PARTNER N°

23

NAME OF INSTITUTION

Academisch Ziekenhuis Groningen (UMCG) ‐ Netherlands

BRIEF DESCRIPTION OF THE TEAM
 

The academic hospital (also referred to as University Medical Center Groningen) has 10,000 employees and focuses on three important themes: patient

care, scientific research and teaching. The Department of Medical microbiology has over 150 employees and a large number of these people are involved in scientific research.

The UMCG is represented in ZIKAlliance by two researchers from the Department of Medical microbiology: Dr Adriana Tami is involved in WP1 and Prof Jolanda M. Smit in WP3.

The Experimental Virology team, headed by prof. J.M. Smit, studies mosquito‐borne viruses with emphasis on alphaviruses (chikungunya virus and sindbis virus) and flaviviruses (dengue virus, West Nile virus, Zika virus). Our aim is to unravel the molecular interactions between the virus and the host in order to guide the development of safe and efficacious vaccines and anti‐viral drugs. Specifically, we focus on dissecting 1) the cell entry processes of virus articles 2) mechanisms involved in antibody‐mediated neutralization and enhancement of infection, 3) molecular mechanisms by which viruses counteract anti‐viral responses in target cells eg. stress granules and autophagy.

The Epidemiology of Infectious and Tropical Diseases (EPITROP) team led by Dr. A. Tami focuses on the epidemiology, clinical aspects, health-seeking behaviour, pathogen population dynamics and spatial analysis of arboviruses, specifically dengue, chikungunya and zika viruses in South America and the Caribbean. The group is part of the Genomics for Infection Prevention Team headed by Prof. Alex Friedrich (head of Department). The EPITROP group has close collaborations with the University of Carabobo (UC) in Venezuela (Third party of UMCG within ZIKAlliance), of which Dr. Tami is an associate researcher and PI of the WP1 Venezuelan clinical site within the ongoing EU FP7-funded International Research Consortium on Dengue Risk Assessment, Management and Surveillance (IDAMS).

 

KEY CONTACT PERSON(S)

Key scientific contact person 1 (Team leader)

Name

Prof dr J.M. Smit

Photo

 

Position in the Institution

Tenure-track Professor

Email address

Jolanda.smit@umcg.nl

Phone number

 

31-50-3616562

Mobile phone number

n.a.

Postal address

UMCG

Department of Medical Microbiology

Hanzeplein 1

Postbus 30.001
9700 RB Groningen

Internal postcode EB88

 

Role in the Consortium

WP: 3

Task: I

Sub-task: 3.1.1

The route of ZIKV cell entry and membrane fusion will be dissected at the single‐particle level using state‐of‐the‐art microscopy using ZIKV labelled with the fluorescent probe DiD. Membrane fusion of ZIKV will be measured

based on DiD dequenching caused by the dilution of the probe into the endosomal membrane. This approach allows us to characterize the temporal interactions that occur during virus cell binding, entry and membrane fusion. Host proteins important during the early stages of infection, as for example identified in the haploid genetic screen by Brummelkamp, will be fluorescently

tagged and their role in virus cell entry will be dissected by simultaneous tracking of fluorescently labelled proteins and DiD‐labelled virus particles. TIRF microscopy will be used to analyze the role of newly identified receptor molecules in cell attachment, targeting to the portal of entry, and intracellular trafficking. Immunoprecipitation and proximity ligation assays will be conducted to assess if there is a direct interaction between the virus and the identified protein. In parallel, and upon request mode‐of‐action studies will be performed to decipher the antiviral mechanism of drugs and antibodies that are identified during the course of the study.