Molecular mechanisms in pediatric cerebral malaria pathogenesis and Immunity
| dc.contributor.author | Seydel, Karl | |
| dc.date.accessioned | 2021-12-21T10:47:23Z | |
| dc.date.available | 2021-12-21T10:47:23Z | |
| dc.date.issued | 2021-07-21 | |
| dc.description.abstract | Type of Research Study: Prospective case control study Problem: Malaria, caused by the parasite P. falciparum, remains a significant public health problem in Malawi. Objectives: We plan to 1) determine which subset of parasites are responsible for binding to the microvessels of the brain and gut, and 2) investigate the role of lactate in altering the binding characteristics of parasitized erythrocytes to microvessels. Methodology: We have devised a novel 3D microvessel model that accurately mimics the flow velocity and wall shear stress present in the microvessels of the brain. We are able to create an in vitro model of the human brain microcirculation by forming very small 3D blood microvessels from primary human brain endothelial cells, thus accurately mimicking both the cellular and fluidic environment that a parasitized erythrocyte would encounter in the brain. We will use this 3D human brain microvessel model, as well as characterized parasites from malaria patients to investigate the receptors and milieu contributing to life-threatening cerebral malaria infections. Expected findings and dissemination: We anticipate finding a subset of parasites, those expressing a certain subset of PfEMP1 molecules on their surface, that are most adept at binding to brain endothelial cells. We anticipate that the innovative 3D microvessel model will elucidate parasite binding differences under certain flow-based, shear stresses that have not previously been appreciated, given previous models were unable to mimic physiologic flow and the curvature of a blood vessel wall. We also anticipate being able to use this unique model, in combination with known antibodies and shRNA techniques to determine the role of various proteins on the endothelial cell surface in mediating this binding. Moreover, we will determine if different subsets of parasites will adhere to brain and gut microvessels, which are the predominant organs of parasite accumulation in deadly malaria infections. Finally, we will be able to use this model to evaluate the role of external molecules, such as lactate, on infected erythrocyte binding in a physiologically relevant model system. Results will be disseminated in peer-reviewed journals, international conferences, the University of Malawi College of Medicine Research Dissemination Conference, and will be provided to COMREC and community leaders. | en_US |
| dc.description.sponsorship | Kamuzu University of Health Sciences, Blantyre Malaria Project Michigan State University, Department of Osteopathic Medical Specialties Seattle Children’s Research Institute, Center for Global Infectious Disease Research University of Washington, Department of Bioengineering | en_US |
| dc.identifier.uri | http://rscarchive.kuhes.ac.mw/handle/20.500.12988/668 | |
| dc.language.iso | en | en_US |
| dc.publisher | Kamuzu University of Health Sciences | en_US |
| dc.relation.ispartofseries | Protocol;P.06/21/3343 | |
| dc.title | Molecular mechanisms in pediatric cerebral malaria pathogenesis and Immunity | en_US |
| dc.type | Plan or blueprint | en_US |