Professor Lisa Roberts

Biography

Bsc (Hons) Medical microbiology, University of Birmingham (1990)

Worked in industry for Procter & Gamble from 1990-1994

PhD University of Kent/BBSRC Institute for Animal Health “Internal initiation of protein synthesis on picornavirus RNA” (1998)

Research Interests

My research is focused on understanding the molecular mechanisms of virus/host cell interactions during RNA virus infections. We have a particular interest in members of the Caliciviridae family but also in viruses belonging to the Picornaviridae (and related insect viruses).

Caliciviruses are important pathogens of man (e.g noroviruses which cause gastroenteritis outbreaks) and animals (e.g feline calicivirus which causes cat 'flu). The human are the major cause of non-bacterial gastroenteritis in adults worldwide, being associated with over 85% of all non-bacterial gastroenteritis outbreaks in Europe. Norovirus outbreaks cause particular problems in areas where close person-to-person contact cannot be avoided e.g. in hospitals, cruise ships and military camps, with hospital outbreaks alone costing the NHS greater than £100 million per year. Despite this huge impact and disease burden, vaccines or antiviral therapies which may control norovirus outbreaks are yet to be developed. Hence, we and others have begun to use molecular methods to analyse the virus life cycle to allow the design of rational strategies for antiviral intervention and development of attenuated vaccines.

Currently little is known about the molecular mechanisms of calicivirus pathogenesis, mainly due to the lack of an efficient cell culture system for the human viruses. We therefore use murine norovirus and feline calicivirus as model viruses to study virus/host interactions..

Initiation of protein synthesis on calicivirus mRNAs

We are interested in translational control during calicivirus infection. Specifically, we are studying the mechanism of viral mRNA translation and the effect of virus infection on host cell translation. We have recently shown that the VPg protein attached to the 5' end of the viral RNA acts a proteinaceous cap substitute and binds to eIF4E, part of the cap-binding complex. This is a novel mechanism for animal RNA viruses but is similar to that used by some plant potyviruses. Current work focuses on defining other initiation factors, and .trans-acting factors, required for initiation on calicivirus RNA.

Mechanism of calicivirus cell entry

We are currently investigating the mechanism of cell entry used by murine norovirus. We are using specific inhibitors of endocytic pathways to dissect the route of entry, with a view to identifying ways to inhibit this first step in the replication cycle.

Translation initiation on picornavirus RNA

The picornaviruses are a large family of viruses which cause important disease in man (e.g. poliovirus) and animals (e.g. foot and mouth disease virus). Unlike most cellular mRNAs, translation of picornavirus mRNA is not dependent on a 5' cap structure, but the 5' untranslated region (UTR) of the picornavirus genome contains an Internal Ribosome Entry Site (IRES) which directs a cap-independent initiation of translation.

We are studying the mechanism of internal initiation, particularly the role of RNA-RNA interactions and RNA-protein interactions in this process.

Recently, we have focused on the mechanism of translation initiation in a group of insect picorna-like viruses. We have shown that the 5' UTR of Rhopalosiphum padi virus (RhPV) contains an IRES element which functions in insect, mammalian and plant translation systems. The ability of this IRES to function in insect and plant systems has clear application to insect and plant protein expression systems, allowing expression of two proteins in a cell at the same time. We are currently looking at further characterisation of the IRES (and others from related insect picornaviruses), and their utility in protein expression systems.

We are also interested in the IRES elements from several recently-sequenced picornaviruses, such as avian encephalomyelitis virus (AEV) and Seneca Valley virus (SVV). The 5’ UTRs of these picornaviruses contain an IRES element with strong sequence similarity to the hepatitis C virus IRES. We are currently probing the function of this and related IRES elements.

Publications

Publications (last 5 years)

1. Willcocks, M M, Gomwalk, Z., Royall, E., Bakhshesh, M., Belsham, G. J., Idamakanti,m N., Burroughs, K. D., Reddy, P. S., Hallenbeck, P. L. and Roberts, L. O. Structural Features of the Seneca Valley Virus Internal Ribosome Entry Site (IRES) Element: a Picornavirus with a Pestivirus-Like IRES. J. Virol. 85: 4452-4461.

2. Wiley, M, Roberts, L, Adelman, Z and Myles, K. Double Subgenomic Alphaviruses Expressing Multiple Fluorescent Proteins using a Rhopalosiphum padi Virus Internal Ribosome Entry Site Element PLoS ONE Article number e13924 10 Nov 2010.

3. Gerondopoulos, A, Jackson, T, Monaghan, P and Roberts, L O. (2010). Murine norovirus-1 cell entry is mediated through a non-clathrin, dynamin and cholesterol dependent pathway. J Gen. Virol. 91: 14281438.

4. Karakasiliotis, I, Vashist, S, Bailey, D, Roberts, L, Sosnovtsev, S and Goodfellow, I. (2010). Polypyrimidine Tract binding protein functions as a negative regulator of feline calicivirus translation. PLoS One 5(3): e9562. doi:10.1371/journal.pone.0009562.

5. Belsham, G J, Nielsen, I, Normann, P, Royall, E & Roberts, L O. (2008) Monocistronic mRNAs containing defective hepatitis C virus-like picornavirus internal ribosome entry site elements in their 5’untranslated regions are efficiently translated in cells by a cap-dependent mechanism. RNA 14, 16711680.

6. Bakhshesh, M., Groppelli, E., Willcocks, M. M., Royall, E., Belsham, G. J. and Roberts, L. O. (2008). The Picornavirus Avian Encephalomyelitis Virus possesses a Hepatitis C Virus-like internal ribosome entry site (IRES) element. J. Virol. 82: 19932003.

7. Wiley, M. R., Roberts, L. O., Adelman, Z. N., and Myles, K. M. (2008). Dicistronic expression of multiple fluorescent proteins from a double subgenomic alphavirus. Amer. J. Trop. Med. & Hygiene. Amer Soc Trop Med & Hygiene. 79: 94-94.

8. Monie, T. P., Perrin, A. J., Birtley, J. R., Sweeney, T. R., Karakasiliotis, I., Chaudhry, I., Roberts, L. O., Matthews, S., Goodfellow, I. G. and Curry, S. (2007). Structural insights into the transcriptional and translational roles of Ebp1. EMBO J. 26: 3936-3944.

9. Groppelli, E., Belsham, G. J. and Roberts, L. O. (2007) Identification of minimal sequences of the Rhopalosiphum padi virus 5’ untranslated region required for internal initiation of protein synthesis in mammalian, plant and insect translation systems. J Gen. Virol. 88: 15831588.

10. Karakasiliotis, I., Chaudhry, Y., Roberts, L. O., and Goodfellow, I. G. (2006). Feline calicivirus replication: requirement for polypyrimidine tract-binding protein is temperature-dependent. J Gen Virol. 87: 33393347.

11. Chaudhry, Y., Nayak, A., Bordeleau, M. E., Tanaka, J., Pelletier, J., Belsham, G. J., Roberts, L. O., Goodfellow, I. G. (2006) Caliciviruses differ in their functional requirements for eIF4F components. J Biol. Chem. 281 (35): 2531525325.

12. Pijlman, G. P., Roode, E. C., Fan, X., Roberts, L. O., Belsham, G. J., Vlak, J. M. and van Oers, M. M. (2006) Stabilized baculovirus vector expressing a heterologous gene and GP64 from a single bicistronic transcript. Journal of Biotechnology 123, 1321.

13. Natoni, A., Kass, G. E. N., Carter, M. J. and Roberts, L. O. (2006) The mitochondrial pathway of apoptosis is triggered during feline calicivirus infection. J. Gen. Virol. 87, 357361.

Recent reviews

Roberts, L. O. and Groppelli, E.J. An atypical IRES within the 5' UTR of a dicistrovirus genome. (2009).Virus Research 139: 157165.

Roberts, L. O. and Holcik, M. (2009). RNA structure: new messages in translation, replication and disease. EMBO Reports 10, 449453.

Goodfellow, I. G. and Roberts, L. O. (2008). Translation initiation factor eIF4E. Intl. J. Biochem. and Cell Biol. 40: 26752680.

Teaching

I teach on the following modules at undergraduate level;

Level 2 Animal Virology

Level 2 Pathology and Medicine

Level 2 Current topics in microbiology

Level 2 Key Skills

Level 3 Control of infectious disease

And the following modules at MSc level;

Virology

Molecular biology

Management skills

Departmental Duties

Dean of the Faculty of Health and Medical Sciences