NEW DELHI, Oct 9: Researchers have identified a ‘guard mechanism’ for a protein which attacks microbes in infected cells, opening the possibility of new treatments for Toxoplasma, Chlamydia, Tuberculosis and even cancer.
A study, led by the University of Birmingham and published today (5th October) in Science has discovered the lock and key mechanism that controls the attack protein GBP1. GBP1 is activated during inflammation and has the potential to attack membranes within cells and destroy them.
The research has revealed how the attack protein is controlled through a process called phosphorylation, a process in which a phosphate group is added to a protein by enzymes called protein kinases. The kinase targeting GBP1 is called PIM1 and can also become activated during inflammation. Phosphorylated GBP1 in turn is bound to a scaffold protein, which keeps uninfected bystander cells safe from uncontrolled GBP1 membrane attack and cell death.
The newly discovered mechanism prevents GBP1 from attacking cell membranes indiscriminately, creating a guard mechanism that is sensitive to disruption by the actions of pathogens inside the cells. The new discovery was made by Daniel Fisch, a former PhD student in the Frickel lab working on the study.
Dr Daniel Fisch said: “This was a fantastic project to work on for the past six years and involved many research groups from all over the world. None of this would have been possible without help from our colleagues and friends at The Francis Crick Institute in London, EMBL in Grenoble (France), ETH Zurich (Switzerland) and Osaka University (Japan).”
Dr Eva Frickel, Senior Wellcome Trust Fellow at the University of Birmingham, who led the study explained: “This discovery is significant for several reasons. Firstly, guard mechanisms such as the one that controls GBP1 were known to exist in plant biology, but less so in mammals. Think of it as a lock and key system. GBP1 wants to go out and attack cellular membranes, but PIM1 is the key meaning GBP1 is locked safely away.”
“The second reason is that this discovery could have multiple therapeutic applications. Now we know how GBP1 is controlled, we can explore ways to switch this function on and off at will, using it to kill pathogens.”
Dr Frickel and her team conducted this initial research on Toxoplasma gondii, a single-celled parasite that is common in cats. Whilst Toxoplasma infections in Europe and Western countries are unlikely to cause serious illness, in South American countries it can cause reoccurring eye infections and blindness and is particularly dangerous for pregnant women. (Agencies)
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