Welcome to !




















Dr Paul R Young
Department of Microbiology and Parasitology, School of Molecular and Microbial Sciences
University of Queensland
Brisbane, Qld 4072
Email: p.young@uq.edu.au
Tel: +61-7-3365-4646
Fax: +61-7-3365-4620
Homepage: http://smms.uq.edu.au/mypa/academic/young/overview.htm

Research
Our research group is focussed on the molecular biology and immunopathology of medically important viral infections. Currently these involve studies of dengue virus, a serious mosquito-borne disease in many tropical countries, and Respiratory Syncytial Virus (RSV), a major cause of hospitalization of children with respiratory infections. The primary goals of our research are the development of vaccine and anti-viral strategies for the control of infections as well as a clearer understanding of the pathogenesis of severe disease.
Our interest in protease research centres on the NS3 protease of the flaviviruses, dengue and West Nile virus as a target for both antiviral drug design and as the focus for generation of attenuated viruses as vaccine candidates. The NS3 protease (a serine protease) is absolutely essential for viral replication and as such is an ideal target for inhibitor design. We were the first to generate an active recombinant form of the two-component flavivirus NS3 protease suitable for in vitro assays. These assays have subsequently been applied to the screening of small compound libraries and to gaining insight’s into key catalytic and substrate-interacting residues through site-directed mutagenesis. Crystallization trials for structure determination of both dengue and WN proteases with and without complexed inhibitors are ongoing. We are also currently assessing the effect of changes in key residues in NS3 and its cofactor NS2B, on viral replication through mutagenesis of full-length infectious clones.
Collaborations
Prof David Fairlie Assoc. Prof. Jenny Martin
Prof Luiz Neto
Assoc. Prof. Alex Khromykh
Dr Roy Hall
Publications
Leung D, Schroeder K, White H., Fang N-X, Stoermer M J, Abbenante G, Martin J L, Young P, Fairlie D P. Activity Of Recombinant Dengue 2 Virus NS3 Protease In The Presence Of NS2B Cofactor, Small Peptide Substrates, And Inhibitors Journal of Biological Chemistry, 2001, 276, 45762-45771.

Arakaki T L, Fang N-X, Fairlie D P, Young P R and Martin J L. Catalytically active dengue virus NS3 protease forms aggregates that are separable by size exclusion chromatography. Protein Expression and Purification, 2002 25, 241-247.

Brinkworth R I, Fairlie D P, Leung D. and Young P R. Homology model of the dengue virus NS3 protease: putative interactions with both substrate and NS2B cofactor. Journal of General Virology, 1999 80, 1167-1177.





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