Professor Chris Toseland
School of Medicine and Population Health
Professor of Cancer Biophysics
+44 114 215 9080
Full contact details
School of Medicine and Population Health
FU34, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX
- Profile
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For enquiries please contact - SMPH-West-Operational@sheffield.ac.uk
2019: Senior Lecturer/MRC Career Development Award Fellowship
School of Medicine & Population Health - University of Sheffield
2015 - 2019: MRC Career Development Award
Schools of Biosciences - University of Kent
April 2015: Leverhulme Early Career Research Fellow
Schools of Biosciences - University of Kent
2013 – 2015: Senior Post-Doc Researcher
Max-Planck Institute for Biochemistry, Munich, Germany
2010 – 2013: EMBO Long Term Fellow
LMU Munich, Munich, Germany
2009 – 2010: Post-Doctoral Research Associate
MRC National Institute for Medical Research, London, UK
2006 – 2009: PhD
MRC National Institute for Medical Research, London, UK
2002 – 2006: BSc Biochemistry
University of Wales - Aberystwyth
- Research interests
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The lab specialises in application of fluorescence and mechanical measurements from whole cells to single molecules. We are a multidisciplinary lab drawing upon core techniques in Cell Biology, Biochemistry, Biophysics, Mechanobiology, Super Resolution single molecule imaging and Genomics Gene expression, the transfer of the genetic code into cellular proteins is one of the most fundamental processes in living cells. This process is orchestrated by RNA polymerases, which are highly regulated to ensure correct expression.
A breakdown in this regulation leads to development disabilities and most notably cancer formation. Furthermore, changes in expression control embryonic development and stem cell differentiation.
Over the past decade it has become established that myosin motors are present in the nucleus and function in transcription, but what role they play in the organisation and transcription of genetic information is unclear.
For the first time we combine classical biochemical and single molecule assays to provide a quantitative high-resolution description of the activity of these nuclear myosins; providing a mechanistic insight into the activity of these proteins.
Please see External Lab HomePage for more information.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- High throughput mechanobiology : force modulation of ensemble biochemical and cell-based assays. Biophysical Journal, 120(4), 631-641.
- DNA damage alters nuclear mechanics through chromatin reorganization. Nucleic Acids Research, 49(1), 340-353. View this article in WRRO
- Nuclear myosins – roles for molecular transporters and anchors. Journal of Cell Science, 133(11).
- Competition between two high- and low-affinity protein-binding sites in myosin VI controls its cellular function.. Journal of Biological Chemistry, 295(2), 337-347.
- Research culture : a survey of new PIs in the UK. eLife, 2019(8). View this article in WRRO
- NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications, 8(-), ---.
- Atomic force microscopy micro-rheology reveals large structural inhomogeneities in single cell-nuclei. Scientific Reports, 7.
- Unconventional Myosins: How Regulation Meets Function. International Journal of Molecular Sciences, 21(1), 67-67.
All publications
Journal articles
- Actin from within – how nuclear myosins and actin regulate nuclear architecture and mechanics. Journal of Cell Science, 138(3). View this article in WRRO
- Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription. Nature Communications, 14. View this article in WRRO
- Myosin in chromosome organisation and gene expression. Biochemical Society Transactions, 51(3), 1023-1034. View this article in WRRO
- Binding partners regulate unfolding of myosin VI to activate the molecular motor. Biochemical Journal, 479(13), 1409-1428.
- Measuring Nuclear Mechanics with Atomic Force Microscopy, 171-181.
- Measuring Nuclear Organization of Proteins with STORM Imaging and Cluster Analysis, 293-309.
- Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nature Communications, 13(1).
- Magnetic tweezers in a microplate format. Journal of Visualized Experiments, 180. View this article in WRRO
- Regulation of nuclear mechanics and the impact on DNA damage. International Journal of Molecular Sciences, 22(6).
- The roles of nuclear myosin in the DNA damage response. The Journal of Biochemistry, 169(3), 265-271.
- High throughput mechanobiology : force modulation of ensemble biochemical and cell-based assays. Biophysical Journal, 120(4), 631-641.
- A targeted and tuneable DNA damage tool using CRISPR/Cas9. Biomolecules, 11(2).
- DNA damage alters nuclear mechanics through chromatin reorganization. Nucleic Acids Research, 49(1), 340-353. View this article in WRRO
- Nuclear myosins – roles for molecular transporters and anchors. Journal of Cell Science, 133(11).
- Competition between two high- and low-affinity protein-binding sites in myosin VI controls its cellular function.. Journal of Biological Chemistry, 295(2), 337-347.
- Research culture : a survey of new PIs in the UK. eLife, 2019(8). View this article in WRRO
- Binding partner regulation of Myosin VI: Loss of tumour-suppressor Dab2 leads to enhanced activity of nuclear myosin.
- Application of the SSB biosensor to study in vitro transcription. Biochemical and Biophysical Research Communications, 496(3), 820-825.
- NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications, 8(-), ---.
- Function of Nuclear Myosin Motors: A Biochemical and Single Molecule Characterization - MRC. Impact, 2017(10), 49-51.
- Atomic force microscopy micro-rheology reveals large structural inhomogeneities in single cell-nuclei. Scientific Reports, 7.
- A reagentless biosensor for mRNA: a new tool to study transcription.
- The mechanical response of talin. Nature Communications, 7.
- SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading mechanism in Bacillus subtilis. eLife, 4. View this article in WRRO
- Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination. Nucleic Acids Research, 43(7), 3841-3856. View this article in WRRO
- Molecular basis for SMC rod formation and its dissolution upon DNA binding. Molecular Cell, 57(2), 290-303. View this article in WRRO
- Rapid Reaction Kinetic Techniques, 49-65.
- Fluorescence and Labelling: How to Choose and What to Do, 1-24.
- Fluorescence to Study the ATPase Mechanism of Motor Proteins, 67-86.
- ATPase Mechanism of the 5′-3′ DNA Helicase, RecD2. Journal of Biological Chemistry, 288(35), 25183-25193.
- Fluorescent labeling and modification of proteins. Journal of Chemical Biology, 6(3), 85-95.
- Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD. Nucleic Acids Research, 41(9), 5010-5023.
- Cloning, Expression, and Characterization of a Novel Molecular Motor, Leishmania Myosin-XXI. Journal of Biological Chemistry, 287(33), 27556-27566.
- Parasite Motility: Mechanisms of a Novel Molecular Motor, Myosin XXI. Biophysical Journal, 102(3), 570a-570a.
- Fluorescent Nucleoside Triphosphates for Single-Molecule Enzymology, 161-174.
- A Single-Molecule Approach to Visualize the Unwinding Activity of DNA Helicases, 193-214.
- Visualizing helicases unwinding DNA at the single molecule level. Nucleic Acids Research, 38(13), 4448-4457.
- Fluorescence tools to measure helicase activity in real time. Methods, 51(3), 259-268.
- The ATPase Cycle of PcrA Helicase and Its Coupling to Translocation on DNA. Journal of Molecular Biology, 392(4), 1020-1032.
- Using databases and data mining in vaccinology. Expert Opinion on Drug Discovery, 2(1), 19-35.
- Alpha helical trans-membrane proteins: Enhanced prediction using a Bayesian approach.. Bioinformation, 1(6), 234-236.
- A predictor of membrane class: Discriminating alpha-helical and beta-barrel membrane proteins from non-membranous proteins.. Bioinformation, 1(6), 208-213.
- Beta barrel trans-membrane proteins: Enhanced prediction using a Bayesian approach.. Bioinformation, 1(6), 231-233.
- Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: In Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique.. ChemInform, 37(31).
- Benchmarking pKa prediction. BMC Biochemistry, 7(1).
- PPD v1.0--an integrated, web-accessible database of experimentally determined protein pKa values. Nucleic Acids Research, 34(90001), D199-D203.
- Toward Prediction of Class II Mouse Major Histocompatibility Complex Peptide Binding Affinity: in Silico Bioinformatic Evaluation Using Partial Least Squares, a Robust Multivariate Statistical Technique. Journal of Chemical Information and Modeling, 46(3), 1491-1502.
- . Immunome Research, 1(1), 4-4.
- Computational Chemistry, Informatics, and the Discovery of Vaccines. Current Computer Aided-Drug Design, 1(4), 377-395.
- Unconventional Myosins: How Regulation Meets Function. International Journal of Molecular Sciences, 21(1), 67-67.
- ATPase Cycle and DNA Unwinding Kinetics of RecG Helicase. PLoS ONE, 7(6), e38270-e38270.
- TATPred: a Bayesian method for the identification of twin arginine translocation pathway signal sequences. Bioinformation, 1(5), 184-187.
- LIPPRED: A web server for accurate prediction of lipoprotein signal sequences and cleavage sites. Bioinformation, 1(5), 176-179.
- DSD – An integrated, web-accessible database of Dehydrogenase Enzyme Stereospecificities. BMC Bioinformatics, 6(1).
Book chapters
- Helicases, Encyclopedia of Biophysics (pp. 950-958). Springer Berlin Heidelberg
- Erratum to: A Single-Molecule Approach to Visualize the Unwinding Activity of DNA Helicases, Methods in Molecular Biology (pp. E1-E1). Humana Press
- Empirical, AI, and QSAR Approaches to Peptide-MHC Binding Prediction, In Silico Immunology (pp. 139-175). Springer US
Conference proceedings
- Myosin VI and its Role in the DNA Damage Response. Biophysical Journal, Vol. 116(3) (pp 77a-77a)
- Nuclear Ndp52 - a Putative Transcription Regulator. Biophysical Journal, Vol. 116(3) (pp 210a-210a)
- Novel Tales About the Myosin VI Tail. Biophysical Journal, Vol. 116(3) (pp 178a-178a)
- Deciphering Load-Induced Anchoring by Myosin VI. Biophysical Journal, Vol. 116(3) (pp 260a-260a)
- Nuclear Myosin VI Stabilizes RNA Polymerase II in Transcription Factories. Biophysical Journal, Vol. 116(3) (pp 208a-209a)
- Nuclear Myosin VI Regulates Estrogen Receptor Driven Gene Expression. Biophysical Journal, Vol. 116(3) (pp 209a-209a)
- Activation of nuclear myosin VI leads to enhanced gene expression.. MOLECULAR BIOLOGY OF THE CELL, Vol. 27
- Dissecting the role of Myosin VI in the nucleus.. MOLECULAR BIOLOGY OF THE CELL, Vol. 27
- Myosin VI Comes Together - Structure and Motor Regulation by Binding Partners. Biophysical Journal, Vol. 102(3) (pp 569a-569a)
- Direct Observation of the Myosin Power Stroke and its Reversal. Biophysical Journal, Vol. 100(3) (pp 116a-116a)
- Single Molecule Fluorescence and Force Measurements on PcrA Helicase. Biophysical Journal, Vol. 100(3) (pp 72a-73a)
- PcrA Helicase ATPase Mechanism: RepD Modulation During Unwinding. Biophysical Journal, Vol. 96(3) (pp 415a-415a)
Preprints
- 3D environment promotes persistent changes in lamin B1 distribution, the biomechanical signature of the nucleus, and adaptative survival and migratory functions, Cold Spring Harbor Laboratory.
- Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription, Cold Spring Harbor Laboratory.
- A targeted and tuneable DNA damage tool using CRISPR/Cas9, Cold Spring Harbor Laboratory.
- DNA damage alters nuclear mechanics through chromatin reorganisation, Cold Spring Harbor Laboratory.
- Binding partners regulate unfolding of myosin VI to activate the molecular motor, Cold Spring Harbor Laboratory.
- High throughput mechanobiology: Force modulation of ensemble biochemical and cell-based assays, Cold Spring Harbor Laboratory.
- Nuclear myosin VI regulates the spatial organization of mammalian transcription initiation, Cold Spring Harbor Laboratory.
- Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements, Cold Spring Harbor Laboratory.
- High throughput mechanobiology : force modulation of ensemble biochemical and cell-based assays. Biophysical Journal, 120(4), 631-641.
- Research group
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- Dr Natalia Fili (Postdoctoral Research Associate)
- Rosemarie Gough (Postdoctoral Research Associate)
- Alexander Cook (Postdoctoral Research Associate)
- Alia dos Santos (PhD Student)
- Grants
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- Medical Research Council
- Cancer Research UK
- Science and Technology Facilities Council
- Royal Society
- Leverhulme Trust