Investigation of ApiAP2 Transcription Factor PF3D7_0420300 in Plasmodium falciparum
Open Access
- Author:
- Kelly, Erin
- Area of Honors:
- Biochemistry and Molecular Biology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Manuel Llinas, Thesis Supervisor
Song Tan, Thesis Honors Advisor - Keywords:
- malaria
plasmodium falciparum
transcription factor - Abstract:
- Malaria is an incredibly devastating disease, infecting more than 200 million people and causing over 400,000 deaths annually. The disease malaria is caused by a unicellular eukaryotic parasite from the genus Plasmodium, with P. falciparum being the most virulent.1As of now, there is no vaccine against this parasite, and many antimalarials that once were successful have begun to fail due to drug resistance. It is of the utmost importance to further investigate the Plasmodium falciparum parasite in order to discern potential new drug or vaccine targets. This is not an easy feat, for P. falciparum is an extremely complex organism. This parasite is transferred from a mosquito to humans, initially inhabiting the human hepatocytes then the human erythrocytes for much of the infection. Recently, the whole genome of P. falciparum had been sequenced, leading to further discoveries of genetic components including transcriptional regulators. Uniquely, much of the parasite’s life is regulated by a major family of sequence-specific transcription factors known as the ApiAP2 proteins. There are only 27 known ApiAP2 proteins, and moreover, these proteins only contain plant homology, making them a good potential future vaccine or drug target. Additionally, the ApiAP2 expression is highly regulated in a cascading manner throughout the intraerythrocytic life cycle. This fact points to the importance of the regulators, however, only a handful of these proteins have been fully characterized. This project aims to characterize the role of the ApiAP2 protein, PF3D7_0420300. Very little is known about this protein; however, PF3D7_0420300 has been predicted to be essential, thus investigation into this protein could yield information critical in identifying the next major drug target. To characterize this protein, a tagged line as well as a conditional knock down system must be generated. I used several methods to accomplish this: FKBP destabilization domain, glmS ribozyme cleavage, and CRISPR/Cas9 gene editing. The establishment of these parasite lines is a great advancement in and of itself, and this progress may allow for a future researcher to continue the critical characterization of PF3D7_0420300.