Molecular mechanisms driving the adaptation of Plasmodium knowlesi to humans

Molecular mechanisms driving the adaptation of Plasmodium knowlesi to humans

Objectives

  • To compare the genome of Plasmodium knowlesi isolates from patients with severe and uncomplicated malaria and a reference strain.
  • To in vitro culture adapt P. knowlesi isolates obtained from patients with severe and uncomplicated malaria.
  • To compare the intrerythrocitic transcriptome of Plasmodium knowlesi isolates from patients with severe and uncomplicated malaria and a reference strain.
  • To identify and correlate changes in the parasite transcriptome and genome with host adaptation as well as virulence.

PI Institution(s)

Principal Investigator (PI)

Funding source(s)

Abstract

A new challenge has arisen in South East Asia due to P. knowlesi, a simian parasite normally found to infect the macaque monkeys causing a significant number of human malaria infections. Today, P. knowlesi infections are the major cause of human malaria in certain regions. It is not known whether P. knowlesi is solely transmitted from the monkey to the human or whether human to human transmission is possible. The discovery of P. knowlesi as a significant threat to humans makes it of critical importance to understand the changes that drive adaptation to humans as well as the molecular factors leading to severe disease in human patients.

The hypotheses here are:

  1. Genetic or transcriptional changes will provide insights into the molecular changes that underpin adaptation of P. knowlesi to humans
  2. Parasites that cause severe disease vs uncomplicated disease will have either genomic or transcriptomic differences.

Taken together this study will provide us with a comprehensive understanding of parasite factors that contribute to virulence.

Key facts

  • Funding information
    Singapore Ministry of Education Academic Research Fund Tier 1
    Country
    • Singapore

MESA tags

  • Theme(s)
    Measurement of transmission, Parasite genetic diversity