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Credit: Ute Frevert
and Margaret Shear
Researchers say they’ve developed a new computational method to predict the function of disease-causing genes and proteins, and this has enabled an important discovery.
The team used the method to study EXP1, a protein known to be essential to the malaria parasite Plasmodium falciparum, although its exact mechanism has been unclear.
The research revealed that EXP1 enables the parasite to detoxify the main metabolic byproducts it creates in red blood cells.
The researchers also found that EXP1 has a direct role in drug action and susceptibility to artesunate, an important member of the artemisinin drug family.
“Through this multiyear collaborative effort, we now have an improved understanding of the protective molecular mechanisms of the malaria parasite and its drug susceptibility to artesunate,” said study author Olivier Lichtarge, MD, PhD, of the Baylor College of Medicine in Houston, Texas.
“As we are witnessing a rise of resistance to artemisinins, these results may help [us in] finding new pathways to successor drugs.”
Dr Lichtarge and his colleagues described this research in Cell.
The team devised a computational method that allows biological information to flow from gene to gene across the supergenomic network.
“The network connects millions of genes from hundreds of species based on their interactions within the organism or based on their ancestral relations between different species,” said study author Andreas Martin Lisewski, PhD, also of the Baylor College of Medicine.
“Normally, computing the flow of functional information would be costly and slow, but we developed a compression method that reduces this gigantic network into one that is much smaller and now computationally tractable. The surprise is that these biological networks are compressible, much like digital data in today’s computers.”
To test their method, the researchers looked at functional predictions of P falciparum. It’s been more than 10 years since this parasite’s genome was fully sequenced, but little is known about the function for most of its genes.
“To better understand this disease, we need to identify more functions of the parasite’s genes,” Dr Lisewski said. “This understanding may eventually help us to stem the rise of drug-resistant malaria, such as the emerging resistance to artemisinins.”
With that in mind, the researchers used their computational method to study EXP1. And they discovered the protein is a membrane glutathione S-transferase that degrades cytotoxic hematin but is inhibited by artesunate. 
Credit: Ute Frevert
and Margaret Shear
Researchers say they’ve developed a new computational method to predict the function of disease-causing genes and proteins, and this has enabled an important discovery.
The team used the method to study EXP1, a protein known to be essential to the malaria parasite Plasmodium falciparum, although its exact mechanism has been unclear.
The research revealed that EXP1 enables the parasite to detoxify the main metabolic byproducts it creates in red blood cells.
The researchers also found that EXP1 has a direct role in drug action and susceptibility to artesunate, an important member of the artemisinin drug family.
“Through this multiyear collaborative effort, we now have an improved understanding of the protective molecular mechanisms of the malaria parasite and its drug susceptibility to artesunate,” said study author Olivier Lichtarge, MD, PhD, of the Baylor College of Medicine in Houston, Texas.
“As we are witnessing a rise of resistance to artemisinins, these results may help [us in] finding new pathways to successor drugs.”
Dr Lichtarge and his colleagues described this research in Cell.
The team devised a computational method that allows biological information to flow from gene to gene across the supergenomic network.
“The network connects millions of genes from hundreds of species based on their interactions within the organism or based on their ancestral relations between different species,” said study author Andreas Martin Lisewski, PhD, also of the Baylor College of Medicine.
“Normally, computing the flow of functional information would be costly and slow, but we developed a compression method that reduces this gigantic network into one that is much smaller and now computationally tractable. The surprise is that these biological networks are compressible, much like digital data in today’s computers.”
To test their method, the researchers looked at functional predictions of P falciparum. It’s been more than 10 years since this parasite’s genome was fully sequenced, but little is known about the function for most of its genes.
“To better understand this disease, we need to identify more functions of the parasite’s genes,” Dr Lisewski said. “This understanding may eventually help us to stem the rise of drug-resistant malaria, such as the emerging resistance to artemisinins.”
With that in mind, the researchers used their computational method to study EXP1. And they discovered the protein is a membrane glutathione S-transferase that degrades cytotoxic hematin but is inhibited by artesunate.
Credit: Ute Frevert
and Margaret Shear
Researchers say they’ve developed a new computational method to predict the function of disease-causing genes and proteins, and this has enabled an important discovery.
The team used the method to study EXP1, a protein known to be essential to the malaria parasite Plasmodium falciparum, although its exact mechanism has been unclear.
The research revealed that EXP1 enables the parasite to detoxify the main metabolic byproducts it creates in red blood cells.
The researchers also found that EXP1 has a direct role in drug action and susceptibility to artesunate, an important member of the artemisinin drug family.
“Through this multiyear collaborative effort, we now have an improved understanding of the protective molecular mechanisms of the malaria parasite and its drug susceptibility to artesunate,” said study author Olivier Lichtarge, MD, PhD, of the Baylor College of Medicine in Houston, Texas.
“As we are witnessing a rise of resistance to artemisinins, these results may help [us in] finding new pathways to successor drugs.”
Dr Lichtarge and his colleagues described this research in Cell.
The team devised a computational method that allows biological information to flow from gene to gene across the supergenomic network.
“The network connects millions of genes from hundreds of species based on their interactions within the organism or based on their ancestral relations between different species,” said study author Andreas Martin Lisewski, PhD, also of the Baylor College of Medicine.
“Normally, computing the flow of functional information would be costly and slow, but we developed a compression method that reduces this gigantic network into one that is much smaller and now computationally tractable. The surprise is that these biological networks are compressible, much like digital data in today’s computers.”
To test their method, the researchers looked at functional predictions of P falciparum. It’s been more than 10 years since this parasite’s genome was fully sequenced, but little is known about the function for most of its genes.
“To better understand this disease, we need to identify more functions of the parasite’s genes,” Dr Lisewski said. “This understanding may eventually help us to stem the rise of drug-resistant malaria, such as the emerging resistance to artemisinins.”
With that in mind, the researchers used their computational method to study EXP1. And they discovered the protein is a membrane glutathione S-transferase that degrades cytotoxic hematin but is inhibited by artesunate.