Navigation Links
New insights into the survival and transmission strategy of malaria parasites
Date:8/13/2014

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.

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.


'/>"/>

Contact: Christian Heuss
christian.heuss@unibas.ch
41-612-848-683
Swiss Tropical and Public Health Institute
Source:Eurekalert

Related biology news :

1. New insights into cloud formation
2. Research on flavanols and procyanidins provides new insights into how these phytonutrients may positively impact human health
3. Battle of the sexes offers evolutionary insights
4. Study provides new insights into structure of heart muscle fibers
5. Study offers new insights into the effects of stress on pregnancy
6. Cell biology -- new insights into the life of microtubules
7. Yak genome provides new insights into high altitude adaptation
8. Zebrafish provide insights into causes and treatment of human diseases
9. Feces fossils yield new insights into ancient diets and thrifty genes
10. Piglets in mazes provide insights into human cognitive development
11. The ENCODE Project publishes new genomic insights in special issue of Genome Research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/17/2017)... NXT-ID, Inc. (NASDAQ: NXTD ) ("NXT-ID" ... its 2016 Annual Report on Form 10-K on Thursday April 13, ... ... the Investor Relations section of the Company,s website at http://www.nxt-id.com ... http://www.sec.gov . 2016 Year Highlights: ...
(Date:4/11/2017)... , April 11, 2017 Crossmatch®, a ... authentication solutions, today announced that it has been ... Research Projects Activity (IARPA) to develop next-generation Presentation ... "Innovation has been a driving force ... program will allow us to innovate and develop ...
(Date:4/11/2017)... NXT-ID, Inc. (NASDAQ:   NXTD ) ("NXT-ID" or ... independent Directors Mr. Robin D. Richards and Mr. ... the company,s corporate governance and expertise. ... Gino Pereira , Chief Executive Officer said," ... and benefiting from their considerable expertise as we move forward ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... BARBARA, CALIFORNIA (PRWEB) , ... October 10, 2017 ... ... management, technological innovation and business process optimization firm for the life sciences and ... BoxWorks conference in San Francisco. , The presentation, “Automating GxP Validation ...
(Date:10/9/2017)... N.C. (PRWEB) , ... October 09, 2017 , ... At ... announced Dr. Christopher Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, ... Stubbs was a member of the winning team for the 2015 Breakthrough Prize in ...
(Date:10/7/2017)... ... October 06, 2017 , ... ... launched its ProxiMeta™ Hi-C metagenome deconvolution product, featuring the first commercially available ... bioinformatics software to perform Hi-C metagenome deconvolution using their own facilities, supplementing ...
(Date:10/5/2017)... YORBA LINDA, CA (PRWEB) , ... October 05, 2017 , ... ... tech innovators, engineers, and scientists from around the world, is giving back to cancer ... shirt sold in October. , Now through October 31, shoppers can use promo ...
Breaking Biology Technology: