Unveiling the life-cycles of malarial parasites to aid the routine validation of drugs and live vaccines for the disease.

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Details of the life-cycles of P. falciparum and P.ovale, two of the parasites that cause malaria, are revealed by researchers affiliated with Kawasaki INnovation Gateway at SKYFRONT, Japan. The findings are published in Nature Communications.

Generation of humanized mice engrafted with both human liver tissue and human red blood cells.

Details of the life-cycles of P. falciparum and P.ovale, two of the parasites that cause malaria, are revealed by Hiroshi Suemizu at the Central Institute for Experimental Animals, Kawasaki and researchers affiliated with Kawasaki INnovation Gateway at SKYFRONT, Japan. The findings are published in Nature Communications. The researchers expect the use of humanized mice for malarial studies to aid the routine validation of drugs and live vaccines for the disease.

Further information about science and technology projects at Kawasaki City is available in the Kawasaki SkyFront iNewsletter that highlights research being conducted by scientists and industries affiliated with Kawasaki INnovation Gateway at SKYFRONT (KING SKYFRONT)—the City’s flagship science and technology hub focused on open innovation in the life sciences and environment.

KING SKYFRONT is located on the opposite side of the Tama River that separates Tokyo International Airport (also known as Haneda Airport) and the Tonomachi district of Kawasaki. The Airport plays an important role in the globalization of the innovative activities of scholars, industrialists and City administrators based at KING SKYFRONT.

October 2015 Issue of Kawasaki SkyFront iNewsletter: http://inewsletter-king-skyfront.jp/en/

Unveiling the life-cycles of malarial parasites
Malaria is caused by variants of Plasmodium parasites carried by mosquitoes, and remains a leading cause death worldwide. The strain Plasmodium falciparum triggers a very severe form of malaria, accounting for the majority of deaths. Those people infected with less virulent strain P.ovale may also suffer serious illness, but a key difference is that this particular strain has the ability to ‘lie dormant’ in the body only to reappear months, or even years, later.

Due to the parasites behaving differently in different hosts, it has proven difficult to study the parasites inside the body to verify their precise life-cycle and replication.

Now, for the first time, Valerie Soulard and co-workers at Sorbonne University, Paris, France, with an international team of scientists including Hiroshi Suemizu at the Central Institute for Experimental Animals, Kawasaki, have successfully analyzed the complete life cycle of P.falciparum in the bodies of humanized mice. They also uncovered the stages P.ovale parasites follow inside humanized mice liver cells.
Soulard and her team engrafted mice with both human liver tissues and human red blood cells, to follow the complete development of the P.falciparum parasites from early stages in liver cells, through multiplication to the appearance of mature germ cells in the blood stream.

In addition, the team discovered that, unlike P.falciparum, P.ovale parasites are able to ‘pause’ their development in the liver, maturing weeks later to trigger a relapse of the disease in the patient.
The team hope the further use of humanized mice for malarial studies will aid the routine validation of drugs and live vaccines for the disease, together with further analysis of Plasmodium strains.

Reference and affiliations
Valérie Soulard1,2,3, Henriette Bosson-Vanga1,2,3,4,*, Audrey Lorthiois1,2,3,*,w, Clémentine Roucher1,2,3, Jean- François Franetich1,2,3, Gigliola Zanghi1,2,3, Mallaury Bordessoulles1,2,3, Maurel Tefit1,2,3, Marc Thellier5, Serban Morosan6, Gilles Le Naour7, Frédérique Capron7, Hiroshi Suemizu8, Georges Snounou1,2,3, Alicia Moreno-Sabater1,2,3,* & Dominique Mazier1,2,3,5,*. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Nature Communications 6 (7690) Published 24 July 2015
1. Sorbonne Universités, UPMC Univ Paris 06, CR7, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l’hôpital, F-75013 Paris, France.
2. INSERM, U1135, CIMI-PARIS, 91 Bd de l’hôpital, F-75013 Paris, France.
3. CNRS, ERL 8255, CIMI-PARIS, 91 Bd de l’hôpital, F-75013 Paris, France.
4. Université FHB, UFR SPB, Departement de Parasitologie-Mycologie, BP V 34 Abidjan, Ivory Coast.
5. AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service Parasitologie-Mycologie, Centre National de Référence du Paludisme, 83 Bd de l’hôpital, F-75013 Paris, France.
6. UPMC Univ. Paris 06, INSERM, UMS28, 105 Bd de l’hôpital, F-75013 Paris, France.
7. AP-HP, UPMC Univ. Paris 06, Groupe Hospitalier Pitié-Salpêtrière, Service d’anatomie et cytologie pathologiques, 83 Bd de l’hôpital, F-75013 Paris, France.
8. Central Institute for Experimental Animal, Kawasaki, Kanegawa, Japan.
w Present address: INSERM U1016, CNRS UMRS 8104, Institut Cochin, F-75014 Paris, France.
*corresponding author email address: valerie(dot)soulard(at)upmc(dot)fr

For the first time, researchers in France (with the help of the Central Institute for Experimental Animals, Kawasaki, Japan) have generated humanized mice engrafted with both human liver tissue and human red blood cells. The mice were then used to reveal the full life-cycle of Plasmodium falciparum, and liver stage life-cycle of Plasmodium ovale, two of the parasites that cause malaria.

Video Feature
Mamoru Takase
Senior Manager
Medical Professional Education
Johnson & Johnson K.K. Medical Company
http://inewsletter-king-skyfront.jp/en/video_feature/vol_5/feature01/

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Unveiling the life-cycles of malarial parasites
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About KING SKYFRONT
The Kawasaki INnovation Gateway (KING) SKYFRONT is the flagship science and technology innovation hub of Kawasaki City. KING SKYFRONT is a 40 hectare area located in the Tonomachi area of the Keihin Industrial Region that spans Tokyo and Kanagawa Prefecture and Tokyo International Airport (also often referred to as Haneda Airport).

KING SKYFRONT was launched in 2013 as a base for scholars, industrialists and government administrators to work together to devise real life solutions to global issues in the life sciences and environment.

Website
http://www.city.kawasaki.jp/en/category/132-5-0-0-0-0-0-0-0-0.html

KING SKYFRONT Concept Video
https://www.youtube.com/watch?v=24Y2VFBOD8c&list=PL70Lb7fKyWsjegtd4tBfXQqbRZbeNjqwt&index=2

Further information
Kawasaki City, Japan, Coastal Area International Strategy Office
General Planning Bureau, City of Kawasaki,
1 Miyamoto-cho, Kawasaki-ku, Kawasaki-city, Kanagawa 210-8577, Japan
EMAIL: 20rinkai(at)city(dot)kawasaki(dot)jp

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Naoko Sato
Kawasaki City, Japan
+81 9065213797
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