Dr Laura N Jeffreys

Post Doctoral Research Associate

I obtained my BSc (Hons) in Biochemistry from the University of Lancaster during which time I completed several lab-based projects including working in the Wolfson Centre for Personalised Medicine (UoL) and within a Cancer Research laboratory (LU). I completed my PhD at the Manchester Institute of Biotechnology (MIB) within the University of Manchester. During my PhD I developed many high-value oxy-pharmaceuticals using a bacterial P450 enzyme. P450 enzymes are found in all Kingdoms of life and are important for xenobiotic metabolism and steroid production. Using a number of techniques including LC-MS, LC-MS/MS, NMR and synthetic biology approaches we generated known human metabolites for many highly prescribed drugs using our bacterial variant, such as pioglitazone and gemfibrozil. We also generated many structures of our protein with and without ligands to further understand its highly dynamic nature using X-ray crystallography, IMS MS and HDX-MS techniques. During my PhD I also worked within the University of Manchester’s Intellectual Property Department (UMIP) gaining commercialisation experience, particularly for pharmaceutical and graphene-based products. Before starting at LSTM I worked at the contract research organisation Gentronix, testing compounds such as fragrances, pharmaceuticals and pesticides for cytotoxic effects.

Many treatments currently exist to treat tuberculosis, particularly active forms of this devastating disease. Recently, several inhibitors of the electron transport chain (ETC) have been approved for clinical use. By starving the cells of energy using ETC inhibitors, in isolation or in combination therapies, there is a potential to treat drug-susceptible, drug-resistant and latent forms of TB. Recent success stories, such as Q203 (Telacebec) and bedaquiline, have highlighted the advantages of using ETC inhibitors in clinical settings. However, the ETC of tuberculosis is easily modulated by the pathogen leading to resistance and reduced bactericidal effects. We are investigating current and novel compounds to treat TB using combination approaches.

Recently, we have been working on drug discovery for COVID-19 in addition to my tuberculosis research. I helped to develop a high-throughput cell-based plaque assay allowing for the screening of >1000 compounds against SARS-CoV-2 in under 10-months from design to completion. From this work many FDA-approved drugs were identified with favourable anti-SARS-CoV-2 profiles. I was awarded a DCF grant in 2021 to work on the project entitled “Elucidating the mechanisms of action of new chemical entities and repurposed drugs against SARS-CoV-2” to investigate compounds identified from our screening work. In addition to my research, I teach on several courses including DLTROP202 and DLTROP204 and am an active member of the biological safety committee, Athena Swan self-assessment team and early career researchers (ECR) committee.

Member (MRSB) of the Royal Society of Biology (RSB)

Member of the Biochemical Society

Associate Fellow of the HEA (AFHEA)

Selected publications

  • Laura N. Jeffreys, Kamila J. Pacholarz, Linus O. Johannissen, Hazel M. Girvan, Perdita E. Barran, Michael W. Voice, Andrew W. Munro,Characterization of the structure and interactions of P450 BM3 using hybrid mass spectrometry approaches, Journal of Biological Chemistry, Volume 295, Issue 22, 2020, Pages 7595-7607, ISSN 0021-9258, https://doi.org/10.1074/jbc.RA119.011630

    Jeffreys, L.N., Poddar, H., Golovanova, M. et al. Novel insights into P450 BM3 interactions with FDA-approved antifungal azole drugs. Sci Rep 9, 1577 (2019). https://doi.org/10.1038/s41598-018-37330-y