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‘Essential’ genes could be targeted to treat malaria

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Red blood cell infected with malaria parasites (blue)

More than 2000 genes are “essential” for the malaria parasite Plasmodium falciparum, according to research published in Science.

Researchers identified 2680 genes that appear necessary for growth and survival during P falciparum’s asexual blood stage.

The researchers therefore believe these genes could be viable therapeutic targets for P falciparum malaria.

“Malaria parasites are extremely technically difficult to manipulate and sequence, and, until this study, only a few of P falciparum’s essential genes had been determined,” said study author Iraad Bronner, of the Wellcome Sanger Institute in Hinxton, UK.

“Our technological advances enabled us to identify all the essential genes in P falciparum—the first time this has been possible for a human malaria parasite.”

To determine which genes P falciparum needs to survive and thrive, the researchers disrupted the parasite’s genes.

The team used piggyBac-transposon insertional mutagenesis to inactivate genes at random and then used DNA sequencing technology to identify which genes were affected.

The researchers made more than 38,000 mutations, then looked for genes that hadn’t been changed, implying they were essential for P falciparum to survive and grow.

This revealed 2680 non-mutable genes, about 1000 of which are conserved in all Plasmodium species and have unknown functions.

“What our team has done is develop a way to analyze every gene in this parasite’s genome,” said study author John H. Adams, PhD, of the University of South Florida in Tampa.

“Using our genetic analysis tools, we’re able to determine the relative importance of each gene for parasite survival. This understanding will help guide future drug development efforts targeting those essential genes.”

The researchers noted that the proteasome pathway had a “high ratio of essential to dispensable genes,” and recent research has linked this pathway to resistance to artemisinin combination therapy.

“We need new drug targets against malaria now more than ever, since our current antimalarial drugs are failing,” said study author Julian C. Rayner, PhD, of Wellcome Sanger Institute.

“This is the first large-scale genetic study in the major human malaria parasite P falciparum and gives a list of 2680 essential genes that researchers can prioritize as promising possible drug targets. We hope this functional genomics approach will help to speed up the pipeline to develop new treatments for this devastating disease.”

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Image from NIAID
Red blood cell infected with malaria parasites (blue)

More than 2000 genes are “essential” for the malaria parasite Plasmodium falciparum, according to research published in Science.

Researchers identified 2680 genes that appear necessary for growth and survival during P falciparum’s asexual blood stage.

The researchers therefore believe these genes could be viable therapeutic targets for P falciparum malaria.

“Malaria parasites are extremely technically difficult to manipulate and sequence, and, until this study, only a few of P falciparum’s essential genes had been determined,” said study author Iraad Bronner, of the Wellcome Sanger Institute in Hinxton, UK.

“Our technological advances enabled us to identify all the essential genes in P falciparum—the first time this has been possible for a human malaria parasite.”

To determine which genes P falciparum needs to survive and thrive, the researchers disrupted the parasite’s genes.

The team used piggyBac-transposon insertional mutagenesis to inactivate genes at random and then used DNA sequencing technology to identify which genes were affected.

The researchers made more than 38,000 mutations, then looked for genes that hadn’t been changed, implying they were essential for P falciparum to survive and grow.

This revealed 2680 non-mutable genes, about 1000 of which are conserved in all Plasmodium species and have unknown functions.

“What our team has done is develop a way to analyze every gene in this parasite’s genome,” said study author John H. Adams, PhD, of the University of South Florida in Tampa.

“Using our genetic analysis tools, we’re able to determine the relative importance of each gene for parasite survival. This understanding will help guide future drug development efforts targeting those essential genes.”

The researchers noted that the proteasome pathway had a “high ratio of essential to dispensable genes,” and recent research has linked this pathway to resistance to artemisinin combination therapy.

“We need new drug targets against malaria now more than ever, since our current antimalarial drugs are failing,” said study author Julian C. Rayner, PhD, of Wellcome Sanger Institute.

“This is the first large-scale genetic study in the major human malaria parasite P falciparum and gives a list of 2680 essential genes that researchers can prioritize as promising possible drug targets. We hope this functional genomics approach will help to speed up the pipeline to develop new treatments for this devastating disease.”

Image from NIAID
Red blood cell infected with malaria parasites (blue)

More than 2000 genes are “essential” for the malaria parasite Plasmodium falciparum, according to research published in Science.

Researchers identified 2680 genes that appear necessary for growth and survival during P falciparum’s asexual blood stage.

The researchers therefore believe these genes could be viable therapeutic targets for P falciparum malaria.

“Malaria parasites are extremely technically difficult to manipulate and sequence, and, until this study, only a few of P falciparum’s essential genes had been determined,” said study author Iraad Bronner, of the Wellcome Sanger Institute in Hinxton, UK.

“Our technological advances enabled us to identify all the essential genes in P falciparum—the first time this has been possible for a human malaria parasite.”

To determine which genes P falciparum needs to survive and thrive, the researchers disrupted the parasite’s genes.

The team used piggyBac-transposon insertional mutagenesis to inactivate genes at random and then used DNA sequencing technology to identify which genes were affected.

The researchers made more than 38,000 mutations, then looked for genes that hadn’t been changed, implying they were essential for P falciparum to survive and grow.

This revealed 2680 non-mutable genes, about 1000 of which are conserved in all Plasmodium species and have unknown functions.

“What our team has done is develop a way to analyze every gene in this parasite’s genome,” said study author John H. Adams, PhD, of the University of South Florida in Tampa.

“Using our genetic analysis tools, we’re able to determine the relative importance of each gene for parasite survival. This understanding will help guide future drug development efforts targeting those essential genes.”

The researchers noted that the proteasome pathway had a “high ratio of essential to dispensable genes,” and recent research has linked this pathway to resistance to artemisinin combination therapy.

“We need new drug targets against malaria now more than ever, since our current antimalarial drugs are failing,” said study author Julian C. Rayner, PhD, of Wellcome Sanger Institute.

“This is the first large-scale genetic study in the major human malaria parasite P falciparum and gives a list of 2680 essential genes that researchers can prioritize as promising possible drug targets. We hope this functional genomics approach will help to speed up the pipeline to develop new treatments for this devastating disease.”

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