Evaluating the role of p38 in parasite-perturbed endothelial cells
Overview of opportunity:
Plasmodium falciparum malaria parasites cause excessive activation of human brain endothelial cells, leading to dysfunction of the blood-brain barrier during cerebral malaria. The activation of several host proteins is implicated in parasite-induced cellular dysfunction. Our lab is interested in investigating how P. falciparum parasites perturb host cell signaling pathways to cause cellular dysfunction, as a deeper understanding of these processes can lead to life-saving therapeutics.
p38 mitogen-activated protein kinase (MAPK) is a stress-induced host protein that we have shown is activated in human brain endothelial cells in response to P. falciparum parasites. The goal of this project is to determine the function of activated p38 MAPK in human brain endothelial cells. Our preliminary data suggests that p38 MAPK is involved in proinflammatory signaling in endothelial cells.
The students will confirm the finding that p38 MAPK is upstream of proinflammatory gene expression at the transcriptional and protein level using RT-qPCR and ELISA. They will also determine how p38 activation leads to proinflammatory gene expression. They will use a chemical inhibitor of p38 to evaluate the specificity of the observed phenotypes. To perform these studies, the students will learn how to culture human brain endothelial cells and P. falciparum parasites. Other techniques that may be used are barrier function assays and microscopy-based immunofluorescence assays.
While the goals of this project have been defined above, students will have the opportunity to shape the direction of the project.
Essay prompt:
Why do you want to work on this project and in the Dankwa lab? What qualities do you possess that make you well-suited to working in a lab? Word limit: 500.
Working on this project will give students the opportunity to learn a wide range of molecular and cell biology techniques and approaches that are translatable to diverse research settings, including labs in academia and industry. Furthermore, by performing experiments and participating in weekly lab meetings and journal club discussions, students will hone their communication, analytical and critical thinking skills – life skills that are important, regardless of students’ future careers. While working in the Dankwa lab, students will have the opportunity to interact with members of the lab at different stages of their research training, including a research fellow who is a recent college graduate, and graduate students. Lastly, experimental data obtained from this project may be included in a publication that is planned for submission by the end of the year.