Alan Cowman-Projects

Alan Cowman-Projects

Projects

Super Content: 
Microscopy image of malaria parasites in blood cell

Light microscopy at the Institute's Centre for Dynamic Imaging is giving researchers new insights into the behaviour of a deadly malaria-causing parasite.

How do malaria parasites invade red blood cells?

Plasmodium falciparum, the deadliest malaria-causing parasite, invades and multiplies within human red blood cells. The parasite first attaches to the red blood cell and its proteins bind to the receptors on the red blood cell surface.

We try to understand the interactions between the parasite and the host cell that lead to a successful invasion. Targeted protein depletion or antibody-mediated blocking of these interactions prevents the parasite from entering the red blood cell. Hence, it provides an attractive target for vaccine development.    

Team members: Wilson Wong, Tony Hodder, Julie Healer, Tony Triglia

Microscopy image of malaria parasite

Image: Malaria parasite (merozoite stage) during the invasion of a red blood cell. Dashed line outlines the parasite; green – protein on the parasite surface; red – parasite protein forming the junction between the parasite and the red blood cell; blue – parasite DNA. Credit: Dr Danushka Marapana

How does the malaria parasite survive inside the red blood cell?

Once inside the red blood cell, the parasite modifies it so that the cell can provide a safe environment for parasite growth and replication.

To achieve this, the parasite produces a huge number of proteins which are then delivered to various destinations within the red blood cell. Inhibition of this protein trafficking kills the parasite, so we try to understand the mechanisms of this process and how we can stop it.

Team members: Danushka Marapana, Michał Pasternak

Microscopy image of malaria parasite

Image: Super-resolution image of red blood cells (magenta). The middle cell has been infected with Plasmodium falciparum (DNA in blue, parasite protein in green) and contains multiple parasites ready to burst and invade new red blood cells. Credit: Dr Michał Pasternak

Development of novel antimalarial drugs

New treatments for malaria are urgently needed due to rapidly developing resistance to existing medications.

Our research team, in collaboration with Merck & Co., Inc., has already discovered novel drug-like molecules that prevent malaria parasites growing in human red blood cells. With the support of a $4.6 million grant from the Wellcome Trust we are working to improve these molecules and to test them against all parasite lifecycle stages. We aim to generate new drug-like compounds that will undergo preclinical and clinical testing as potential new antimalarial drugs.

Team members: Paola Favuzza, Julie Healer, Tony Hodder, Jenny Thompson, Bethany Davey

Structure diagram

Image: Structure of Plasmepsin V, an enzyme critical for parasite survival, with an inhibitor developed in the Institute. Credit: Dr Tony Hodder

Parasite transmission into and from the mosquito

Malaria-causing parasites are transmitted by mosquitoes that have fed on the blood of infected individuals. The mosquito is infected with parasite gametocytes, which undergo sexual reproduction inside the mosquito and give rise to sporozoites. Sporozoites reside in the salivary gland of the mosquito and are able to invade human hepatocytes when the mosquito feeds again.

Our lab tries to understand these processes and how to block them.

We have identified enzymes required for sporozoite formation and are now trying to understand their function. We are also interested in innovative ways to limit malaria transmission.

The Institute's mosquito insectary enables us to conduct research on malaria transmission.

Team members: Tup Reaksudsan, Julie Healer, Melissa Hobbs

Microscopy view of a mosquito

Image: Anopheles mosquito from the Institute insectary. Credit: Dr Qike Wang, Dr Verena Wimmer and Dr Julie Healer