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 Using fragment-based approaches to discover new antibiotics
21.06.2018 | SLAS (Society for Laboratory Automation and Screening)

nachricht Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center

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: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>