Nav: Home

Fighting malaria through metabolism

March 23, 2017

EPFL scientists have fully modeled the metabolism of the deadliest malaria parasite. The model offers unprecedented tools for developing a new generation of antimalarial therapies to overcome drug resistance.

Many of the malaria parasites develop resistance to drugs. A promising strategy is to target the parasite's metabolism, but it has proven very complicated to connect to their genetics. EPFL scientists have now developed the first ever mathematical model of a malaria parasite that accurately integrates its genetics and metabolism, opening a whole new way of treating the disease. The model is based on the deadliest of the malaria parasites, Plasmodium falciparum, and is published in PLoS Computational Biology.

There have been intensive research efforts to map out and target metabolic enzymes of the Plasmodium parasites. But their metabolism has proven to be versatile and complex, and integrating all existing data on the parasites' genetics to their metabolism is challenging.

A new model of malaria parasites' metabolism

The lab of Vassily Hatzimanikatis at EPFL, with colleagues at Geneva and Bern, has now developed a new mathematical model of the malaria parasite P. falciparum. The model connects the experimental data from both genetics and metabolomics, which is the study of all the metabolic processes of an organism and maps out all of its metabolites.

Malaria parasites infect various cells through their life cycle, displaying different points of vulnerability at each life stage. However, there has not been a comprehensive attempt to investigate the enzymes that are consistently vulnerable.

The scientists studied P. falciparum but instead looked at the way the parasites produce and use energy for their metabolic reactions. This approach can help identify which metabolic functions are essential at each stage of the infection, and which are energetically coupled through key metabolites.

The scientists could therefore model, for the first time, the bioenergetics of the metabolism of P. falciparum, predicting with unprecedented accuracy which genes are indispensable for every biological function in the parasite.

By integrating metabolomics and genetics data, the model reveals the complex interactions between gene products, reactions, and metabolites in the parasite, and identifies potential mechanisms to target with drugs.

"The design of efficient antimalarial drugs that target the parasites and not the patient's metabolism requires an in-depth understanding of the mechanisms that make a particular enzyme essential," says Anush Chiappino-Pepe, the Ph.D. student who carried out the study at Hatzimanikatis' lab. "So mathematical modeling of the parasite's metabolism becomes a very powerful tool."

The EPFL scientists will continue to improve the model with genetics and metabolomics data generated by the MalarX.ch consortium, which involves the University Geneva and Bern, and the Wellcome Trust Sanger Institute. They aim to reveal the mechanisms behind host-pathogen interactions and gain insight into the physiology of the parasite while it is dormant.

This work included a contribution from the University of Geneva (Faculty of Medicine). It was funded by SystemsX.ch (MalarX), the Swiss

-end-

National Science Foundation (SNSF), EPFL and the University of Geneva.

Reference

Anush Chiappino-Pepe, Stepan Tymoshenko, Meriç Ataman, Dominique Soldati-Favre, Vassily Hatzimanikatis. Bioenergetics-based Modeling of Plasmodium falciparum Metabolism Reveals its Essential Genes, Nutritional Requirements, and Thermodynamic Bottlenecks. PLoS Computational Biology 23 March 2017.

Scientific contacts

Professor Vassily Hatzimanikatis (Lead researcher)
Tel. +41 21 69 39870, +41 21 69 39891
vassily.hatzimanikatis@epfl.ch

Anush Chiappino Pepe, EPFL (First author of paper)
Tel. +41 21 69 39869
anush.chiappinopepe@epfl.ch

Press contact

Nik Papageorgiou (EPFL Press Office)
Tel. +41 21 69 32105
n.papageorgiou@epfl.ch

Ecole Polytechnique Fédérale de Lausanne

Related Parasites Articles:

Deciphering plant immunity against parasites
Nematodes are a huge threat to agriculture since they parasitize important crops such as wheat, soybean, and banana; but plants can defend themselves.
Malaria parasites 'walk through walls' to infect humans
Researchers have identified proteins that enable deadly malaria parasites to 'walk through cell walls' -- a superpower that was revealed using the Institute's first insectary to grow human malaria parasites.
Scientists analyze dispersal of parasites by birds in the Americas
An international study investigates transmission of microorganisms that cause malaria and other diseases from migratory to resident avian species.
What's the buzz on bee parasites?
Published today in the open-access journal GigaScience is an article that presents the genome sequence and analysis of the honey bee parasitic mite T. mercedesae.
Major drug initiatives are best way to curb threat from parasites
Large-scale programmes to treat a life-threatening disease could improve the health of millions despite concerns about their long-term effects, a study suggests.
Promoting parasites
Hiroshima University scientists have identified a new species of parasite infecting an invasive freshwater fish on the subtropical island of Okinawa, Japan.
Sunflower pollen protects bees from parasites
Solitary mason bees specializing on sunflower pollen were not attacked by a common brood-parasitic wasp, which lays eggs in the nests, where its larvae kill bee eggs and eat their pollen provisions.
Trouble with parasites? Just migrate!
The researchers developed a model to explore whether combating infection could, in theory, be a potential benefit of migration.
Bird genomes contain 'fossils' of parasites that now infect humans
In rare instances, DNA is known to have jumped from one species to another.
Common pesticides kill amphibian parasites, study finds
A recent study by Jessica Hua, assistant professor of biological sciences at Binghamton University, and colleagues, explored the effects of six commonly used pesticides on two different populations of a widespread parasite of amphibians.

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: Radiolab

Oliver Sipple
One morning, Oliver Sipple went out for a walk. A couple hours later, to his own surprise, he saved the life of the President of the United States. But in the days that followed, Sipple's split-second act of heroism turned into a rationale for making his personal life into political opportunity. What happens next makes us wonder what a moment, or a movement, or a whole society can demand of one person. And how much is too much?  Through newly unearthed archival tape, we hear Sipple himself grapple with some of the most vexing topics of his day and ours - privacy, identity, the freedom of the press - not to mention the bonds of family and friendship.  Reported by Latif Nasser and Tracie Hunte. Produced by Matt Kielty, Annie McEwen, Latif Nasser and Tracie Hunte. Special thanks to Jerry Pritikin, Michael Yamashita, Stan Smith, Duffy Jennings; Ann Dolan, Megan Filly and Ginale Harris at the Superior Court of San Francisco; Leah Gracik, Karyn Hunt, Jesse Hamlin, The San Francisco Bay Area Television Archive, Mike Amico, Jennifer Vanasco and Joey Plaster. Support Radiolab today at Radiolab.org/donate.
Now Playing: TED Radio Hour

Future Consequences
From data collection to gene editing to AI, what we once considered science fiction is now becoming reality. This hour, TED speakers explore the future consequences of our present actions. Guests include designer Anab Jain, futurist Juan Enriquez, biologist Paul Knoepfler, and neuroscientist and philosopher Sam Harris.