Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists at Scripps Research develop new technology to map spread of malarial drug resistance

04.10.2002


Scientists at The Scripps Research Institute (TSRI), Harvard University and the Genomics Institute of the Novartis Research Foundation have found a way to use a relatively new but readily available technology to quickly detect markers in the DNA of the most deadly type of malaria pathogen.

The technology could enable scientists and public health workers to identify the particular strain of malaria during an outbreak and determine if it is drug resistant or not.

"One of the reasons for the resurgence of malaria in Africa and in other parts of the world is the spread of drug resistance," says Assistant Professor Elizabeth Winzeler, Ph.D., who is in the Department of Cell Biology at TSRI and the lead author of the study described in the latest issue of the journal Science.



The work should make it easier to follow the spread of drug resistance around the world and assist health ministries in countries where malaria is a problem to come up with strategies to thwart this spread.

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.

Despite a century of effort to globally control malaria, the disease remains endemic in many parts of the world. With some 40 percent of the world’s population living in these areas, the need for more effective vaccines is profound. Worse, strains of Plasmodium falciparum resistant to drugs used to treat malaria have evolved over the last few decades.

The specter of drug resistance is particularly worrisome because drug resistance can spread through the mating of Plasmodium parasites. And drug-resistant Plasmodium falciparum is more deadly and more expensive to treat. Worse, a drug-resistant strain could lead to the re-emergence of malaria in parts of the world where it no longer exists--except for the occasional imported case--such as the United States.

One of the best tools for fighting any infectious disease is to track it and fight it where it occurs. And one of the best ways to determine the origin of a particular malaria infection and to map the spread of infection is to identify what are called single nucleotide polymorphisms (SNPs).

Polymorphisms, the genetic variability among various isolates of one organism, are responsible for drug resistance in malaria pathogens. In order to follow the spread of drug resistance around the world, one needs to look at how these markers spread as well.

In the past, if scientists wanted to detect SNPs, they would pick one particular gene and sequence it, a time-consuming process. For instance, finding enough polymorphisms to map the gene mutation responsible for resistance to the drug chloroquine, one of the traditional drugs given to patients with malaria, took several years and millions of dollars to determine.

"Now," says Winzeler, "we have demonstrated that you can detect thousands of SNPs all at the same time by doing a simple reaction."

The reaction involves taking DNA from the malaria parasite, chopping it into fragments, and plopping the mixture of fragmented DNA on a "gene chip"-- a glass or silicon wafer that has thousands of short pieces of DNA attached to it.

DNA chips have become a standard tool for genomics research in the last couple of years, and scientists can quite easily put a large number of different oligonucleotide pieces--even all the known genes in an organism--on a single chip. When applying a sample that contains DNA to the chip, genes that are present in the sample will "hybridize" or bind to complementary oligonucleotides on the chip. By looking to see which chip oligonucleotides have DNA bound, scientists know which genes were being expressed in the sample.

But Winzeler used this technology in a novel way. She compared the DNA of Plasmodium falciparum parasites that were resistant to drugs to those that were not and used the differences in the readouts of the gene chips to determine where the SNPs were. Nobody had ever used a gene chip in this way before.

Nor did such a chip exist. Winzeler worked with researchers at the Genomics Institute of the Novartis Research Foundation to create one just for this purpose.

Using putative malaria genes that were identified in the international malaria genome effort, Winzeler took sequences representing 4,000 distinct pieces of these genes on chromosome 2 of the Plasmodium falciparum genome and had a gene chip constructed.

"Having this type of technology and the genome sequenced allows us to look at the genome in a whole new way," says Winzeler. "If you start doing longitudinal studies after you introduce a new drug, you might be able to identify the drug targets or the mechanisms of resistance. If you can start finding the mutations that are associated with drug resistance, then that tells you how to treat patients in the field."

The new technology should also make it possible to do similar research with other organisms, characterizing genetic variability and perhaps conducting population genetics as well. With population genetics, scientists could quickly determine how similar different genomes are to each other and generate estimates of a pathogen’s age or its pattern of spread.

Winzeler found that most of the SNPs were in the DNA of genes that coded for membrane-associated proteins, which is to be expected, since these are the proteins that are on the outer surface of the cell and will endure the greatest selective pressure exerted by host immune systems and drugs.

Significantly, she also found that a number of genes of unknown function were also high in SNPs, which could mean that these unknown genes are also under selective pressure.

"These could represent genes that have important functions in parasite viability or virulence and that warrant further functional characterization," she concludes.

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

More articles from Health and Medicine:

nachricht Custom-tailored strategy against glioblastomas
26.09.2016 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: New welding process joins dissimilar sheets better

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of light metals.
Scientists at the University of Stuttgart have now developed two new process variants that will considerably expand the areas of application for friction stir welding.
Technologie-Lizenz-Büro (TLB) GmbH supports the University of Stuttgart in patenting and marketing its innovations.

Friction stir welding is a still-young and thus often unfamiliar pressure welding process for joining flat components and semi-finished components made of...

Im Focus: First quantum photonic circuit with electrically driven light source

Optical quantum computers can revolutionize computer technology. A team of researchers led by scientists from Münster University and KIT now succeeded in putting a quantum optical experimental set-up onto a chip. In doing so, they have met one of the requirements for making it possible to use photonic circuits for optical quantum computers.

Optical quantum computers are what people are pinning their hopes on for tomorrow’s computer technology – whether for tap-proof data encryption, ultrafast...

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

HLF: From an experiment to an establishment

29.09.2016 | Event News

European Health Forum Gastein 2016 kicks off today

28.09.2016 | Event News

 
Latest News

Researcher creates a controlled rogue wave in realistic oceanic conditions

30.09.2016 | Earth Sciences

Call for Paper – Panacea Green Infrastructure?

30.09.2016 | Event News

Spiral arms: not just in galaxies

30.09.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>