Steven Bull
Principal Investigator
Prof Steven Bull is Head of School of Chemistry at the University of Leicester, where he also leads a research group. The group focuses on developing synthetic methodology to prepare functional molecules that exhibit interesting physical and biological properties.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Principal Investigator
Prof Steven Bull is Head of School of Chemistry at the University of Leicester, where he also leads a research group. The group focuses on developing synthetic methodology to prepare functional molecules that exhibit interesting physical and biological properties.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Principal Investigator
Prof Steven Bull is Head of School of Chemistry at the University of Leicester, where he also leads a research group. The group focuses on developing synthetic methodology to prepare functional molecules that exhibit interesting physical and biological properties.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Short Biography
Professor Steven Bull leads a multidisciplinary research group (The Bull Group) and has been serving as the Head of the School of Chemistry at the University of Leicester since 2023. The core of the research group is based on the development of new reactions, catalysts and protocols for the synthesis of structurally challenging molecules that exhibit specific biological functions.
Prof Bull earned his PhD in biocatalysis under supervision of Dr David Kelly at the University of Cardiff in 1990. This was followed by a postdoctoral studies at the University of Queensland (Australia) and at the University of Oxford. He then spent time working in drug discovery companies, before taking up a lectureship at St Catherine’s College, Oxford, in 1998. Before joining The University of Leicester, he was working at the University of Bath (lectureship in 2001 and full Professorship in Organic Chemistry and Drug Discovery in 2016).
AMBER postdoctoral fellowship subject (second call)
Defining how reactive metabolites regulate the protein cysteinome
The biology of reactive metabolites (RMs) such as aldehydes and reactive oxygen and sulfur species is undetermined at the molecular level. This is largely because RMs are difficult to work with (reactive, small, unstable, volatile) and can exhibit different effects at different concentrations. To fully define the biology of RMs, a holistic multidisciplinary approach is required that combines chemical biology tools with cellular methods.
Cysteine is redox-sensitive and is the most nucleophilic amino acid under physiological conditions. It is therefore the most likely amino acid on proteins to undergo reactions with RMs. There are a growing number of reported RM-cysteine reactiChristopher Switzerons on proteins, with many reported to induce functional changes. Many cysteine modifications are also reported to occur in disease and ageing. Understanding how RMs react with and affect the functions of cysteine-containing proteins is therefore of interest to basic science and biomedically focused research.
In this work, we will use bespoke RM-modulating chemical tools and imaging/detection methods to identify, characterise and phenotypically analyse RM reactions on cellular protein cysteines. Development of tool compounds will build on our previous expertise with aldehydes, reactive sulfur species and peroxynitrite, while the cellular work will use newly developed CRISPR methodology (recently published for lysines: DOI = 10.1016/j.molcel.2023.10.033) to screen for functionally relevant modifications. We will also monitor cysteine modifications (and selenocysteine modifications) in mouse models of ageing and oxidative stress. Ultimately the work will provide the first comprehensive overview of RM-mediated regulation of cysteines that should lead to new treatments against human disease.
Project leadership team: Richard Hopkinson (University of Leicester), Steven Bull (University of Leicester), Christopher Switzer (University of Leicester)
Location: Leicester, UK
Organisation: University of Leicester, School of Chemistry
Links
AMBER call in EURAXESS main call (starting point for application)
Steven Bull's Profile on the University of Leicester website