Dissecting the Red Blood Cell Invasion Pathways of the Malaria Parasite Plasmodium knowlesi

Dissecting the Red Blood Cell Invasion Pathways of the Malaria Parasite Plasmodium knowlesi

Objectives

  • Unravel the process of red blood cell (RBC) invasion by malaria parasites, an important target for novel drugs and vaccines
  • Identify parasite factors which may be causing the rise in human infections
  • Identify novel vaccine candidates¬†
  • Develop a transgenic P. knowlesi model to test existing vaccine candidates for P. vivax

PI Institution(s)

Principal Investigator (PI)

Funding source(s)

Partner(s)

Abstract

The parasites produce a range of adhesive proteins enabling them to bind to specific proteins on the surface of red blood cells and establish the process of red blood cell invasion. Because of their crucial role in the invasion process these parasite proteins are important vaccine targets. They also determine how effectively parasites can replicate and so can affect disease severity as well as determining which hosts are susceptible to malaria.

In this project I will investigate the role of these proteins during the invasion process using a malaria parasite known as Plasmodium knowlesi. I will use highly efficient techniques to genetically modify the parasite and generate parasites in which I have deleted genes encoding the adhesive proteins. This will enable me to determine which are essential for invasion and which can be deleted without any effect on the invasion process. Using similar techniques I will also add fluorescent "tags" to each of the proteins coded by the target genes, so that I can determine where the adhesive proteins are in the cell and where they move during the invasion process. The "tags" will also allow me to identify parasite proteins that interact with the adhesive proteins as well as what they specifically bind to on the host red blood cell surface.

This will provide critical insight into the mechanism of invasion of all malaria parasites, as well as identifying precisely which parasite proteins and host proteins are required for P. knowlesi to invade human red blood cells. The latter is of particular importance as it may explain how a macaque malaria parasite is able to spread to infect humans and determine the potential for emergence of human-to-human transmission of the parasite.

http://gtr.rcuk.ac.uk/projects?ref=MR/M021157/1

Key facts

  • Dates
    Jul 2015 to Jun 2020
    Funding amount
    $1,805,966
    Funding information
    GBP 1,085,780 (MRC UK) + GBP 62,600 (Bloomsbury Colleges). Fellowship
    Country
    • United Kingdom

MESA tags

  • Methodology
    Basic science
    Theme(s)
    Measurement of transmission, Parasite genetic diversity, Tools for elimination