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Last Updated: 17/12/2019
Nanoscale reconstruction of mechanical systems involved in disease pathogenesis
Objectives
The project has three overall goals:
- understanding the lifetime of molecular machines
- to reconstitute mechanical aspects of host-cell invasion by malaria parasites;
- 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
Principal Investigators / Focal Persons
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.
Project Outputs
External reference
Thematic Categories
Date
Sep 2018 — Jun 2023
Total Project Funding
$2.35M
Funding Details
National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), United States
Project Number: 1DP2AI144247
Project Site
Deep Dives