Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New insights into the survival and transmission strategy of malaria parasites

14.08.2014

HP1 proteins are found in most eukaryotic organisms and are important regulators of gene silencing. In short, HP1 induces heritable condensation of chromosomal regions. As a result genes located within these regions are not expressed. Importantly, since this conformation is reversible HP1-controlled genes can become activated without requiring changes in the underlying DNA sequence.

The team led by Till Voss at the Swiss Tropical and Public Health Institute in collaboration with colleagues from the Nanyang Technological University in Singapore engineered a mutant parasite in which HP1 expression can be shut down at the push of a button. The researchers observed that in HP1-depleted parasites all of the 60 so-called var genes became highly active.

Each var gene encodes a distinct variant of the virulence factor PfEMP1, which is displayed on the surface of the parasite-infected red blood cell. PfEMP1 is a major target of the immune system in infected humans. Individual parasites normally express only one of the 60 different var/PfEMP1 proteins, while keeping all other members silenced.

By switching to another var/PfEMP1 variant the parasite is able to escape existing immune responses raised against previous variants. The new study shows that HP1 protects the PfEMP1 antigenic repertoire from being exposed to the immune system at once.

... more about:
»HP1 »Health »Malaria »PfEMP1 »Plasmodium »malaria »parasite »parasites

The new study shows that HP1 protects the PfEMP1 antigenic repertoire from being exposed to the immune system at once. "This finding is a major step forward in understanding the complex mechanisms responsible for antigenic variation," says Till Voss from the Swiss Tropical and Public Health Institute in Basel. "Furthermore, the tools generated in our study may be relevant for future research on malaria vaccines and immunity."

Lack of HP1 triggers production of malaria transmission stages

Importantly, the study also reveals that parasites lacking HP1 fail to copy their genomes and are hence unable to proliferate. "Initially, we thought all parasites in our culture dish were dead," says Till Voss.

However, it turned out that over 50% of these parasites were fully viable and differentiated into gametocytes, the sexual form of the malaria parasite. Gametocytes are the only form of the parasite capable of infecting a mosquito and therefore a prerequisite to transmit malaria between humans. "Such a high sexual conversion rate is unprecedented. Usually only around 1% of parasites undergo this switch," the researcher explains.

Further experiments show that a master transcription factor triggering sexual differentiation (termed AP2-G) is expressed at much higher levels in parasites lacking HP1. Under normal conditions, HP1 silences the expression of AP2-G and thus prevents sexual conversion in most parasites.

"The switch from parasite proliferation to gametocyte differentiation is controlled epigenetically by a HP1-dependent mechanism," says Till Voss. "This is really exciting. With this knowledge in hand, and with the identification of another epigenetic regulator involved in the same process (published in the same issue of Cell Host & Microbe), we are now able to specifically track the sexual conversion pathway in molecular detail." This may pave the route for the development of new drugs preventing sexual conversion and consequently malaria transmission.

###

The study was financed by the Swiss National Science Foundation, the Singaporean National Medical Research Council, the OPO Foundation, the Rudolf Geigy Foundation and the Boehringer Ingelheim Fonds.

Background: Malaria infection cycle

Malaria is a devastating infectious disease caused by unicellular parasites of the genus Plasmodium. Over 1 billion people worldwide live at high risk of contracting malaria and each year the disease causes more than 200 million clinical cases and 700'000 deaths, mostly among young African children. Plasmodium falciparum, one of five species known to elicit malaria in humans, is responsible for the vast majority of severe and fatal malaria outcomes.

Plasmodium parasites invade red blood cells, undergo intracellular replication, destroy their host cell and release up to 32 daughter parasites ready to infect new red blood cells. Repeated rounds of this vicious cycle lead to a massive expansion of the parasite population in the blood, which is responsible for all malaria-related morbidity and mortality. During each replication cycle a small number of parasites cease to proliferate and differentiate into sexual precursor cells called gametocytes. Only this form is able to infect the mosquito and therefore to transmit malaria to other humans.

Study

Heterochromatin Protein 1 Secures Survival and Transmission of Malaria Parasites. Nicolas M. B. Brancucci, Nicole L. Bertschi, Lei Zhu, Igor Niederwieser, Wai Hoe Chin, Rahel Wampfler, Céline Freymond, Matthias Rottmann, Ingrid Felger, Zbynek Bozdech, and Till S. Voss. Cell Host & Microbe 16, 165-176. 2014

Contact

Prof. Till Voss, Swiss Tropical and Public Health Institute till.voss@unibas.ch, Tel +41 61 284 81 61

Dr. Christian Heuss, Communication, Swiss Tropical and Public Health Institute, christian.heuss@unibas.ch. Tel +41 61 284 86 83

About the Swiss Tropical and Public Health Institute (Swiss TPH)

The Swiss Tropical and Public Health Institute (Swiss TPH) is one of Switzerland's leading public and global health institutions. Associated with the University of Basel, the institute combines research, teaching and service provisions at local, national and international level. Swiss TPH is a public sector organisation and receives around 17% of its budget of approximately 80 million francs from core contributions from the cantons of Basel-Stadt and Basel-Landschaft (10%) and from the federal government (8%). The remainder (82%) is acquired by competing for funds. The Institute has more than 600 employees working in 20 countries.

Christian Heuss | Eurek Alert!
Further information:
http://www.unibas.ch

Further reports about: HP1 Health Malaria PfEMP1 Plasmodium malaria parasite parasites

More articles from Life Sciences:

nachricht Identifying drug targets for leukaemia
02.05.2016 | The Hong Kong Polytechnic University

nachricht A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

Im Focus: New world record for fullerene-free polymer solar cells

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.

Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

Identifying drug targets for leukaemia

02.05.2016 | Life Sciences

Clay nanotube-biopolymer composite scaffolds for tissue engineering

02.05.2016 | Materials Sciences

NASA's Fermi Telescope helps link cosmic neutrino to blazar blast

02.05.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>