MedicineWorld.Org
Your gateway to the world of medicine
Home
News
Cancer News
About Us
Cancer
Health Professionals
Patients and public
Contact Us
Disclaimer

From Medicineworld.org: Defeating Malarial Parasite Defense

SARS main Acute bacterial meningitis SARS news updates  


Do You Read All Of Our Cancer Blogs?

Do You Read All Of Blogs?
Do you read all of the blogs published by medicineworld.org? Many of our bloggers are busy keeping you updated on the various health related topics. We publish the following blogs at this time.

Cancer blog: I manage the cancer blog with lots of help and support form other bloggers. Through this cancer blog my friends and I try to bring stories of hope for patients with cancer. The cancer blog often republishes important blog posts from other cancer related blogs at Medicineworld.org. If you are searching for a blog that covers wide variety of cancer topics, this may be the one for you.

Breast cancer blog: Breast cancer blog is run by Emily and other bloggers and they bring you the latest stories, news and events that are related to breast cancer. Increasing awareness about breast cancer among women and in the general population is the main goal of this breast cancer blog.

Lung cancer blog: Lung cancer blog is managed by Scott with the help of other bloggers. Through this blog Scott and his friends constantly remind the readers about the dangers of smoking. It's a never-ending struggle against this miserable disease with which a social stigma of smoking is associated.

Colon cancer blog: Colon cancer blog is run by Sue and other bloggers. Sue brings a personal touch to the colon cancer blog since her mother died of colon cancer few years ago. She writes about stories, research news and advances in treatment related to colon cancer.

Prostate cancer blog: Prostate cancer is the most common cancer among American men. American Cancer Society estimates that over 230,000 new cases of prostate cancer occur in the United state every year. This important blog about prostate cancer is run by Mark and other bloggers. This blog brings news, stories, and other personal observations related to prostate cancer.

Medicineworld.org publishes a diabetes watch blog and this blog is run by JoAnn other bloggers. This diabetes watch blog brings you the latest in the field of diabetes. This includes personal stories, advances in diagnosis and treatment, and other observations about diabetes. Improving awareness about diabetes is an important mission of this group.

Janet      

Defeating Malarial Parasite Defense


Defeating Malarial Parasite Defense
The world's deadliest malaria parasite, Plasmodium falciparum, sneaks past the human immune system with the help of a wardrobe of invisibility cloaks. If a person's immune cells learn to recognize one of the parasite's a number of camouflage proteins, the surviving invaders can swap disguises and slip away again to cause more damage. Malaria kills an estimated 2.7 million people annually worldwide, 75 percent of them children in Africa.

Howard Hughes Medical Institute (HHMI) international research scholars in Australia have determined how P. falciparum can turn on one cloaking gene and keep dozens of others silent until each is needed in turn. Their findings, published in the December 28, 2005, issue of Nature, reveal the mechanism of action of the genetic machinery thought to be the key to the parasite's survival.

A DNA sequence near the start of a cloaking gene, known as the gene's promoter, not only turns up production of its protein, but also keeps all other cloaking genes under wraps, according to Alan Cowman and Brendan Crabb, HHMI international research scholars at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, and their co-authors. "The promoter is all you need for activation and silencing," Cowman said. "It's the main site of action where everything is happening."

Malaria parasites enter human blood from infected mosquitoes. The organisms invade and promptly remodel red blood cells. They decorate the surface of the cells they occupy with a protein called PfEMP1, made by the var gene family.

Using this versatile surface protein, the parasite evades the host's immune system using two basic strategies. First, the protein sticks infected red blood cells to the blood vessel lining, removing the infected cells from circulation, where they would probably be destroyed.

But the protein cannot protect the parasite from patrolling immune cells, which eventually detect the invader and recruit troops to fight it. So, during a malaria infection, a small percentage of each generation of parasites switches to a different version of PfEMP1 that the body has never seen before. In its new disguise, P. falciparum can invade more red blood cells and cause another wave of fever, headaches, nausea, and chills.

"It's like a leopard being able to change its spots," Cowman said. "New forms come up, and the immune system beats them down again. Because of this a lot of people think you need five years of constant exposure to malaria in its different disguises to gain immunity."

A number of children do not survive malaria long enough to develop immunity. And without continuous exposure, hard-won immunity may disappear. For example, adults in Papua New Guinea who move to work in the mining industry, which is in mountainous regions that are mosquito-free, lose their immunity within a short time, he said.

The diverse genetic sequences of the 60 var cloaking genes all code for remarkably similar protein structures, the malaria researcher added. The genes are generally found at the ends of P. falciparum's 14 chromosomes, eventhough some of them cluster in internal regions.

In April 2005, Cowman, Crabb, and his colleagues showed that var genes are regulated by the chromosome packaging, which unwraps one gene to be expressed at a time and literally packs away the inactive genes. In chromosomes, DNA can be encased so securely by some proteins that other proteins cannot access the nucleic acid for transcription, a process known as epigenetic silencing.

In their new paper, the scientists show that the activation of a var gene promoter is all it takes to trigger both the production of that gene's protein and the epigenetic silencing of the 59 other var genes. As in a prior study, they found that the physical location of the promoter within the nucleus seems to make a difference. The genetic activity occurred at the edge of the nucleus, with the activated promoter surrounded by chromosome ends containing silenced var genes.

To do this research, the researchers had to master the difficult technique of cloning large DNA sequences with a var promoter attached to various genes, inserting them into plasmid vectors, and introducing them into red blood cells infected by malaria parasites.

In one experiment, they set up a system where var gene expression could be studied using drug selection rather than the immune pressure that is normally needed to select variants in the field. Using this system they found that the information mandatory for switching var genes on and off was contained within a promoter and that when active this could silence all of the var genes in the parasite.

"This is the first time anyone has actually been able to infiltrate an antigenic variation program," Cowman said. "We forced the cell to switch our gene on and others off." Their system can be used to study blood samples from people in the field to determine how they gain immunity over time.

Kirk Deitsch's lab at Cornell University found that a piece of shared DNA-discarded in the process of translating the protein from its genetic instructions-was a key regulator of var gene silencing and activation. The HHMI scientists confirmed that this gene segment caused tighter packaging for the silenced genes, but they also showed that it wasn't vital.

The scientists are continuing to disassemble the var gene machinery, piece by piece. They want to identify the proteins that unpack and activate the promoter region and learn more about the other proteins in the nuclear compartment that make it the prime spot for var gene activation. Eventually, they think their work may lead to new types of therapies that interfere with the parasite's immune evasion strategies.


Source: Howard Hughes Medical Institute


Did you know?
The world's deadliest malaria parasite, Plasmodium falciparum, sneaks past the human immune system with the help of a wardrobe of invisibility cloaks. If a person's immune cells learn to recognize one of the parasite's a number of camouflage proteins, the surviving invaders can swap disguises and slip away again to cause more damage. Malaria kills an estimated 2.7 million people annually worldwide, 75 percent of them children in Africa.

Medicineworld.org: Defeating Malarial Parasite Defense

SARS Main| SARS Abroad| SARS and Goverment| SARS Information in different languages| Media about SARS| Physicians resources for SARS| Reference information for SARS| Updates on SARS|

Copyright statement
The contents of this web page are protected. Legal action may follow for reproduction of materials without permission.