Projects per year
Personal profile
Research interests
I am a biophysicist with an interdisciplinary research group working at the interface of the biological and physical sciences. We use single molecule fluorescence spectroscopy and other techniques to measure changes in the conformation of protein drug targets with the ultimate aim of using our results to improve drug discovery. Our approach enables us to detect and quantify multiple populations in solution and to observe transient occupation of minority states directly. In particular, we specialise in measuring small distance changes and conformational changes in small proteins using dye quenching.
Protein kinases
Protein kinases regulate many cellular processes and are a major class of drug target, particularly in inflammation and oncology. Broadly speaking, x-ray structures show kinases in one of two major conformations which regulate kinase catalytic activity and are thought to influence the binding of kinase inhibitors. However, until recently, very little was known about whether individual molecules were locked in a single conformation or were in conformational equilibrium, whether this was driven by inhibitor binding, or what the timescale of any interconversion was.
By covalently attaching bright fluorescent dyes to known sites on the kinase surface, we directly measured the dynamic interconversion of a protein kinase between DFG-in-like active and DFG-out-like inactive conformations in solution for the first time. Among other discoveries, we have shown that the position of equilibrium can be changed by kinase ligands (eg physiological activators and drug-like inhibitors) and that ligand-bound kinase can also interconvert between conformations. This is a new way of thinking about kinase inhibition and there are many implications of our results, including how best to incorporate multiple protein structures into the process of structure-based drug design.
About Charlotte
I carried out my PhD research in protein folding at the MRC Centre for Protein Engineering (Cambridge, UK) in the lab of Alan Fersht. I then moved to work with Richard Bayliss on protein kinases at the Institute of Cancer Research, before a second postdoc in spectroscopy, microscopy and magnetoreception with Mark Wallace and Peter Hore at University of Oxford (where I also held a Fulford Junior Research Fellowship at Somerville College). In 2013 I won an Imperial College Research Fellowship to apply single molecule techniques to protein kinases and start my own research group at Imperial College London. I have worked in biophysics, structural biology, chemistry and biomedical departments before moving to Pharmacy & Pharmacology at University of Bath in 2018.
Willing to supervise doctoral students
I welcome motivated PhD students with a biological or physical science background who are interested in the physical measurement of biological molecules, drug discovery, mechanism of inhibition, image analysis or optics.
I am also very interested to hear from international students who have identified competitive sources of funding for which we might apply together. If you intend to apply for a scholarship please contact me well advance of your intended start date as there are University deadlines in addition to those of your funder.
Education/Academic qualification
Biophysics, Doctor of Philosophy, University of Cambridge
Award Date: 1 Apr 2008
Biochemistry, Bachelor of Arts, University of Cambridge
Award Date: 1 Jul 1996
External positions
Policy Advisory group member, Biochemical Society
1 May 2014 → 1 Nov 2019Projects
- 7 Finished
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Open, 3D printed fluorescence microscopy for cell imaging
Collins, J., Dodson, C., Stirling, J. & Bowman, R.
18/06/19 → 17/06/20
Project: Research-related funding
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The effect of clinical mutations and kinase ligands on conformation and dynamics of protein kinase drug targets
5/03/18 → 31/10/18
Project: Project at a former HEI
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Novel adjuvants for antibody-based cancer therapeutics: design, biological characterization and influence on membrane-protein structure.
Bubeck, D., Tate, E. & Dodson, C.
1/10/15 → 1/10/19
Project: Project at a former HEI
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Conformational selection in Aurora-A kinase: competition between activator- and inhibitor- promoted forms
1/10/15 → 1/04/17
Project: Project at a former HEI
Research output
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A simple, robust, universal assay for real-time enzyme monitoring by signalling changes in nucleoside phosphate anion concentration using a europium(III)-based anion receptor
Hewitt, S., Ali, R., Mailhot, R., Antonen, C., Dodson, C. & Butler, S., 28 May 2019, In: Chemical Science. 10, 20, p. 5373-5381 9 p.Research output: Contribution to journal › Article › peer-review
Open Access8 Citations (Scopus) -
Ligand discrimination between active and inactive activation loop conformations of Aurora-A kinase is unmodified by phosphorylation
Gilburt, J., Girvan, P., Blagg, J., Ying, L. & Dodson, C., 14 Apr 2019, In: Chemical Science. 10, 14, p. 4069-4076 8 p.Research output: Contribution to journal › Article › peer-review
Open Access1 Citation (Scopus)16 Downloads (Pure) -
Dynamic Equilibrium of the Aurora A Kinase Activation Loop Revealed by Single-Molecule Spectroscopy
Gilburt, J., Sarkar, H., Sheldrake, P., Blagg, J., Ying, L. & Dodson, C., 6 Sep 2017, In: Angewandte Chemie-International Edition. 56, 38, p. 11409-11414 6 p.Research output: Contribution to journal › Article › peer-review
Open Access18 Citations (Scopus) -
Dynamic equilibrium of Aurora-A kinase activation loop revealed by single molecule spectroscopy
Gilburt, J., Sarkar, H., Sheldrake, P., Blagg, J., Ying, L. & Dodson, C., 2017, EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS. Springer, Vol. 46. p. S315-S315 1 p.Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
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Kinetic Analysis Reveals the Identity of A beta-Metal Complex Responsible for the Initial Aggregation of A beta in the Synapse
Branch, T., Barahona, M., Dodson, C. & Ying, L., 16 Jun 2017, In: ACS Chemical Neuroscience. 8, 9, p. 1970-1979 10 p.Research output: Contribution to journal › Article › peer-review
Open Access13 Citations (Scopus)
Datasets
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Single molecule experimental data for intensity histograms in Gilburt et al, Angewandte 2017
Dodson, C. (Creator), Gilburt, J. (Creator) & Ying, L. (Creator), Zenodo, 11 Jul 2017
Dataset
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Single molecule experimental data for dwell time histogram in Gilburt et al, Angewandte Chemie 2017
Dodson, C. (Creator), Gilburt, J. (Creator) & Ying, L. (Creator), Zenodo, 11 Jul 2017
Dataset
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Single molecule experimental data for unphosphorylated Aurora-A measurements in Gilburt et al, Chemical Science 2019
Dodson, C. (Creator), Gilburt, J. (Creator) & Ying, L. (Creator), Zenodo, 7 Mar 2019
Dataset