Dr Caroline Knox
Biography
- 1988 - 1993
PhD (University of the Witwatersrand)
- 1994 - 1997
Postdoctoral Fellow, Hadassah Medical School, Jerusalem, Israel
- 1997 - 2003
Postdoctoral Fellow, University of St Andrews, Scotland
- 2004 - present
Senior lecturer
Head, Microbiology discipline
Department of Biochemistry, Microbiology and Biotechnology
Rhodes University
Academic Teaching
- Microbiology II: Microbial genetics, Introductory Virology
- Microbiology III: Eukaryotic Cell Biology, Advanced Virology, Immunology
- Microbiology Honours: Animal cell culture, Emerging Infectious Diseases, Picornavirus biology
Research
Picornavirus-host cell interactions Picornaviruses are an economically important group of pathogens. Diseases caused by picornaviruses such as poliomyelitis, hepatitis A and human rhinitis pose significant threats to human health, as does Foot-and-Mouth disease to the beef and dairy industries in many countries. Although many reports describe the epidemiology and pathogenesis of such diseases, the molecular mechanisms by which picornaviruses interact with components of host cells they infect are poorly understood. Identifying such mechanisms will not only provide new knowledge of Picornavirus biology, but also may contribute to the urgently required development of more effective disease control strategies. My research utilises a model picornavirus, Theiler’s murine encephalomyelitis virus (TMEV), which is non-infectious for humans and livestock, and for which we have successfully developed a cell-culture infection system. This provides an opportunity for us to compare the effects on subcellular structure and function induced by the individual expression of non-structural viral proteins with those induced by the virus during replication. The research is being conducted in collaboration with institutes in the United Kingdom.
Virus discovery Acute infantile gastroenteritis is a significant health problem in southern Africa and worldwide, leading to high morbidity and mortality. Many cases are of unknown etiology. Rotaviruses are prime causative agents of gastrointestinal infections in southern Africa, but routine screening of stool samples from infants with acute gastroenteritis at the MRC Diarrhoeal Pathogen Research Unit based at MEDUNSA has revealed that a significant number of specimens test negative for this pathogen each year, suggesting the possible presence of novel or unrecognised viral pathogens. Newly-identified human viruses genetically related to members of the Cardiovirus genus (thought to contain only rodent viruses) have recently been recognised as ubiquitous human enteric pathogens, providing evidence for the alarming evolution of picornaviral (and other viral) genomes. Enteric viruses are present in untreated or polluted water sources and are associated with waterborne transmission, thereby posing a significant health risk. Moreover, vaccine and disease eradication programmes rely on a thorough knowledge of the microbial diversity associated with infections. Accordingly, there is an urgent need to assess the presence of existing and emerging viruses and their possible role in disease. Access to a high throughput sequencing facility will allow (i) an in-depth analysis of viral species present in clinical and environmental samples and (ii) efficient and cost-effective sequencing of novel, full-length viral genomes.
Genetic characterisation of baculovirus for the control of insect pests Lepidopteran insects such as False codling moth (FCM) and Diamondback moth (DBM) are serious pests of citrus and other crops in Africa and worldwide, with considerable financial impact. Conventional pest management programmes rely on chemical insecticides which, although effective, can have negative environmental implications and lead to the development of pest resistance. Alternative methods of control are urgently required and there is increasing promise in the use of entomopathogenic microbes as biocontrol agents, specifically a group of naturally occurring insect viruses belonging to the baculovirus family. Two baculovirus products namely, Cryptogran® (River Bioscience, South Africa) and Cryptex® (Andermatt Biocontrol, Switzerland) have been formulated and registered for the control of FCM in South Africa. There is a need to develop similar products targeting DBM and other insect pests. Insect resistance to the viral strain used in contemporary biocontrol products complicates their effectiveness, necessitating a search for genetic variants with greater virulence and pathogenicity. A standard technique used in our laboratory to analyse genetic variation of virus isolates involves restriction enzyme analysis of viral DNA, which is tedious and time-consuming. Access to a high throughput DNA sequencing facility will allow fast and efficient sequencing of baculovirus genomes and will facilitate identification and characterisation of novel baculoviruses that can be isolated and formulated as biocontrol agents against a variety of insect pests. This project is being conducted in collaboration with Professor Martin Hill (Head, Department of Entomology, Rhodes University) and Dr Sean Moore (Citrus Research International, South Africa).
Recent publications
Knox, C., Luke, G.A., Blatch, G.L. and Pesce, E.-R. Heat Shock Protein 40 (Hsp40) plays a key role in the virus life-cycle. Virus Res. DOI: 10.1016/j.virusres.2011.06.013.
Mutsvunguma, L., Edkins, A.L., Luke, G.A., Blatch, G.L., Knox, C. 2011. Theiler's Murine Encephalomyelitis virus infection induces a redistribution of heat shock proteins 70 and 90, and is inhibited by geldanamycin and Novobiocin. Cell Stress and Chaperones. DOI 10.1007/s12192-011-0262-x.
Jauka, J., Mutsvuguma, l., Boshoff, A., Edkins, A.L., Knox, C. 2010. Localisation of Theiler's Murine Encephalomyelitis virus protein 2C to the Golgi apparatus using antibodies generated against a peptide region. Journal of Virological Methods 168: 162-169.
Short, J.S., Knox, C., Dorrington, R.A.2010. Subcellular localisation and live cell imaging of the Helicoverpa armigera stunt virus 1 replicase in mammalian and Spodpoptera frugiperda cells. J. Gen. Virol. 91: 1514-1523.
Murray, L., Luke, G., Ryan, M. D., Wileman, T., Knox, C. 2009. Amino acid substitutions within the 2C coding sequence of Theiler’s Murine Encephalomyelitis virus alter virus growth and affect protein distribution. Virus Res. 144: 74-82.
Moffat, K., Knox, C., Howell, G., Clarke, S.J., Yang, H., Belsham, G.J., Ryan, M.D., Wileman, T. 2007. Inhibition of the secretory pathway by Foot-and-Mouth Disease Virus 2BC protein is reproduced by coexpression of 2B with 2C, and the site of inhibition is determined by the subcellular location of 2C. J. Virol. 81: 1129-1139.
Moffat, K., Howell, G., Knox, C., Belsham, G.J., Monaghan, P., Ryan, M.D., Wileman, T. 2005. Effects of Foot-and-Mouth Disease virus non-structural proteins on the structure and function of the early secretory pathway: 2BC but not 3A blocks ER to Golgi transport. J. Virol. 79: 4382-4395.
Knox, C., Moffat, K., Ali, S., Ryan, M. D., Wileman, T. 2005. Foot-and-mouth disease virus replication sites form next to the nucleus and Golgi apparatus, but exclude marker proteins associated with host membrane compartments. J. Gen. Virol. 86: 687-696.
Knox, C., Sass, E., Neupert, W., Pines, O. 1998. Import into mitochondria, folding and retrograde movement of fumarase in yeast. J. Biol. Chem. 273(40): 25587-25593.
Schonberger, O., Knox, C., Bibi, E., Pines, O. 1996. Split invertase polypeptides form functional complexes in the yeast periplasm in vivo. PNAS 93: 9612-9617.
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Current vacancies
MSc/PhD Positions starting in 2012 Masters and PhD positions will be available in the beginning of 2012 for students who have an interest in virus-host interactions. The project is funded by the Medical Research Council of South Africa. Candidates should have a BSc Honours degree in one of the life sciences, and an interest in molecular biology, cell biology, virology and protein biochemistry. To comply with the funding conditions, candidates need to be South African citizens or permanent residents. If you are interested, please email your full CV to Dr Caroline Knox.
Contact details
Department of Biochemistry, Microbiology and Biotechnology Rhodes University Grahamstown 6140 South Africa Tel: +27 46 6038023 Fax: +27 46 6037576 Email: caroline.knox@ru.ac.za
