Malaria is a potentially fatal mosquito-borne disease caused by the Plasmodium parasite that infects hundreds of millions of people each year. According to WHO, Plasmodium falciparum is the most deadly species and over the past few decades, it has gained resistance to drugs commonly used to treat Malaria, such as chloroquine, sulfadoxine, etc. especially in Southeast Asia. Artemisinin Combination Therapy (ACT) is our last line of defense and there is growing evidence of pathogen resistance to Artemisinin worldwide, potentially making malaria untreatable in the years to come.
Our project aims to tackle this problem by designing a novel class of orally administering peptide drugs to treat malaria and overcome the antimicrobial resistance of the pathogen. We aim to create a library of inhibitory peptide molecules, which target multiple, crucial host-pathogen interactions in the blood stage of Plasmodium falciparum malaria, effectively preventing the parasites from infecting human red blood cells (RBCs).
The drug consists of two parts: an inhibitory peptide and a cyclotide backbone.
Using in-silico modeling, we create inhibitory sequences for specific human - parasite protein interactions, which are then grafted into the cyclotide Kalata B1. The drug works by outcompeting the host epitope, thus preventing infection.
Successfully eradicating malaria requires us to address the complex interaction of the various factors that cause the prevalence of the disease. Keeping this in mind, we wanted to create a project that would address all the different aspects of the disease. Through our research and on talking to various experts, we realized that a lack of infrastructure in remote areas was a significant hindrance to eliminating the disease.
The current gold standard for the diagnosis of malaria requires access to a lab with the technical expertise to identify malarial parasites and sophisticated microscopes. However, in isolated and remote areas, this poses a huge challenge in accurately diagnosing malaria, which affects the treatment patients can avail. In order to bridge this gap, we also aim to create a portable diagnostics kit that will effectively enable healthcare workers to increase their testing capabilities. All they have to do is capture an image of a blood smear using a smartphone and test for the presence of malaria parasites using a Web API and voila, you have a diagnosis of whether a patient has malaria!
Our project is quite a lab intensive and took a hit with the Covid-19 imposed lockdown, while the team disbanded to their homes as our college shut down. Working remotely was a new and initially difficult experience, but an incredibly rewarding one. We learned to navigate challenges creatively and efficiently, often at the expense of our sleep cycles.
Ultimately it was the cooperation and commitment of the team, along with our incredibly helpful Ph.D. mentors that allowed us to sail through. The journey has had its fair share of ups and downs, just like every other journey, but the prospect of making a significant impact on the world and our motivation for it is ultimately what kept us going.
At the end of the day, we hope that our project is a useful contribution in the ongoing efforts to fight Malaria worldwide and to make treatment accessible to all.
- iGEM IISER Pune
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