Malaria remains one of the most deadly infectious diseases. Yet, how Plasmodium, the malaria parasite, regulates its infectious cycle has remained an enigma despite decades of rigorous research.
But now a research team led by a cell biologist at the University of California, Riverside has identified a mechanism by which Plasmodium intensively replicates itself in human blood to spread the disease.
"If this mechanism can be stopped," said Karine Le Roch, an assistant professor of cell biology and neuroscience, who led the research, "Plasmodium replication would cease or be severely inhibited, thus controlling the spread of malaria."
In the cells of eukaryotes, such as the unicellular Plasmodium and humans, DNA, which can be as long as two meters, is closely packed to fit into the cell's tiny nucleus. Huge complex proteins called nucleosomes facilitate this DNA compaction so that eventually the DNA is coiled in an ordered manner to form chromosomes.
Made up of histone, a kind of protein, the nucleosomes are repeating units around which the double helix of DNA gets wrapped and vast amounts of genetic information get organized.In trying to understand how the malaria parasite multiplies in red blood cells, Le Roch's team found that in Plasmodium a kind of "histone crash" takes place – a massive breakdown of histone that explains how the parasite can replicate extensively its DNA and coding gene in human red blood cells.
While in humans such eviction of nucleosomes is specific to only some sections of the DNA strand and performed only when needed, in Plasmodium the situation is vastly different.
Le Roch's experiments in the lab show that 18 hours after Plasmodium enters a red blood cell, a huge eviction of nucleosomes occurs in the Plasmodium DNA. Gene transcription throughout the genome follows; after multiplication into up to 32 daughter cells, the newly-formed parasites are ready to exit the red blood cell and invade new ones about 18 hours later.
"We found in our experiments that histones are massively evicted everywhere in the Plasmodium genome, resulting in most of the Plasmodium genes to be transcribed at once," Le Roch said. "If we can find a candidate enzyme that can regulate this massive histone eviction, we could halt or greatly limit Plasmodium replication."
Study results appear this month in the journal Genome Research.
"Dr. Le Roch's findings document a global mechanism mediating significant changes in gene expression as the parasites transition through developmental stages in the human hosts," said Anthony A. James, a distinguished professor of microbiology & molecular genetics and molecular biology & biochemistry at UC Irvine, who was not involved in the research. "As well as being a major basic discovery, this provides a basis for probing the mechanisms for novel drug development."
Le Roch obtained her master's degree in parasitology at the University of Lille II and the University of Oxford, in 1997. She completed her doctorate in 2001 at the University of Paris VI, working on the cell cycle regulation of Plasmodium. In 2001, she joined the Scripps Research Institute, San Diego, Calif., to carry out the functional analysis of the Plasmodium genome using microarray technologies. In 2004, she joined the Genomics Institute of the Novartis Research Foundation, Calif., where she developed the malaria drug discovery program. She joined UCR in 2006.
Le Roch was joined in the study by Nadia Ponts (the first author of the research paper), Elena Harris, Jacques Prudhomme, Glenn Hicks and Stefano Lonardi at UCR; and Ivan Wick, Colleen Eckhardt-Ludka and Gary Hardiman at UC San Diego.
UCR startup funds supported the study.
The University of California, Riverside (www.ucr.edu) is a doctoral research university, a living laboratory for groundbreaking exploration of issues critical to Inland Southern California, the state and communities around the world. Reflecting California's diverse culture, UCR's enrollment of about 18,000 is expected to grow to 21,000 students by 2020. The campus is planning a medical school and has reached the heart of the Coachella Valley by way of the UCR Palm Desert Graduate Center. The campus has an annual statewide economic impact of more than $1 billion.
A broadcast studio with fiber cable to the AT&T Hollywood hub is available for live or taped interviews. To learn more, call (951) UCR-NEWS.
Iqbal Pittalwala | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
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...
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...
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...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy