Catherine Jopling
BBSRC David Phillips Fellow, Faculty of Science
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Biography
I carried out my PhD from 1998-2001 with Professor Anne Willis at the University of Leicester, where I was involved in research demonstrating that the internal ribosome entry site in the c-myc mRNA allows maintenance of translation during apoptosis. I also identified and characterised internal ribosome entry sites in the related N-myc and L-myc mRNAs.
Following my PhD I obtained a Wellcome Trust International Research Fellowship, which provided funding for me to work as a postdoctoral researcher with Professor Peter Sarnow at Stanford University, USA from 2002-5. MicroRNAs had recently been identified as major regulators of gene expression. My work on a liver-specific microRNA, miR-122, demonstrated that it interacts directly with hepatitis C virus (HCV) RNA and has an essential positive role in HCV replication.
My fellowship provided a further year of funding to return to a UK lab. I spent this year in Professor Richard Jackson's group at the University of Cambridge, where I continued with my previous research. In 2007 I came to Nottingham as part of the RNA Biology Group, and was awarded a BBSRC David Phillips Fellowship. This commenced in September 2008 and provides five years' full funding to start my own research group.
Summary of Academic Career
1998-2001 PhD supervised by Professor Anne Willis, University of Leicester. Identification and characterisation of IRES elements in the N- and L-myc 5'UTRs. Analysis of the continued activity of the c-myc IRES during apoptosis.
2002-2005 Postdoctoral researcher, funded by Wellcome Trust International Research Fellowship, with Professor Peter Sarnow, Stanford University, USA.
2005-2007 Postdoctoral researcher, funded by Wellcome Trust International Research Fellowship, with Professor Richard Jackson, University of Cambridge.
2007-2008 Postdoctoral researcher with Professor Anne Willis.
2008-2013 BBSRC David Phillips Fellow, University of Nottingham.
Research Summary
Hepatitis C virus (HCV) is a hepatotropic, positive sense, RNA virus that infects 2% of the global population. HCV frequently establishes chronic infections that eventually lead to liver cirrhosis… read more
Recent Publications
FLETCHER NF, WILSON GK, MURRAY J, HU K, LEWIS A, REYNOLDS GM, STAMATAKI Z, MEREDITH LW, ROWE IA, LUO G, LOPEZ-RAMIREZ MA, BAUMERT TF, WEKSLER B, COURAUD P, KIM KS, ROMERO IA, JOPLING C, MORGELLO S, BALFE P and MCKEATING JA, 2012. Hepatitis C Virus Infects The Endothelial Cells Of The Blood-Brain Barrier. Gastroenterology. 142(3), 634-643 JOPLING C, 2012. Liver-Specific Microrna-122: Biogenesis And Function. Rna Biology. 9(2), (In Press.)
LEWIS, ANDREW P and JOPLING, CATHERINE L, 2010. Regulation and biological function of the liver-specific miR-122. Biochemical Society transactions. 38(6), 1553-7
Current Research
Hepatitis C virus (HCV) is a hepatotropic, positive sense, RNA virus that infects 2% of the global population. HCV frequently establishes chronic infections that eventually lead to liver cirrhosis and hepatocellular carcinoma. Current treatments are often ineffective and have high associated toxicity, and a greater understanding of viral biology is necessary to develop improved therapies.
MicroRNAs (miRNAs) are 21-23 nucleotide (nt) single-stranded RNA molecules that have recently been identified in a broad range of eukaryotic organisms. They are encoded as part of longer transcripts that undergo successive nuclear and cytoplasmic processing steps to yield a mature miRNA, which functions in association with a complex of proteins known as the miRNP. In animals most miRNAs have been found to function by associating with imperfect complementarity with sites in the 3' untranslated regions (UTRs) of mRNA targets. This results in the repression of gene expression by a process that is not yet fully understood, although inhibition of translation and RNA degradation are both implicated.
Mammalian miRNAs show a high degree of specificity of expression, both by developmental stage and by tissue type. miR-122 is a highly liver-specific miRNA that accounts for 70% of the total miRNA content of the liver. My postdoctoral research showed that miR-122 binds directly to two adjacent sites in the 5'UTR of HCV RNA, and that this binding is required to maintain HCV RNA levels in Huh7 cells. MiR-122 appears to act at the level of viral replication, as translation is unaffected. This positive role in viral replication is a novel mode of action for a miRNA.
My current research focuses on understanding this unusual mechanism of miRNA action in more detail. In particular, this involves analysis of the miR-122 binding site in HCV. This is unusual in its requirement for two miRNA molecules to bind to adjacent sites, and also in that it shows location-dependent activity, as it mediates repression of gene expression when placed in the 3'UTR of a reporter mRNA. The roles of location and structure of miRNA binding sites in determining activity are currently under further investigation.