. The expression of viral proteins disrupts the regular processes in the cell, but maintaining minimal conditions that ensure host cell survival. Autophagy is a natural occurring process in the cell, initiated as response to viral infection, starvation, or the presence of defective organelles. As a result of autolysosome formation and cytoplasmic compartment degradation, the cell obtains raw material such as free amino acids, nucleotides or fatty acids that are then recycled. The purpose of this study is to investigate the alterations on the autophagic process due to HCV RNA genome expression. Through Western blotting analysis and immunoflourescent assays, we will determine if upon infection, autophagy is upregulated or downregulated. More specifically, we will examine Beclin 1 and LC3 proteins as autophagy markers in subgenomic replicon bearing cells and HCV infected cells. The results of this investigation are likely to reveal clues for future research of efficient treatments and possible design of antiviral strategies.