Contact
Biography
I carried out my PhD from 1998-2001 with Professor Anne Willis at the University of Leicester on internal ribosome entry site (IRES)-mediated translation. 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. At Stanford, I worked on a liver-specific microRNA, miR-122, and demonstrated that it interacts directly with hepatitis C virus (HCV) RNA and has an essential positive role in HCV replication. I spent the final year of my fellowship 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 to start my own research group, with a focus on understanding miRNA regulation of viral replication. This ran from September 2008 to August 2013. In September 2013 I was appointed Lecturer in the School of Pharmacy. I was promoted to Associate Professor in August 2020.
Teaching Summary
I teach gene therapy and RNA therapeutics as part of the Future Medicines module in year 4 of the MPharm course, PHAR4014.
I convene the Infection and Immunity module in year 2 of the MSci course, PHAR2031. I also teach the virology content on this module.
I also supervise undergraduate research projects, contribute to the Patient Leadership and Management module simulations and OSCEs, and act as a personal tutor.
Research Summary
MicroRNAs (miRNAs) are 21-23 nucleotide (nt) single-stranded RNA molecules that are important regulators of gene expression in a broad range of eukaryotic organisms. They are encoded as part of… read more
Recent Publications
ZHUANG X, MAGRI A, HILL M, LAI AG, KUMAR A, RAMBHATLA SB, DONALD CL, LOPEZ-CLAVIJO AF, RUDGE S, PINNICK K, CHANG WH, WING PAC, BROWN R, QIN X, SIMMONDS P, BAUMERT TF, RAY D, LOUDON A, BALFE P, WAKELAM M, BUTTERWORTH S, KOHL A, JOPLING CL, ZITZMANN N and MCKEATING JA, 2019. The circadian clock components BMAL1 and REV-ERBα regulate flavivirus replication. Nature communications. 10(1), 377 DHIR A, DHIR S, PROUDFOOT NJ and JOPLING CL, 2015. Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs. Nature structural & molecular biology. 22(4), 319-327
School of Pharmacy Building, East Drive, University Park, Nottingham, NG7 2RD
Current Research
MicroRNAs (miRNAs) are 21-23 nucleotide (nt) single-stranded RNA molecules that are important regulators of gene expression 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 hepatitis C virus (HCV) RNA, and that this binding is required for viral replication, a novel mode of action for a miRNA. miR-122 also has biologically important roles in cholesterol and iron metabolism in the liver, and functions as a tumour suppressor.
miRNA and CCR4-NOT function at the endoplasmic reticulum (ER)
As part of a BBSRC-funded grant with Martin Bushell at the Cancer Research UK Scotland Institute, we are investigating how miRNAs and the CCR4-NOT complex work together to regulate gene expression in the cytoplasm and at the ER. To do this, we have generated cell lines which allow targeted protein degradation of CCR4-NOT components by the dTAG method.
miR-122 biogenesis
We are also interested in understanding the biogenesis of miR-122 and other miRNAs. We recently investigated the interplay between splicing and miRNA biogenesis and found that disruption of splicing leads to a broad reduction in miRNA production. We are now investigating the underlying mechanisms.
miRNA function in the inflammatory response
Our third area of research, in collaboration with Dr Cornelia de Moor and Dr Anna Piccinini at the University of Notitngham, focuses on understanding miRNA regulation of mRNAs that are induced at the level of transcription and undergo rapid changes in poly(A) tail length during the inflammatory response.
Therapeutic RNA delivery
In collaboration with Professor Snow Stolnik and Dr Naoto Hori at the University of Nottingham, and Professor Helen Hailes at UCL, we are using state-of-the-art molecular biology approaches to investigate factors that influence efficient RNA delivery into cells for therapeutic purposes.
Group members
Current
Postdoc
Angela Downie (BBSRC-funded)
PhD students
Alfredo Smart (EPSRC CDT)
Merryn Hughes (EPSRC CDT)
Sabesan Anandavijayan (School of Pharmac)
Past
PhD students
Athena Martin
Poppy Winlow
Aimee Parsons
Shoaib Ahmed
Andrew Lewis
Postdocs
Ashley Roberts
Rachel Doidge