Chemical Biology and Bioorganic Group Awards

Throughout her career, Zoë (FRSC and CChem) has been an exceptionally active member of the RSC including officer roles in the CBBG (2014-2024, elected Treasurer in 2018-2021) and the Nucleic Acid Group (2016 until present, elected Secretary in 2018) and the East Anglian Local Section (Chair 2013-2015). Zoë is an accreditor for Chemistry degrees (2016-Present) and a member of the RSC Chemistry Accreditation and Validation panel (Vice Chair 2021-2024, Chair from 2024). She led the creation of the “essential practical skills list”, now part of the new RSC accreditation criteria. Her teamwork and innovative approaches to education have also been recognised through both UCL and Pearson Team Awards.

Since establishing her independent research group in 2010, Zoë has built an international reputation on the study and characterisation of DNA i-motifs, four-stranded non-canonical DNA structures formed from sequences rich in cytosine. She applies a combination of synthetic, analytical and biophysical chemistry alongside cellular and molecular biology in collaborative efforts to understand the biological significance of these structures.

Zoë’s team showed for the first time that silver (I) cations can fold i-motif DNA at neutral pH (Chem Commun 2013, 49, 7696). They also showed that and copper (I) cations can fold DNA i-motifs whereas copper (II) cations fold into hairpins, allowing redox dependent modulation of DNA structure (Chem Commun 2015, 51, 14099, Nucleic Acids Res 2018, 46, 5886). The potential applications of this work in nanotechnology attracted media interest (e.g. ‘DNA shape changed by scientists to create tiny machines and computers - The Independent’). Zoë’s team also has determined features of i-motif sequences that can fold into i-motifs at neutral pH, and demonstrated multiple examples of sequences from the human genome that could potentially fold into i-motif under physiological conditions (Nucleic Acids Res 2017, 45, 2951).

Zoë’s collaborative work has revealed potential biological functions of i-motifs in human cells, including evidence that i-motif formation causes spontaneous deletions (Nucleic Acids Res. 2022, 50, 3445) and replication induced i-motif structures drive replication fork breakage (EMBO J. 2023 42, e114334). They have also identified chemical biology tools that can detect i-motifs in the presence of other DNA structures (J Am Chem Soc 2020, 142, 13856) and stabilise i-motifs in cells (J Am Chem Soc 2020, 142, 20600). Recent work includes the first crystal structure of an intramolecular i-motif and determination of a relationship between non-canonical structure formation and insulin gene expression (bioRxiv, 2023.06. 01.543149) and creation of a predictive i-motif tool “iMSeeker” (Nucleic Acids Res., 2024, 52, 2188; Nucleic Acids Res., 2024, DOI: 10.1093/nar/gkae315). Excitingly, both this new structural information and the predictive tool will enhance efforts to target i-motifs in drug discovery.

Throughout his career, Andrew has been an ardent supporter of the Royal Society of Chemistry (RSC). He was an active RSC CBBG committee member for six years and was elected Chair from 2017 to 2020, where his leadership resulted in significant growth of the committee fostering greater vibrancy, enthusiasm and engagement. He was also an invited Committee Member of the RSC Organic Division and in recognition of his valuable contributions, was elected to the RSC Organic Chemistry Community Council in 2023.

Beyond the RSC he was a member of the Society for Chemical Industry Young Chemists' Panel (YCP) (2010 to 2016), actively engaging in initiatives relevant to young chemists. Andrew has played a significant role in shaping the UK Chemical Biology research agenda through his extensive work on EPSRC panels and participation in community workshops. He has been a prolific meeting organiser including co-chairing four RSC CBBG Firbush conferences,  RSC CBBG Postgraduate meetings in Leicester and Glasgow as well as the Chemical Biology Meets Drug Discovery conference in 2018, and the Society of Chemical Industry YCP symposium on Epigenetics in 2017.

Andrew’s research in peptides and peptidomimetics for chemical biology is highly collaborative. This multidisciplinary area requires creativity, drive and a critical eye for detail. His work has multiple lines of investigation. This has included synthetic methods to generate nonproteinogenic amino acids (J. Am. Chem. Soc., 2009, 131, 7917, Org. Lett., 2019, 21, 3178).

He has developed histone deacetylase (HDAC) inhibitors resulting in significant insight into HDAC substrate recognition and HDAC recruitment to corepressor complexes including for example the mechanism of activation of class I HDAC complexes (Nat. Commun., 2016, 7, 11262; Cell Rep., 2020, 30, 2699).

Using this knowledge of HDAC biochemistry, his group developed novel HDAC substrate inhibitors using Fmoc amino acids incorporating zinc binding groups. (Org. Lett., 2019, 21, 3178; ACS Chem. Bio., 2022, 17, 2572). Andrew’s research has contributed extensively to the field of constrained peptides reporting one of the first examples of a stapled protein: a stapled TPX2 proteomimetic was demonstrated to have enhanced binding affinity for AuroraA kinase through molecular interactions not observed in the native protein-protein interaction (ACS Chem. Bio., 2016, 11, 3383).

He has also developed constrained μ-conotoxins that block human voltage gated sodium channels (Pep. Sci., 2021, 113, e24203) and most recently introduced bifunctional, Raman active diyne‐girder stapled α‐helical peptides (Eur. J. Chem., 2023, e202300855).

Excitingly, the Jamieson group has contributed broadly to collaborative research which unveiled and validated a new malarial drug target (e.g. Science, 2019, 365, eaau1682) and is pursuing translation opportunities this presents through his spin-out company Keltic Pharma Therapeutics, where Andrew acts as chief scientific officer.