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As part of our continuing effort to bring to you the latest developments in the field of science, we are proud to introduce a new section to our blog, Researcher of the Month (RotM), where we will speak about ground breaking research findings and to the researchers behind the work.
In our first RotM interview, we spoke to Dr. Justin Boddey, a researcher at the Infection and Immunity Division at the Walter and Eliza Hill Institute, Australia. Dr. Justin recently published his findings regarding Plasmepsin V in PLoS Biology, which has shed new light on our understanding of malarial parasite, Plasmodium, and how we can prevent its spread.
As part of our continuing effort to bring to you the latest developments in the field of science, we are proud to introduce a new section to our blog, Researcher of the Month (RotM), where we will speak about ground breaking research findings and to the researchers behind the work.
In our first RotM interview, we spoke to Dr. Justin Boddey, a researcher at the Infection and Immunity Division at the Walter and Eliza Hill Institute, Australia. Dr. Justin recently published his findings regarding Plasmepsin V in PLoS Biology, which has shed new light on our understanding of malarial parasite, Plasmodium, and how we can prevent its spread.
Here’s Dr. Justin telling us more about his findings.
CTS: For the benefit of our readers, please tell us about the fresh perspective that
Dr. Justin in his lab at WEHI
your recent findings have provided to tackling malaria.
JB: Malaria parasites are very clever; they invade red blood cells and change them by delivering more than 300 proteins into them. This is required for the malarial parasite to survive in our body but this is also what makes people feel sick. We have developed a drug-like compound that blocks a parasite enzyme, called Plasmepsin V (PMV), which controls protein delivery into red blood cells. This prevents malaria parasites from sufficiently changing the cells and they die.
CTS: How does the compound that you have developed block PMV?
JB: We developed PMV inhibitors, called WEHI-916, by copying the general shape of malaria proteins that PMV can recognise. The inhibitors bind to PMV and block its activity due to which malaria causing proteins cannot be transported correctly. If you think about PMV as a lock in a door, we developed a very small key that fits inside the lock and blocks any other key from gaining access. So the lock is now useless, and nothing can go through the door.
CTS: From your publication, we have found that WEHI-916, has a small window to be effective (20-30 hours after erthyrocyte invasion). How do you envisage the inhibitor to be successful in treating malaria?
JB: Actually, the inhibitor WEHI-916 blocks protein transport very early in the parasite’s lifecycle. However, it takes some time for the parasites to die from the blockage. Many antimalarial drugs have a specific window of activity, so this is not a big concern. Compounds based on WEHI-916 could be useful for prophylaxis, in addition to treatment of malaria.
CTS: What happens next? How does WEHI-916 become a drug against malaria?
JB:The development of WEHI-916 is the first step toward a new drug. However, WEHI-916 cannot become a marketable drug. It is a peptide. Its value lies in the demonstration that inhibition of Plasmepsin V kills the parasite. So future drugs that have the same activity would be possible drugs. We aim to work with people like the Medicines for Malaria Venture (MMV) to help in development of the drug and take it through clinical trials.
CTS:What are the hurdles when it comes to combating infectious diseases such as malaria?
JB: Drug resistance is a major hurdle since parasites evolve to overcome drugs that are effective against them. So, we have to constantly work on identifying new targets that may be suitable for inhibition by antimalarial drugs. For this, we study the molecular mechanisms underlying essential processes in parasites, such as how they survive inside the human cells they infect. That is why the demonstration that PMV is a valid antimalarial drug target is so exciting.
CTS: Of all diseases and disorders, why did you choose to study malaria?
JB: Malaria has plagued humans for over 100,000 years and is still an enormous global health problem today. So I believe it is a very important cause. I am also fascinated by the way malaria parasites manipulate their human host to ensure their own survival and am driven to understand this at the molecular level.
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CTS: For the benefit of our readers, please tell us about the fresh perspective that
your recent findings have provided to tackling malaria.
JB: Malaria parasites are very clever; they invade red blood cells and change them by delivering more than 300 proteins into them. This is required for the malarial parasite to survive in our body but this is also what makes people feel sick. We have developed a drug-like compound that blocks a parasite enzyme, called Plasmepsin V (PMV), which controls protein delivery into red blood cells. This prevents malaria parasites from sufficiently changing the cells and they die.
CTS: How does the compound that you have developed block PMV?
JB: We developed PMV inhibitors, called WEHI-916, by copying the general shape of malaria proteins that PMV can recognise. The inhibitors bind to PMV and block its activity due to which malaria causing proteins cannot be transported correctly. If you think about PMV as a lock in a door, we developed a very small key that fits inside the lock and blocks any other key from gaining access. So the lock is now useless, and nothing can go through the door.
CTS: From your publication, we have found that WEHI-916, has a small window to be effective (20-30 hours after erthyrocyte invasion). How do you envisage the inhibitor to be successful in treating malaria?
JB: Actually, the inhibitor WEHI-916 blocks protein transport very early in the parasite’s lifecycle. However, it takes some time for the parasites to die from the blockage. Many antimalarial drugs have a specific window of activity, so this is not a big concern. Compounds based on WEHI-916 could be useful for prophylaxis, in addition to treatment of malaria.
CTS: What happens next? How does WEHI-916 become a drug against malaria?
JB:The development of WEHI-916 is the first step toward a new drug. However, WEHI-916 cannot become a marketable drug. It is a peptide. Its value lies in the demonstration that inhibition of Plasmepsin V kills the parasite. So future drugs that have the same activity would be possible drugs. We aim to work with people like the Medicines for Malaria Venture (MMV) to help in development of the drug and take it through clinical trials.
CTS:What are the hurdles when it comes to combating infectious diseases such as malaria?
JB: Drug resistance is a major hurdle since parasites evolve to overcome drugs that are effective against them. So, we have to constantly work on identifying new targets that may be suitable for inhibition by antimalarial drugs. For this, we study the molecular mechanisms underlying essential processes in parasites, such as how they survive inside the human cells they infect. That is why the demonstration that PMV is a valid antimalarial drug target is so exciting.
CTS: Of all diseases and disorders, why did you choose to study malaria? JB: Malaria has plagued humans for over 100,000 years and is still an enormous global health problem today. So I believe it is a very important cause. I am also fascinated by the way malaria parasites manipulate their human host to ensure their own survival and am driven to understand this at the molecular level. |
2 comments
Great read. It will be exciting to see how medicinal chemistry will be used to make a range of peptidomimetics against PMV.
Hey Christopher,
Glad you liked our post! It will indeed be interesting to see how well we can exploit this finding about PMV to prevent malaria.
But that's the best part of science! Its never a one man's job. It needs collaboration, information sharing and welcomes different approaches to the same problem!
So,the possibilities are endless!