Research Areas

Structure-Guided Inhibitor Design on RNA Modifying Proteins

We determine structures of protein-inhibitor complexes using X-ray crystallography to guide development of anti-cancer and anti-viral compounds. We focus primarily on DNA or RNA binding proteins, which play important roles in gene regulation and disease development.

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• Shifali Shishodia, Marina Demetriades, Dong Zhang, Nok Yin Tam, Pratheesh Maheswaran, Caitlin Clunie-O’Connor, Anthony Tumber, Ivanhoe K. H. Leung, Yi Min Ng, Thomas M. Leissing, Afaf H. El-Sagheer, Eidarus Salah, Tom Brown, Wei Shen Aik*, Michael A. McDonough*, and Christopher J. Schofield*. Structure-Based Design of Selective Fat Mass and Obesity Associated Protein (FTO) Inhibitors. Journal of Medicinal Chemistry 2021 64 (22), 16609-16625. https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.1c01204

Structural Biology of Protein-RNA Complexes

We are intrigued by how proteins regulate genes on the RNA transcript level, especially through post-transcriptional modifications. In this area of research, we investigate how molecular machines that modify RNA using structural biology techniques such as protein crystallography and cryo-electron microscopy. We are also interested in investigating how viruses modify RNA.

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• Simranjeet Kaur, Nok Yin Tam, Michael A McDonough*, Christopher J Schofield*, Wei Shen Aik*, Mechanisms of substrate recognition and N6-methyladenosine demethylation revealed by crystal structures of ALKBH5–RNA complexes, Nucleic Acids Research, 2022;, gkac195, https://doi.org/10.1093/nar/gkac195

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Macromolecular Assembly Engineering

We are also exploring the use of macromolecules as drug delivery agents. We take advantage of structural biology and biophysical techniques to guide our design.