Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists reveal molecular secrets of the malaria parasite

10.01.2005


Groundbreaking research project may help boost vaccine development

In an innovative project with implications for malaria vaccine development, scientists have used genomics, proteomics and gene expression studies to trace how malaria parasites evolve on a molecular level as they move between their hosts and insect vectors.
That focus on the parasites’ complex life cycle is helping researchers understand when different genes switch on and off as the pathogens metamorphose through seven different life stages. In turn, that molecular-level data may benefit biomedical scientists who are identifying new targets for vaccines that would impede the parasite during stages when it is particularly vulnerable to intervention.


"We hope this project will help vaccine researchers find the best targets against malaria," says scientist Neil Hall, the first author of the paper that appears in the January 7th issue of Science. "The study’s findings will help scientists identify parasite genes that are interacting with the host as well as new gene targets for vaccines that aim to prevent parasite transmission in the mosquito."

The study highlights the genes in four malarial species that evolve rapidly because of "selective pressures" in the stages of their life cycles in their mosquito vectors and in their mammalian hosts. Malaria parasites undergo three stages in their mosquito vectors, three stages in their vertebrate hosts and a sexual development stage during which the parasite is transmitted between vector and host.

The Science paper represents the culmination of four years of cooperative work by scientists at several research institutes, including: the Wellcome Trust Sanger Institute in the U.K., where the sequencing and genome annotation was performed on two species of rodent malaria (Plasmodium chabaudi and P. berghei); the University of Leiden in the Netherlands and Imperial College in England, where scientists carried out gene expression studies; and The Institute for Genomic Research (TIGR), in Maryland, where scientists did a comparative analysis of the two draft genomes with those of the first rodent malaria parasite to be sequenced, Plasmodium yoelii.
The first author of the paper is Hall, a TIGR Assistant Investigator who did most of his work on this project while in his previous position as a bioinformatics scientist at Sanger. He was also the first author of the 2002 study —led by scientists at TIGR, Sanger, and Stanford University —that presented the complete genome of Plasmodium falciparum, the deadliest human malarial parasite.

Hall says the Science paper is important because:

  • The study takes an "evolutionary approach" to exploring how the Plasmodium genome has evolved. By comparing four sequenced genomes (the human malaria P. falciparum and the rodent malarias P. yoelii, P. chabaudi and P. berghei), the scientists found that the major differences between the malarial species are found in the virulence factors (which are at the chromosome ends) while the "housekeeping" genes are almost totally unchanged.

  • Researchers showed that the parasite genes evolve most rapidly when they are expressed in the mammal hosts (human/mouse). That may represent a mechanism by the parasites to repulse the attack of the host’s immune system.

  • For the first time, scientists were able to study the protein expression of the parasite in the mosquito vector. Researchers hope this will shed light on how the mosquito and parasite interact, and perhaps will lead to new ways of controlling the parasite in the vector.

  • Hall and scientists in Leiden identified evidence of an unusual method of gene regulation (called post transcriptional regulation) at the transition between the vertebrate host and the mosquito. That motif regulates proteins that are switched on as the parasite enters the mosquito.

Hall’s group identified the gene regulation by comparing the genes expressed in the sexual stage transcriptome with the proteomes of both the sexual stage and a developmental stage in the mosquito. Several genes were identified for which transcripts were detected in the sexual stage but with protein products specific to the mosquito stage, indicating delayed translation of transcripts from these genes.

Hall says that gene-regulation motif "is particularly interesting because these proteins, expressed early in the mosquito, are the target of transmission-blocking vaccines" —that is, vaccines which raise antibodies that attack the parasite in the vector. (Such antibodies are in the "blood meal" and still work for an hour or so after the mosquito bites).

Another TIGR scientist who played an important role in the project is Associate Investigator Jane Carlton, who had led the sequencing of P. yoelii. At TIGR, Carlton constructed a composite of all three rodent genome sequences (P. yoelii, P. berghei, P. chabaudi) by aligning them against the P. falciparum genome to create a whole-genome synteny map of the four species. In collaboration with Leiden University researchers, Carlton’s group was then able to generate maps that compare the degrees of similarity among genes on P. falciparum chromosomes and its rodent-malaria counterparts.

"The paper is significant on many levels, including the integration of draft genome sequence data with microarray and protein expression data," says Carlton. "This project also shows the power of collaboration between international institutes with different areas of expertise. It was remarkably productive collaboration."

Robert Koenig | EurekAlert!
Further information:
http://www.tigr.org

More articles from Life Sciences:

nachricht For a chimpanzee, one good turn deserves another
27.06.2017 | Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPIMIS)

nachricht New method to rapidly map the 'social networks' of proteins
27.06.2017 | Salk Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Touch Displays WAY-AX and WAY-DX by WayCon

27.06.2017 | Power and Electrical Engineering

Drones that drive

27.06.2017 | Information Technology

Ultra-compact phase modulators based on graphene plasmons

27.06.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>