Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists at TSRI identify thousands of proteins associated with deadliest form of malaria

04.10.2002


Two scientists at The Scripps Research Institute (TSRI) led a collaborative effort involving 18 researchers at half a dozen laboratories in the United States and Great Britain to determine the "proteome" of the most deadly form of the malaria pathogen - Plasmodium falciparum.

This study, in the current issue of the journal Nature, accompanies an article detailing the completion of a major six-year $17.9-million genome-sequencing effort involving 185 researchers from the United Kingdom, the United States, and Australia that sequenced the entire Plasmodium falciparum genome.

"This is the first instance that I know of where these proteomics studies have gone along side-by-side with the genome sequencing project," says TSRI Cell Biology Professor John Yates, Ph.D, who was the lead scientist involved in the proteomics effort, which identified the proteins in the single-celled Plasmodium that cause malaria.



These efforts will pay huge dividends in global healthcare if even a few of the newly identified proteins lead to the development of new malaria vaccines--and Yates and his colleagues found a total of more than 2,400 proteins.

"We don’t exactly know the function of well over half of the proteins identified--we just know that they are there," says Laurence Florens, Ph.D., who is a research associate at TSRI and the lead author of the study.

Malaria is a nasty and often fatal disease, which may lead to kidney failure, seizures, permanent neurological damage, coma, and death. There are four types of Plasmodium parasites that cause the disease, of which falciparum is the most deadly. (See Supplemental Information: Malaria.)

Knowing which proteins are expressed by Plasmodium falciparum should help scientists understand how the pathogen causes malaria and, with luck, how to thwart it. That was the goal of the proteomics approach taken by Florens and Yates.

Where "genomics" maps the DNA sequence and genes in an organism like Plasmodium falciparum, "proteomics" adds the topographical information to that map by identifying which genes are actually expressed as proteins in the Plasmodium falciparum cells.

More importantly, Florens and Yates also sought to identify which proteins are expressed at which stages of the organism’s lifecycle. This was no small task. Plasmodium falciparum has at least ten distinct stages in its lifecycle, and there is no way of telling which are expressed at each distinct stage of the pathogen’s lifecycle simply by looking at the genes.

But Florens and Yates were able to figure out which proteins were expressed during four different stages (sporozoites, merozoites, trophozoites, and gametocytes) and, thus, which might make good vaccine targets.

Mass Spectrometry and Malaria

The process was basically to take samples of a single isolate of Plasmodium falciparum and grow three of the four different stages in blood in a way that allowed samples to be purified. The fourth stage, the sporozoites, had to be hand-dissected from mosquito salivary glands.

In purifying the samples, Yates and Florens first separated the soluble proteins from the membrane-bound proteins, then digested them (chopped into smaller "peptide" pieces with enzymes), and resolved them using liquid chromatography combined with tandem mass spectrometry.

The instrument detects the pieces and uses sophisticated software that Yates and his colleagues developed previously to search a database of predicted genes to reconstruct most of the proteins in the sample. This technique was particularly useful in this context because it allowed a very large background "noise" of mosquito and human proteins to be subtracted out. The peptides that come from the Plasmodium can be distinguished from those that come from the mosquito or the human.

Furthermore, using the technique, Florens and Yates were able to show not only which genes were expressed in each stage of the Plasmodium falciparum life cycle, but which proteins were membrane-associated, and which were inside the cell--important pieces of information for vaccine design.

One unexpected finding was that a lot of the proteins that were expressed in particular stages "co-localized" in chromosomal gene clusters possibly under the control of common regulatory elements.

Promoters are regions of DNA in front of a gene that "turn on" that gene like a switch and cause it to be expressed as protein. Normally, any given gene will have its own promoter. But Florens and Yates found many different clusters of genes that become expressed together and might be under the control of a single promoter. Florens and Yates believe that this is one of the ways that the pathogen is able to thrive in two different organisms (mosquitoes and humans).

"The switching between stages is something that happens very fast," says Florens, "and [the pathogen] needs a mechanism to express many genes quickly."

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu/

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>