Biomod/2011/MIT/Origami/Malaria

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[[Biomod/2011/MIT/Origami/Process | <font face="courier new" style="color:#ffffff"> '''Process''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Biomod/2011/MIT/Origami/Potential | <font face="courier new" style="color:#ffffff"> '''Potential''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Biomod/2011/MIT/Origami/ScrappedIdeas | <font face="courier new" style="color:#000000"> '''Scrapped Ideas''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
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[[Biomod/2011/MIT/Origami/ScrappedIdeas | <font face="courier new" style="color:#000000"> '''Tentative Ideas''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Biomod/2011/MIT/Origami/TeamMembers | <font face="courier new" style="color:#ffffff"> '''Team Members''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Biomod/2011/MIT/Origami/TeamMembers | <font face="courier new" style="color:#ffffff"> '''Team Members''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Biomod/2011/MIT/Origami/Literature | <font face="courier new" style="color:#ffffff"> '''Literature''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;
[[Biomod/2011/MIT/Origami/Literature | <font face="courier new" style="color:#ffffff"> '''Literature''' </font>]] &nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;

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Home        Motivation        Process        Potential        Tentative Ideas        Team Members        Literature        Software      


Contents

Introduction

Malaria is a mosquito-borne infectious disease caused by protozoans, eukaryotic protists. Around 200 million people are infected every year, especially in tropical and subtropical regions and mostly in Africa. The majority of deaths are seen in young children in sub-Saharan Africa.

There are four types of human malaria:

  • Plasmodium falciparum (severe)
  • Plasmodium vivax
  • Plasmodium ovale
  • Plasmodium malarie

The parasite develops via two phases: exoerythrocytic phase (infection of hepatic system or liver) and erythrocytic phase (infection of red blood cells).

The plasmodium species replicate in host erythrocytes. The parasite enters and releases hundreds of effector proteins into its cytoplasm . Proteins destined for export contain a conserved pentameric motif known as PEXEL, which is cleaved by aspartyl protease, plasmepsin V, in the endoplasmic reticulum and transported to host cells. This cleavage sends a signal at the amino terminus of the cargo proteins for export to the host cell through a channel in the parasite's outer membrane.

The spleen serves as a filter of red blood cells. When infected red blood cells pass through the spleen, they are destroyed. The malaria parasite, to prevent its destruction, displays adhesive proteins (PfEMP1) on the surface of red blood cells, causing them to stick to the walls of blood vessels. These proteins are very hard to target because they are very diverse.

Treatments

The choice of treatment depends on which drug the parasites in the area are resistant to.

The following drugs can be used as prevention and treatment of malaria:

  • Mefloquine (Lariam)
  • Doxycycline
  • Combination of atovaquone and proguanil hypochloride (Malarone)

The best available treatment, particularly for P. falciparum malaria, is artemisinin-based combination therapy (ACT).

Patients usually discontinue the use of medication once symptoms disappear, but they still have dormant parasites in their blood which can infect a mosquito and then be passed on to another person. This is prevented by the ACT therapy, which follows up the first treatment with another drug.

Idea

The very general idea was to use DNA nanostructures to analyze how Plasmodium uses a transmembrane pump to expel drugs from the cell that would otherwise kill the parasite. The idea behind that was to hopefully create a useful tool for gathering data that would be useful in drug development

Malaria Literature

Malaria Mechanism Revealed A protein on the surface of the parasite, EBA-175, binds to glycophorin A, a receptor protein on the surface of red blood cells. If the parasite doesn't bind soon after it is released from the liver cells, it dies. EBA-175 has two RII molecules that come together resembling a handshake. The overall shape resembles a donut with two holes. This handshake interaction attaches the parasite protein onto the glycophorin A receptor. Link

Structural Basis for the EBA-175 Erythrocyte Invasion Pathway Link

This paper from 2006 details the invasion of red blood cells by malaria. Discussed are the initial interactions which are nonspecific but large in volume and then the proper orientation and entry into the cell, which can occur as fast as 60 seconds Link

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