Current Research Programmes:
1. Virus-host interactions and the development of antiviral therapies
The aim is to develop a fundamental understanding of the molecular interactions between (+ve) ssRNA viruses and their hosts. Research is focused on members of the family Tetraviridae, a group of small insect RNA viruses as a model system for studying the biology of (+ve) ssRNA viruses that infect insects. In particular, we are interested in how these viruses redirect the metabolism of their host cells to support virus replication and in the case of Providence virus, the establishment of persistent infections in tissue culture cell lines. Research projects in the group include: (i) fundamental studies on the subcellular localization of virus replication and the interactions between viral and host proteins that result in the establishment of viral replication factories (ii) characterisation of the translational control systems employed by tetraviruses to regulate expression of their gene products and the role these systems play in virus replication and (iii) understanding the mechanisms of viral RNA encapsidation during virus particle assembly and the development of drug and gene-delivery technologies.
Walter, CT, Tomasicchio, M, Hodgson, V, Hendry, DA, Hill, MP and RA Dorrington*. 2008. Characterisation of a succession of small insect viruses in a wild South African population of Nudaurelia cytherea capensis. SA J Sci 104, 147-152 Walter et al 2008
Tomasicchio, M, Venter, PA, Gordon, KHJ, Hanzlik, TN and RA Dorrington* 2007. Induction of apoptosis in Saccharomyces cerevisiae results in the spontaneous maturation of tetravirus procapsids in vivo. J Gen Virol; 88: 1576-1582 Tomasicchio et al 2007
2. Structure-function studies on Eukaryotic Initiation Factor 5A (eIF-5A)
One of the major challenges in the development of anticancer drugs is to be able to target only the tumour cells and avoid toxic side effects on normal cells. Ideally, such drugs should either target unique properties of the tumour cells, or they should inhibit cell division without killing the cell, thus establishing control of tumour cell proliferation. One such potential target is the eukaryotic initiation factor 5A (eIF-5A), a highly conserved RNA binding protein found in all eukaryotes. eIF5A is the only protein known to undergo post-translational modification of a highly conserved lysine residue to form hypusine. Mutations in this lysine residue or inhibition of enzymes that catalyze the hypusination pathway result in cell cycle arrest in the G1 phase making inhibition of the protein a target for the development anti-cancer drug development. The aim of our research is to exploit a yeast experimental system to understand how the structure of eIF-5A relates to its function in the cell. The information gathered from these studies could lead to new opportunities for developing drugs that inhibit the function of this protein.
Gentz PM, Blatch GL, Dorrington RA (2009) Dimerisation of the yeast eukaryotic translation initiation factor 5A requires hypusine and is RNA dependent. FEBS J. 276 (3):695-706. Gentz et al 2009
Medical Research Council of South Africa (2008 -2010); National Research Foundation of South Africa (Unlocking the Future, Economic Competitiveness programs) (2004 – 2009); Rhodes University Research Niche Area (2007-2009); Rhodes University Joint Research Committee Grant (2008).