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Lizzie Horton

DPhil Student

I completed a BSc (Hons) degree in Molecular Biology at the University of Sheffield in 2018. After competing two summer lab placements at the University of Cambridge and University College London, I started my MRes in Biosciences at UCL. My year-long project took place at the Francis Crick Institute, in the Worldwide Influenza Centre. This is one of 6 WHO collaborating centres making up the Global Influenza Surveillance and Response System (GISRS). After the COVID-19 pandemic hit and somewhat disrupted my academic project, I instead helped on the COVID-19 testing pipeline set up at the Francis Crick Institute. After my project finished I stayed in my lab, testing population immunity to novel Influenza A(H3N2) viruses, data from which contributed towards the 2020 Southern Hemisphere Vaccine Composition Meeting.

I am now completing my DPhil in the Rehwinkel lab, with my current research focused on the innate immune response to virus infection. Upon cellular sensing of viral nucleic acids, a signalling cascade ensues, resulting in the production of type I and III interferons. These interferons can then bind to the same cell or neighbouring cells and induce the transcription of interferon-stimulated genes (ISGs) through the JAK-STAT signalling pathway. There are hundreds of ISGs, the protein products of which can induce a cellular anti-viral state through various mechanisms, such as inhibition of virus entry, inhibition of virus replication and inhibition of viral egress. ISGs thus play a vital role in the immune response against viral pathogens. However, while there are hundreds of ISGs, only a few have been well-characterised.

My project aims to characterise the function of selected ISGs through in vitro methods, involving over-expression constructs and knock-out cell lines generated using CRISPR Cas-9 technology, and also through in vivo methods, using knock-out mouse models of infection. From these, I will additionally generate knock-out mouse embryonic fibroblasts (MEFs) and perform infection experiments to characterise the response to different viruses and the kinetics of ISG induction. I utilise a broad range of techniques such as gateway cloning, immunostaining, fluorescence-activated cell sorting, qPCR and virus generation.