Understanding Malaria Parasite Pathogenesis by Cryo-Electron Microscopy
In this tutorial, you will learn:
- The mechanisms by which the plasmodium translocon of exported proteins (PTEX) enables the Plasmodium parasite to take over red blood cells
- How single-particle cryo-electron microscopy enables us to gain insight into the PTEX molecular structure
- The opportunity this presents for structure-based design of anti-malarial drugs.
- The unique strengths of cryo-EM as an experimental tool for approaching such analysis.
Dr. Chi-Min Ho
Malaria has devastated major civilizations since the dawn of humanity and remains a considerable burden to society; it is responsible for more than 200 million cases and nearly half a million deaths each year.
This infectious disease is caused by Plasmodium parasites, which invade and reproduce within human erythrocytes, inducing the clinical symptoms of malaria.
These parasites export hundreds of effector proteins that extensively remodel host erythrocytes, which have limited capacity for biosynthesis. Collectively known as the exportome, these proteins create the infrastructure necessary to import nutrients, export waste, and evade splenic clearance of infected erythrocytes.
The malaria parasite conceals itself inside a parasitophorous vacuole, which is derived from invagination of the host cell plasma membrane during invasion. Following secretion into the parasitophorous vacuole, proteins destined for export are unfolded and transported across the parasitophorous vacuole membrane (PVM) into the host cell in an ATP-dependent process.
To accomplish this the parasite has evolved a unique membrane protein complex, the Plasmodium translocon of exported proteins (PTEX).
This webinar will explain how single-particle cryo-electron microscopy enables us to gain insight into malaria research development through the detailed analysis of Plasmodium translocon of exported proteins (PTEX) core complex molecular structure and the opportunity it presents for structure-based design of anti-malarial drugs. We will also examine the unique strengths of cryo-EM as an experimental tool for approaching such analysis.
We will illustrate these aspects with some of the latest research from Dr. Chi-Min Ho in the laboratory of Dr. Hong Zhou at UCLA and assess the promises and challenges of cryo-EM in our fight against malaria.