BSc (Hons); MRes; PhD
I completed a BSc (Hons) degree in Applied Genetics at the University of Liverpool in 2004, which included an industrial placement year at The Wellcome Trust Sanger Institute in Cambridge. After working as a Research Technician at the Liverpool School of Tropical Medicine, I moved to Edinburgh in 2005 to begin a MRes in Life Sciences based at the MRC Human Genetics Unit, University of Edinburgh. I subsequently undertook a PhD with Prof Andrew Jackson, investigating the function of the mammalian Ribonuclease (RNase) H2 complex.
Mutations in the genes encoding all three of the subunits of human RNase H2 are the most frequent cause of Aicardi-Goutières syndrome (AGS), an autoinflammatory disorder which mimics congenital viral infection. My research focused on the role of RNase H2 and its nucleic acid substrates in innate immunity and succeeded in identifying TLR9 as a specific sensor for intracellular RNA:DNA hybrids in dendritic cells (Rigby et al. 2014). Upon completing my PhD, I worked as a Postdoctoral Researcher in the Jackson lab before moving to Oxford to join the Rehwinkel lab in 2012.
My current research continues to focus on the activation of the innate immune response by nucleic acids, from the initial sensing of viral nucleic acids to the downstream signalling cascades and the antiviral state created. I am also interested in viral antagonists of the innate immune response and study this in the context of Influenza A virus and the RIG-I pathway. I utilise a broad range of techniques to address these questions, from traditional molecular biology methods to mass cytometry and analysis of gene expression at the single cell level. My aim is to achieve a greater insight into the activation of the innate immune system by pathogenic nucleic acids and the consequences this has for the host.
Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling.
Hertzog J. et al, (2018), Eur J Immunol
Ribonuclease H2 mutations induce a cGAS/STING-dependent innate immune response.
Mackenzie KJ. et al, (2016), EMBO J, 35, 831 - 844
RNA degradation in antiviral immunity and autoimmunity
Rigby RE. and Rehwinkel J., (2015), Trends in Immunology, 36, 179 - 188
RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.
Rigby RE. et al, (2014), EMBO J, 33, 542 - 558
SAMHD1-dependent retroviral control and escape in mice
Rehwinkel J. et al, (2013), RETROVIROLOGY, 10, S28 - S28