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Universitaetsklinikum Heidelberg

PARTNER N°	2a
NAME OF INSTITUTION	Heidelberg University Hospital (UKL-HD)
BRIEF DESCRIPTION OF THE TEAM
	Section Clinical Tropical Medicine, Department for Infectious Diseases, Heidelberg University Hospital The Section Clinical Tropical Medicine serves as a clinical reference centre for a wide range of tropical and infectious diseases within the University Hospital and beyond. It runs an outpatient clinic and an inpatient consultation service for patients with tropical / infectious diseases. The research agenda of the Section of Clinical Tropical Medicine includes Arboviral diseases like Dengue virus infections and Zika virus infections, cystic and alveolar echinococcosis, Buruli ulcer, and epidemic bacterial meningitis, funded by the European Commission, Volkswagen Foundation, the German Research Foundation (DFG), and the German Academic Exchange Service (DAAD). The research activities of section are carried out in close cooperation with national and international partners, in Latin America, Africa, and in Asia. Most importantly, the Clinical Tropical Medicine at UKL-HD figures as the coordinating partner of two EC-funded multicentre observational dengue consortia (DENCO, 2005-2009; IDAMS, 2011-2017, ongoing) forming a large network of clinical sites in Asia as well as in Latin America.
KEY CONTACT PERSON(S)
Key scientific contact person 1 (Team leader)
Name	Thomas Jaenisch, MD PhD
Photo
Position in the Institution	Senior Scientist
Email address	thomas.jaenisch@urz.uni-heidelberg.de
Phone number	+49 6221 5638040
Mobile phone number	+49 178 8975302
Postal address	Section Clinical Tropical Medicine Department for Infectious Diseases Heidelberg University Hospital Im Neuenheimer Feld 324 69120 Heidelberg Germany
Role in the Consortium	WP: 1, 2, 9, 10, 11
	Task: 1.1, 1.2, 1.3, 10.1, 10.2, 10.3, 10.4, 11.2
	Sub-task: 10.1.1, 10.2.1, 10.30.1, 10.3.2, 10.3.4, 10.4.1, 10.4.2, 10.4.3, 11.2.1, 11.2.2
	Role: WP1 leader, WP10 leader Thomas Jaenisch and the team at UKL-HD will coordinate work package 1 -“Clinical Science” – focussing on the activties with regard to the large multicentre cohort studies (pregnant women, children, and fever/rash patients), which form the backbone of the project. The multicentre cohort studies will be running in 12-15 sites in Latin America and the Caribbean. In addition, the team at UKL-HD will coordinate the harmonization of the protocols for the ZIKAlliance consortium as well as beyond (e.g. WHO or NIH) and the regulatory procedures including the documentation of all ethical and regulatory documents. Standard Operating Procedures (SOPs) will be developed, harmonized, and issued in English, Spanish, and Portuguese. A customized clinical data base infrastructure will be created and maintained at UKL-HD. Quality control mechanisms for the cohort studies as well as access to the data will be managed centrally for all partners. Finally, data analysis will be carried out by experienced researchers.

PARTNER N°	2b
NAME OF INSTITUTION	Universitätsklinikum Heidelberg (UKL-HD)
BRIEF DESCRIPTION OF THE TEAM
	Work in the Bartenschlager lab centers on the molecular and cell biological aspects related to the fundamental principles of the HCV and DENV replication cycles, the role of innate immunity in DENV replication and spread and in HCV counteracting the innate immune response.
KEY CONTACT PERSON(S)
Key scientific contact person 1 (Team leader)
Name	Prof. Dr. Ralf Bartenschlager
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Position in the Institution	Managing Director
Email address	Ralf.bartenschlager@med.uni-heidelberg.de
Phone number	+49 6221 56 4225
Mobile phone number	--
Postal address	Department of Infectious Diseases, Molecular Virology University Hospital Heidelberg Im Neuenheimer Feld 345 D-69120 Heidelberg Germany
Role in the Consortium	WP: 3
	Task: 3.1
	Sub-task:3.1.2 and 3.1.3
	Role: In the related DENV, mutations in E and especially in NS3 have been reported to promote neurovirulence. The region involved is conserved in ZIKV NS3, suggesting a similar role. Flavivirus interactome studies have identified ~50 cellular proteins interacting with NS3. The interactomes of NS3 from wt and neurovirulent DENV and ZIKV in neuronal vs nonneuronal cells will be compared and cellular protein/NS3 complexes will be isolated to unravel their role in pathogenesis (Bartenschlager, Canard, Van Hemert). The specificity for neuronal tissues, including the brain, and mechanism underlying neuronal pathology will then be addressed (Bartenschlager). This will include cytopathogenicity in neuronal cell lines as well as 3D cell culture systems to account for the complexity of neuronal tissues and pathologies. Host cell factors identified in this way will be further characterized by conventional cell biological assays (Bartenschlager, Van Hemert). This will lay the ground for the discovery of molecules that disrupt NS3‐containinging complexes involved in neuropathogenesis.