Last Updated: 17/12/2019

Nanoscale reconstruction of mechanical systems involved in disease pathogenesis

Objectives

The project has three overall goals: 

  1. understanding the lifetime of molecular machines
  2. to reconstitute mechanical aspects of host-cell invasion by malaria parasites; 
  3. to understand how force exerted on both the parasite and the host-cell are orchestrated, while persistently bearing the load associated to the malaria parasite moving into the host cell.

These objectives will be achieved through:

  • to determine the turnover number or the enzymatic lifetime of myosin motors through gliding assay
  • to design and construct 3D DNA origami scaffolds to precisely control the number of myosin VI motors
  • to investigate inter-molecular mechanical forces in malaria parasite invasion through Protein Unfolding by Mechanical Actuation (PUMA) platform, which a mechanically-active DNA platform for parallel manipulation of single proteins. 
  • to study the collective movement of myosin VI ensemble on two-dimensional actin network
Principal Institution

Arizona State University

Principal Investigators / Focal Persons

Rizal Fajar Hariadi

Rationale and Abstract

Malaria parasite invasion is a mechanical event that is powered by an active machinery, known as the “glideosome”. The current working model of glideosomes postulates that mechanical forces are generated by highly dynamic actin-myosin interactions inside the parasites. These forces are applied to proteins at the interface between the parasite and the host-cell. 

Thematic Categories

Enabling Technologies & Assays

Date

Sep 2018 — Jun 2023

Total Project Funding

$2.3M

Project Site

United States

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