Staff profile

Liz Morris completed her undergraduate studies in Natural Sciences (Chemistry) at Cambridge in 2008, undertaking a Part III (final year) research project in the lab of Sophie Jackson on the folding mechanism of a trefoil-knotted protein. Liz was supervised by Prof Mark Searle in the Chemistry Department of the University of Nottingham for a PhD (2008-2012) on the structure and RNA-binding of a novel post-transcriptional regulator from Pseudomonas aeruginosa. In April 2012, Liz moved to the University of Edinburgh to the lab of Julia Richardson in the Institute of Structural and Molecular Biology to study the mechanism of a eukaryotic DNA transposon, Mos1. Here, Liz crystallised and solved the X-ray structure of a challenging protein-DNA complex to reveal the base-flipping mechanism by which the transposase searches chromosomal DNA for an integration site. Continuing her interest in enzyme mechanisms and protein-nucleotide interactions, Liz carried out a second post-doc (2015-2021), this time at The Francis Crick Institute, London in the HIV structural biology lab of Ian Taylor. X-ray crystal structures of inhibitors bound to the human anti-viral and anti-cancer enzyme SAMHD1 revealed the catalytic mechanism by which this enzyme hydrolyses nucleotides, but also several widely used nucleotide analogue anti-viral and anti-cancer agents, thereby modulating their efficacy. In March 2022, Liz was appointed to the Department of Biosciences at Durham University as an Assistant Professor in Biochemistry, where she is using structural biology and biophysical techniques to study how human pathogenic viruses replicate.

Research Interests

• Structural biology
• Biophysics
• Biochemistry
• Virology

Recent epidemics and pandemics demonstrate a gap in our understanding of viral infection. Viral genomes (RNA or DNA) encode the proteins that viruses use to infect and replicate in a cell. In addition, due to the limited size of viral genomes, viruses hijack their host cell’s machinery to support replication. Viruses have evolved different mechanisms for entering and exploiting their host cell. In my lab, we are studying enzyme mechanisms and protein-protein and protein-nucleotide interactions involved in virus replication, with the aim of identifying new druggable interfaces and screening them with small molecule libraries.

 

Journal Article

• Acton, O. J., Sheppard, D., Kunzelmann, S., Caswell, S. J., Nans, A., Burgess, A. J. O., Kelly, G., Morris, E. R., Rosenthal, P. B., & Taylor, I. A. (2024). Platform-directed allostery and quaternary structure dynamics of SAMHD1 catalysis. Nature Communications, 15(1), Article 3775. https://doi.org/10.1038/s41467-024-48237-w
• Tsai, M.-H. C., Caswell, S. J., Morris, E. R., Mann, M. C., Pennell, S., Kelly, G., Groom, H. C., Taylor, I. A., & Bishop, K. N. (2023). Attenuation of reverse transcriptase facilitates SAMHD1 restriction of HIV-1 in cycling cells. Retrovirology, 20(1), Article 5. https://doi.org/10.1186/s12977-023-00620-z
• Morris, E., Kunzelmann, S., Caswell, S., Purkiss, A., Kelly, G., & Taylor, I. (2021). Probing the Catalytic Mechanism and Inhibition of SAMHD1 Using the Differential Properties of Rp-and Sp-dNTPαS Diastereomers. Biochemistry, 60(21), 1682-1698. https://doi.org/10.1021/acs.biochem.0c00944
• Morris, E., Caswell, S., Kunzelmann, S., Arnold, L., Purkiss, A., Kelly, G., & Taylor, I. (2020). Crystal structures of SAMHD1 inhibitor complexes reveal the mechanism of water-mediated dNTP hydrolysis. Nature Communications, 11(1), https://doi.org/10.1038/s41467-020-16983-2
• Monit, C., Morris, E., Ruis, C., Szafran, B., Thiltgen, G., Tsai, M.-H., Mitchison, N., Bishop, K., Stoye, J., Taylor, I., Fassati, A., & Goldstein, R. (2019). Positive selection in dNTPase SAMHD1 throughout mammalian evolution. Proceedings of the National Academy of Sciences, 116(37), 18647-18654. https://doi.org/10.1073/pnas.1908755116
• Morris, E., & Taylor, I. (2019). The missing link: Allostery and catalysis in the anti-viral protein SAMHD1. Biochemical Society Transactions, 47(4), 1013-1027. https://doi.org/10.1042/bst20180348
• Flett, F., Ruksenaite, E., Armstrong, L., Bharati, S., Carloni, R., Morris, E., Mackay, C., Interthal, H., & Richardson, J. (2018). Structural basis for DNA 3′-end processing by human tyrosyl-DNA phosphodiesterase 1. Nature Communications, 9(1), https://doi.org/10.1038/s41467-017-02530-z
• Morris, E., Grey, H., McKenzie, G., Jones, A., & Richardson, J. (2016). A bend, flip and trap mechanism for transposon integration. eLife, 5(MAY2016), https://doi.org/10.7554/elife.15537
• Trubitsyna, M., Morris, E., Finnegan, D., & Richardson, J. (2014). Biochemical characterization and comparison of two closely related active mariner transposases. Biochemistry, 53(4), 682-689. https://doi.org/10.1021/bi401193w
• Wolkowicz, U., Morris, E., Robson, M., Trubitsyna, M., & Richardson, J. (2014). Structural basis of Mos1 transposase inhibition by the anti-retroviral drug raltegravir. ACS Chemical Biology, 9(3), 743-751. https://doi.org/10.1021/cb400791u
• Kulkarni, P., Jia, T., Kuehne, S., Kerkering, T., Morris, E., Searle, M., Heeb, S., Rao, J., & Kulkarni, R. (2014). A sequence-based approach for prediction of CsrA/RsmA targets in bacteria with experimental validation in Pseudomonas aeruginosa. Nucleic Acids Research, 42(11), 6811-6825. https://doi.org/10.1093/nar/gku309
• Morris, E., Hall, G., Li, C., Heeb, S., Kulkarni, R., Lovelock, L., Silistre, H., Messina, M., Cámara, M., Emsley, J., Williams, P., & Searle, M. (2013). Structural rearrangement in an RsmA/CsrA Ortholog of pseudomonas aeruginosa creates a dimeric RNA-binding protein, RsmN. Structure, 21(9), 1659-1671. https://doi.org/10.1016/j.str.2013.07.007
• Morris, E., & Searle, M. (2012). Overview of protein folding mechanisms: Experimental and theoretical approaches to probing energy landscapes. https://doi.org/10.1002/0471140864.ps2802s68
• Mallam, A., Morris, E., & Jackson, S. (2008). Exploring knotting mechanisms in protein folding. Proceedings of the National Academy of Sciences, 105(48), 18740-18745. https://doi.org/10.1073/pnas.0806697105