Christopher Switzer
Principal Investigator
Dr Christopher Switzer is Lecturer at the Department of Molecular and Cell Biology at the University of Leicester. His research interests include tumour microenvironment, nitric oxide and S-nitrosylation, immune suppression and epigenetic regulation.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Principal Investigator
Dr Christopher Switzer is Lecturer at the Department of Molecular and Cell Biology at the University of Leicester. His research interests include tumour microenvironment, nitric oxide and S-nitrosylation, immune suppression and epigenetic regulation.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Principal Investigator
Dr Christopher Switzer is Lecturer at the Department of Molecular and Cell Biology at the University of Leicester. His research interests include tumour microenvironment, nitric oxide and S-nitrosylation, immune suppression and epigenetic regulation.
Project in second call:
Defining how reactive metabolites regulate the protein cysteinome
Short Biography
Dr Christopher Switzer joined the University of Leicester as a lecturer at the Department of Molecular and Cell Biology in 2023.
He earned his PhD in Chemistry at the University of California (UCLA) in 2004, on the topic of “synthesis, Isolation and Characterization of Oxonitrate(1-) Salts”. This was followed by research positions at UCLA, The National Institutes of Health (US), King’s College in London, and Queen Mary University of London.
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 reactions 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, The Department of Molecular and Cell Biology
Links
AMBER call in EURAXESS main call (starting point for application)
Christopher Switzer's Profile on the University of Leicester website
The Department of Molecular and Cell Biology, University of Leicester