Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Locking Parasites in Host Cell Could Be New Way to Fight Malaria

07.04.2009
Researchers at the University of Pennsylvania have discovered that parasites hijack host-cell proteins to ensure their survival and proliferation, suggesting new ways to control the diseases they cause. The study, appearing this week online in Science, was led by Doron Greenbaum, PhD, Assistant Professor of Pharmacology in the Penn School of Medicine.

“Researchers can now develop ways to kill parasites by placing roadblocks in the path they use to destroy their victims,” says Greenbaum. The team discovered that malaria parasites depend upon an enzyme stolen from the host cell for successful infection.

Historically, many researchers have focused on developing ways to keep parasites from entering host cells, but Greenbaum’s group was curious about an alternative route of attack: locking the parasites inside the host cell.

These studies began with Plasmodium falciparum, which causes the most deadly form of human malaria. Each year, the Centers for Disease Control and Prevention report 350–500 million cases of malaria occur worldwide, killing more than a million people. In collaboration with the laboratory of Penn biologist David Roos, PhD, the work was broadened to include Toxoplasma gondii, which causes a parasitic disease called toxoplasmosis, the leading cause of birth defects worldwide and harmful to people with compromised immune systems. The CDC estimates more than 60 million people living in the U.S. carry T. gondii.

“We always suspected that enzymes called proteases might be required to help parasites escape from the infected cell, but had assumed that these enzymes were produced by the parasites themselves. We had never considered that parasites might instead hijack host cell proteases. It's an ingenious system,” says Greenbaum. “Our findings open up whole new window for drug discovery.”

“This work is a triumph of integrative science, combining modern techniques in chemistry, biology, genetics, pharmacology, and genomics," says Roos, the E. Otis Kendal Professor of Biology and Ellison Medical Foundation Senior Scholar of Global Infectious Diseases. Collaborations between the Greenbaum and Roos laboratories have been facilitated by proximity, as these researchers are housed in adjacent space, under the auspices of the Penn Genome Frontiers Institute.

Because Plasmodium and Toxoplasma kill infected cells, they must constantly hop from cell to cell to survive. When parasites burst out of an infected cell, they leave a mess behind, shredding the dense meshwork of proteins comprising the host cell cytoskeleton and breaking the cell apart, causing cell death. But researchers were unsure what proteins the parasites were using as tools to help them break through the walls of the cell.

To observe the behavior of P. falciparum parasites, the team infected human red blood cells, using pharmacological and biochemical evidence to discover that parasites activate the host protease calpain-1. Blocking or removing calpain-1, a calcium regulated protease, left parasites trapped inside the host cell. By adding calpain-1 back into the cell, parasites were able to once again blast free.

Curious to know if the distantly related parasite T. gondii might use the same process, Greenbaum worked with Roos, who has pioneered the use of T. gondii for a wide range of molecular genetic and cellular studies. Infecting mouse fibroblasts with T. gondii, the team used genetic techniques to remove, and restore, calpain activity. They found that in the absence of calpain, parasites could not escape the infected cell, just as they had observed for malaria parasites.

Over the past 40 years, malaria has become increasingly resistant to drugs that once controlled this devastating disease, leading to an alarming increase in deaths. Targeting host proteins rather than the parasite itself might give the parasite less scope to develop resistance, since the parasite doesn't have genetic control over host proteins. Greenbaum plans to continue to explore the viability of calpain as a drug target for antiparasitic drugs.

This work was funded by the Ellison Medical Foundation, National Institute for Allergy and Infectious Diseases, the Ritter Foundation, and the Penn Genome Frontiers institute, and the Penn Institute for Translational Medicine and Therapeutics.

PENN Medicine is a $3.6 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.

Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,700 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

The University of Pennsylvania Health System (UPHS) includes its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top ten “Honor Roll” hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center. In addition UPHS includes a primary-care provider network; a faculty practice plan; home care, hospice, and nursing home; three multispecialty satellite facilities; as well as the Penn Medicine at Rittenhouse campus, which offers comprehensive inpatient rehabilitation facilities and outpatient services in multiple specialties.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Health and Medicine:

nachricht Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>