Prof. Willy J. M. Spaan (scientific coordinator of SARS-DTV; w.j.m.spaan@lumc.nl) and his research team at the Department of Medical Microbiology of Leiden University Medical Center, the Netherlands, have studied the molecular biology of positive-stranded RNA viruses, including coronaviruses and other nidoviruses, for almost 25 years. The Department has an active research program on viral genome structure and expression, virus evolution, pathogenesis, diagnosis of virus infections, and vaccine development, carried out by a multidisciplinary team of molecular biologists, biochemists, bio-informaticians, and (clinical) virologists. The Department is part of the LUMC Center of Infectious Diseases, which also includes the Departments of Parasitology and Infectious Diseases, and the centralized Clinical Diagnostic Laboratory. Research infrastructure includes BSL1, BSL-2, and BSL-3 facilities. The section Molecular Virology of the Department has published many key publications on replication, genome expression and evolution of Coronaviruses and other nidoviruses. Willy Spaan is acting chairman of the Department of Medical Microbiology, chairman of the LUMC Center of Infectious Diseases, and chairman of one of the five Divisions of LUMC. He was coordinator of two FP5 research programs and is coordinator of a FP6 subnetwork of the viRgil Network of Excellence (http://www.virgil-net.org/). He also chairs the Coronavirus study group of the International Committee on the Taxonomy of Viruses (ICTV; http://www.ncbi.nlm.nih.gov/ICTVdb/index.htm).

Prof. Eric J. Snijder (deputy coordinator of SARS-DTV and leader of the Molecular Targets work package; e.j.snijder@lumc.nl) has studied nidovirus molecular biology since 1985. Following a Ph.D. from Utrecht University on the replication of toroviruses, a subgroup of the coronavirus family, he joined Willy Spaan in Leiden in 1990. Since then, the arterivirus family of the Order Nidovirales has been one of his prime research interests. His group developed the arterivirus prototype EAV into one of the best-studied nidovirus models in terms of molecular biology and pioneered nidovirus reverse genetics, following the development of the first nidovirus infectious cDNA clone in Leiden in 1996. Important contributions were made to the elucidation of the mechanism of nidovirus RNA synthesis, structure and function of the nidovirus replicase and replication complex, and our understanding of nidovirus evolution. His research is supported by grants from the Council for Chemical Sciences of the Netherlands Organisation for Scientific Research (NWO) and the European Commission. Eric Snijder chairs the ICTV Arterivirus study group, was the principle organizer of the 2003 triennial Symposium on Nidoviruses, and initiated research on the SARS-Coronavirus in Leiden within weeks after the identification of the novel agent.

Prof. Alexander E. Gorbalenya (a.e.gorbalenya@lumc.nl) has studied a wide range of RNA viruses by different methods since 1975. First in leading research centers of Russia/USSR, subsequently at the National Cancer Institute (USA), before joining the LUMC faculty in 2002. His studies have led to major discoveries in the molecular biology and evolution of numerous viruses, including nidoviruses, flaviviruses, picornaviruses, alphaviruses, birnaviruses. His pioneering bio-informatics analysis of the replicase of coronaviruses and their relatives produced models that have guided experimental research during the past 15 years. To facilitate interdisciplinary research on RNA viruses and to integrate the results obtained, he established a productive network of collaborations with leading virologists in many European countries, North America and the Southern Hemisphere. Alexander Gorbalenya serves as a member of the ICTV study groups on coronaviruses and arteriviruses and is a Steering Committee member and Section Leader in the EC-funded VIZIER project (http://www.vizier-europe.org/) on the structural genomics of the replicative enzymes of RNA viruses.

Ing. Jessika Zevenhoven-Dobbe (j.c.zevenhoven-dobbe@lumc.nl) has been involved in LUMC nidovirus research since 1995. As a research technician, she has worked with both coronaviruses and arteriviruses in a variety of research lines, including reverse genetics, antibody production, the biochemical dissection of nidovirus infections, and cell biological studies. Since 2003, she is involved in SARS-Coronavirus research, including BSL-3 activities with live virus, and she contributes to various topics within the SARS-DTV research program, including the establishment and maintenance of the SARS-DTV BioBase.

Dr. Sjoerd van den Worm (s.h.e.van_den_worm@lumc.nl) studied chemistry at Leiden University. In 2004, he also obtained his Ph.D. from Leiden University for his thesis on RNA-protein interactions in single-stranded RNA phages. Since March 2004, he is involved in LUMC SARS-coronavirus research as a postdoctoral fellow. Since its start in October 2004, he is working on the SARS-DTV project full-time, with a special interest in reverse genetics and the functional dissection of coronavirus replicase functions. His experimental work includes in vitro and in vivo biochemical studies on individual coronavirus nonstructural proteins and the replication complex as a whole, and also activities with live virus in the LUMC BSL-3 facility. Sjoerd van den Worm is the primary person responsible for the SARS-DTV DataBase and BioBase, which have been established at LUMC in the context of SARS-DTV work package 4 .

In addition to the above people directly involved in SARS-DTV, several other researchers are involved in LUMC SARS-Coronavirus research.

Jeroen Corver, René Broer, and Peter Bredenbeek are working with Willy Spaan on the SARS-Coronavirus spike protein.
Martijn van Hemert is collaborating with Sjoerd van den Worm and Eric Snijder on the development of assays for nidovirus in vitro RNA synthesis and the dissection of the nidovirus replication complex.
Kèvin Knoops, Henk Koerten, and Mieke Mommaas of the LUMC Center for Electron Microscopy (Department of Molecular Cell Biology) are collaborating with Eric Snijder on the cell biology of the replication complex of nidoviruses, including SARS-Coronavirus.

Selected publications of Partner 1:

Seybert. A., Posthuma, C.C., van Dinten, L.C., Snijder, E.J., Gorbalenya, A.E., and Ziebuhr, J. 2005. A complex zinc finger controls the enzymatic activities of nidovirus helicases. J. Virol. 79:696-704. (http://dx.doi.org/doi:10.1128/JVI.79.2.696-704.2005)
Gorbalenya, A.E., Snijder, E.J., and Spaan, W.J.M. 2004. Severe acute respiratory syndrome coronavirus phylogeny: toward consensus. J. Virol. 78:7863-7866. (http://dx.doi.org/doi:10.1128/JVI.78.15.7863-7866.2004)
Ivanov, K.A., Thiel, V., Dobbe, J.C., van der Meer, Y., Snijder, E.J., and Ziebuhr, J. 2004. Multiple enzymatic activities associated with severe acute respiratory syndrome coronavirus helicase. J. Virol.78:5619-5632. (http://dx.doi.org/doi:10.1128/JVI.78.11.5619-5632.2004)
Snijder E.J., Bredenbeek P.J., Dobbe J.C., Thiel V., Ziebuhr J., Poon L.L., Guan Y., Rozanov M., Spaan W.J., and Gorbalenya A.E. 2003. Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage. J. Mol. Biol. 331:991-1004. (http://dx.doi.org/doi:10.1016/S0022-2836(03)00865-9)
Pasternak A.O., van den Born E., Spaan W.J.M., and Snijder E.J. 2001. Sequence requirements for RNA strand transfer during nidovirus discontinuous sub-genomic RNA synthesis.EMBO J. 20:7220-7228. (http://dx.doi.org/doi:10.1093/emboj/20.24.7220)
Tijms M.A., van Dinten L.C., Gorbalenya A.E., and Snijder E.J. 2001. A zinc finger-containing papain-like protease couples sub-genomic mRNA synthesis to genome translation in a positive-stranded RNA virus. Proc. Natl. Acad. Sci. USA. 98:1889-1894. (http://dx.doi.org/doi:10.1073/pnas.041390398)
Ziebuhr J., Snijder E.J., and - Gorbalenya A.E. 2000. Virus-encoded proteinases and proteolytic processing in the Nidovirales.J Gen Virol. 81:853-879. (http://vir.sgmjournals.org/cgi/content/full/81/4/853)