Professor Chris Toseland

Clinical Medicine, School of Medicine and Population Health

Professor of Cancer Biophysics

c.toseland@sheffield.ac.uk
+44 114 215 9080

FU34, F Floor, The Medical School

Full contact details

Professor Chris Toseland
Clinical Medicine, School of Medicine and Population Health
FU34, F Floor
The Medical School
Beech Hill Road
Sheffield
S10 2RX

Profile

For enquiries please contact - ClinMed-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

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

Show: Featured publications All publications

Featured publications

Journal articles

Santos ÁD, Fili N, Pearson DS, Hari-Gupta Y & Toseland CP (2021) High throughput mechanobiology : force modulation of ensemble biochemical and cell-based assays. Biophysical Journal. View this article in WRRO
dos Santos A, Cook A, Gough R, Schilling M, Aleida Olszok N, Brown I, Wang L, Aaron J, Martin-Fernandez M, Rehfeldt F & Toseland C (2021) DNA damage alters nuclear mechanics through chromatin reorganization. Nucleic Acids Research, 49(1), 340-353. View this article in WRRO
Cook AW, Gough RE & Toseland CP (2020) Nuclear myosins – roles for molecular transporters and anchors. Journal of Cell Science, 133(11), jcs242420-jcs242420.
Fili N, Hari-Gupta Y, Aston B, dos Santos Á, Gough RE, Alamad B, Wang L, Martin-Fernandez ML & Toseland CP (2019) Competition between two high- and low-affinity protein-binding sites in myosin VI controls its cellular function.. Journal of Biological Chemistry. View this article in WRRO
Acton S, Bell A, Toseland C & Twelvetrees A (2019) Research culture : a survey of new PIs in the UK. eLife, 2019(8). View this article in WRRO
Fili N, Hari-Gupta Y, dos Santos Á, Cook A, Poland S, Ameer-Beg SM, Parsons M & Toseland CP (2017) NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications, 8. View this article in WRRO
Lherbette M, dos Santos Á, Hari-Gupta Y, Fili N, Toseland CP & Schaap IAT (2017) Atomic force microscopy micro-rheology reveals large structural inhomogeneities in single cell-nuclei. Scientific Reports, 7. View this article in WRRO
Fili N & Toseland CP () Unconventional Myosins: How Regulation Meets Function. International Journal of Molecular Sciences, 21(1), 67-67.

All publications

Journal articles

dos Santos Á, Fili N, Hari-Gupta Y, Gough RE, Wang L, Martin-Fernandez M, Aaron J, Wait E, Chew T-L & Toseland CP (2022) Binding partners regulate unfolding of myosin VI to activate the molecular motor. Biochemical Journal, 479(13), 1409-1428.
Hari-Gupta Y, Fili N, dos Santos Á, Cook AW, Gough RE, Reed HCW, Wang L, Aaron J, Venit T, Wait E , Grosse-Berkenbusch A et al (2022) Myosin VI regulates the spatial organisation of mammalian transcription initiation. Nature Communications, 13(1).
Dos Santos Á, Rehfeldt F & Toseland CP (2022) Measuring Nuclear Mechanics with Atomic Force Microscopy.. Methods Mol Biol, 2476, 171-181.
Dos Santos Á, Gough RE, Wang L & Toseland CP (2022) Measuring Nuclear Organization of Proteins with STORM Imaging and Cluster Analysis.. Methods Mol Biol, 2476, 293-309.
dos Santos Á & Toseland CP (2021) Regulation of nuclear mechanics and the impact on DNA damage. International Journal of Molecular Sciences, 22(6).
Emmanouilidis I, Fili N, Cook AW, Hari-Gupta Y, dos Santos Á, Wang L, Martin-Fernandez ML, Ellis PJI & Toseland CP (2021) A targeted and tuneable DNA damage tool using CRISPR/Cas9. Biomolecules, 11(2).
Santos ÁD, Fili N, Pearson DS, Hari-Gupta Y & Toseland CP (2021) High throughput mechanobiology : force modulation of ensemble biochemical and cell-based assays. Biophysical Journal. View this article in WRRO
dos Santos A, Cook A, Gough R, Schilling M, Aleida Olszok N, Brown I, Wang L, Aaron J, Martin-Fernandez M, Rehfeldt F & Toseland C (2021) DNA damage alters nuclear mechanics through chromatin reorganization. Nucleic Acids Research, 49(1), 340-353. View this article in WRRO
Cook AW & Toseland CP (2020) The roles of nuclear myosin in the DNA damage response. The Journal of Biochemistry.
Cook AW, Gough RE & Toseland CP (2020) Nuclear myosins – roles for molecular transporters and anchors. Journal of Cell Science, 133(11), jcs242420-jcs242420.
Fili N, Hari-Gupta Y, Aston B, dos Santos Á, Gough RE, Alamad B, Wang L, Martin-Fernandez ML & Toseland CP (2019) Competition between two high- and low-affinity protein-binding sites in myosin VI controls its cellular function.. Journal of Biological Chemistry. View this article in WRRO
Acton S, Bell A, Toseland C & Twelvetrees A (2019) Research culture : a survey of new PIs in the UK. eLife, 2019(8). View this article in WRRO
Cook A, Hari-Gupta Y & Toseland CP (2018) Application of the SSB biosensor to study in vitro transcription. Biochemical and Biophysical Research Communications, 496(3), 820-825. View this article in WRRO
Fili N, Hari-Gupta Y, dos Santos Á, Cook A, Poland S, Ameer-Beg SM, Parsons M & Toseland CP (2017) NDP52 activates nuclear myosin VI to enhance RNA polymerase II transcription. Nature Communications, 8. View this article in WRRO
Toseland C (2017) Function of Nuclear Myosin Motors: A Biochemical and Single Molecule Characterization - MRC. Impact, 2017(10), 49-51.
Lherbette M, dos Santos Á, Hari-Gupta Y, Fili N, Toseland CP & Schaap IAT (2017) Atomic force microscopy micro-rheology reveals large structural inhomogeneities in single cell-nuclei. Scientific Reports, 7. View this article in WRRO
Yao M, Goult BT, Klapholz B, Hu X, Toseland CP, Guo Y, Cong P, Sheetz MP & Yan J (2016) The mechanical response of talin. Nature Communications, 7. View this article in WRRO
Kang H-A, Shin H-C, Kalantzi A-S, Toseland CP, Kim H-M, Gruber S, Peraro MD & Oh B-H (2015) 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
Soh Y-M, Bürmann F, Shin H-C, Oda T, Jin KS, Toseland CP, Kim C, Lee H, Kim SJ, Kong M-S , Durand-Diebold M-L et al (2015) Molecular Basis for SMC Rod Formation and Its Dissolution upon DNA Binding. Molecular Cell, 57(2), 290-303. View this article in WRRO
Toseland CP & Geeves MA (2014) Rapid Reaction Kinetic Techniques, 49-65.
Fili N & Toseland CP (2014) Fluorescence and Labelling: How to Choose and What to Do, 1-24.
Toseland CP (2014) Fluorescence to Study the ATPase Mechanism of Motor Proteins, 67-86.
Toseland CP & Webb MR (2013) ATPase Mechanism of the 5′-3′ DNA Helicase, RecD2. Journal of Biological Chemistry, 288(35), 25183-25193.
Chisty LT, Toseland CP, Fili N, Mashanov GI, Dillingham MS, Molloy JE & Webb MR (2013) Monomeric PcrA helicase processively unwinds plasmid lengths of DNA in the presence of the initiator protein RepD. Nucleic Acids Research, 41(9), 5010-5023.
Toseland CP (2013) Fluorescent labeling and modification of proteins. Journal of Chemical Biology, 6(3), 85-95.
Batters C, Woodall KA, Toseland CP, Hundschell C & Veigel C (2012) Cloning, Expression, and Characterization of a Novel Molecular Motor,LeishmaniaMyosin-XXI. Journal of Biological Chemistry, 287(33), 27556-27566.
Batters C, Woodall K, Toseland C & Veigel C (2012) Parasite Motility: Mechanisms of a Novel Molecular Motor, Myosin XXI. Biophysical Journal, 102(3), 570a-570a.
Toseland CP & Webb MR (2011) Fluorescent Nucleoside Triphosphates for Single-Molecule Enzymology, 161-174.
Fili N, Toseland CP, Dillingham MS, Webb MR & Molloy JE (2011) A Single-Molecule Approach to Visualize the Unwinding Activity of DNA Helicases, 193-214.
Fili N, Mashanov GI, Toseland CP, Batters C, Wallace MI, Yeeles JTP, Dillingham MS, Webb MR & Molloy JE (2010) Visualizing helicases unwinding DNA at the single molecule level. Nucleic Acids Research, 38(13), 4448-4457.
Toseland CP & Webb MR (2010) Fluorescence tools to measure helicase activity in real time. Methods, 51(3), 259-268.
Toseland CP, Martinez-Senac MM, Slatter AF & Webb MR (2009) The ATPase Cycle of PcrA Helicase and Its Coupling to Translocation on DNA. Journal of Molecular Biology, 392(4), 1020-1032.
Davies MN, Guan P, Blythe MJ, Salomon J, Toseland CP, Hattotuwagama C, Walshe V, Doytchinova IA & Flower DR (2007) Using databases and data mining in vaccinology. Expert Opinion on Drug Discovery, 2(1), 19-35.
Taylor PD, Toseland CP, Attwood TK & Flower DR (2006) Alpha helical trans-membrane proteins: Enhanced prediction using a Bayesian approach.. Bioinformation, 1(6), 234-236.
Taylor PD, Toseland CP, Attwood TK & Flower DR (2006) A predictor of membrane class: Discriminating alpha-helical and beta-barrel membrane proteins from non-membranous proteins.. Bioinformation, 1(6), 208-213.
Taylor PD, Toseland CP, Attwood TK & Flower DR (2006) Beta barrel trans-membrane proteins: Enhanced prediction using a Bayesian approach.. Bioinformation, 1(6), 231-233.
Hattotuwagama CK, Toseland CP, Guan P, Taylor DJ, Hemsley SL, Doytchinova IA & Flower DR (2006) 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).
Davies MN, Toseland CP, Moss DS & Flower DR (2006) . BMC Biochemistry, 7(1), 18-18.
Hattotuwagama CK, Toseland CP, Guan P, Taylor DJ, Hemsley SL, Doytchinova IA & Flower DR (2006) 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.
Toseland CP (2006) PPD v1.0--an integrated, web-accessible database of experimentally determined protein pKa values. Nucleic Acids Research, 34(90001), D199-D203.
Toseland CP, McSparron HM & Flower DR (2005) . BMC Bioinformatics, 6(1), 283-283.
Toseland CP, Clayton DJ, McSparron H, Hemsley SL, Blythe MJ, Paine K, Doytchinova IA, Guan P, Hattotuwagama CK & Flower DR (2005) . Immunome Research, 1(1), 4-4.
Guan P, Davies M, Taylor D, Wan S, McSparron H, Hemsley S, Toseland C, Blythe M, Taylor P, Walshe V , Hattotuwagama C et al (2005) Computational Chemistry, Informatics, and the Discovery of Vaccines. Current Computer Aided-Drug Design, 1(4), 377-395.
Shahid-Fuente IW & Toseland CP () Myosin in chromosome organisation and gene expression. Biochemical Society Transactions.
Toseland C () Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription. Nature Communications.
Fili N & Toseland CP () Unconventional Myosins: How Regulation Meets Function. International Journal of Molecular Sciences, 21(1), 67-67.
Fili N, Hari-Gupta Y, Aston B, dos Santos Á, Gough RE, Alamad B, Wang L, Martin-Fernandez M & Toseland CP () Binding partner regulation of Myosin VI: Loss of tumour-suppressor Dab2 leads to enhanced activity of nuclear myosin.
Cook A, Hari-Gupta Y & Toseland CP () A reagentless biosensor for mRNA: a new tool to study transcription.
Wilhelm L, Bürmann F, Minnen A, Shin H-C, Toseland CP, Oh B-H & Gruber S () SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading mechanism in Bacillus subtilis. eLife, 4. View this article in WRRO
Toseland CP, Powell B & Webb MR () ATPase Cycle and DNA Unwinding Kinetics of RecG Helicase. PLoS ONE, 7(6), e38270-e38270.
Taylor PD, Toseland CP, Attwood TK & Flower DR () TATPred: a Bayesian method for the identification of twin arginine translocation pathway signal sequences. Bioinformation, 1(5), 184-187.
Taylor PD, Toseland CP, Attwood TK & Flower DR () LIPPRED: A web server for accurate prediction of lipoprotein signal sequences and cleavage sites. Bioinformation, 1(5), 176-179.
Toseland C & dos Santos A () Magnetic Tweezers in a Microplate Format. Journal of Visualized Experiments.

Chapters

Webb MR & Toseland CP (2013) Helicases, Encyclopedia of Biophysics (pp. 950-958). Springer Berlin Heidelberg
Fili N, Toseland CP, Dillingham MS, Webb MR & Molloy JE (2011) Erratum to: A Single-Molecule Approach to Visualize the Unwinding Activity of DNA Helicases, Single Molecule Enzymology (pp. E1-E1). Humana Press
Hattotuwagama CK, Guan P, Davies M, Taylor DJ, Walshe V, Hemsley SL, Toseland C, Doytchinova IA, Borrow P & Flower DR () Empirical, AI, and QSAR Approaches to Peptide-MHC Binding Prediction, In Silico Immunology (pp. 139-175). Springer US

Conference proceedings papers

Cook A, Hari Gupta Y, Venit T, Percipalle P & Toseland CP (2019) Myosin VI and its Role in the DNA Damage Response. Biophysical Journal, Vol. 116(3) (pp 77a-77a)
dos Santos A, Wang L & Toseland CP (2019) Nuclear Ndp52 - a Putative Transcription Regulator. Biophysical Journal, Vol. 116(3) (pp 210a-210a)
Fili N, Cook A, Hari Gupta Y & Toseland CP (2019) Novel Tales About the Myosin VI Tail. Biophysical Journal, Vol. 116(3) (pp 178a-178a)
Gough RE, Fili N, Hari Gupta Y & Toseland CP (2019) Deciphering Load-Induced Anchoring by Myosin VI. Biophysical Journal, Vol. 116(3) (pp 260a-260a)
Hari Gupta Y, Fili N, dos Santos A, Chew T-L, Aaron J, Wang L & Toseland CP (2019) Nuclear Myosin VI Stabilizes RNA Polymerase II in Transcription Factories. Biophysical Journal, Vol. 116(3) (pp 208a-209a)
Hari Gupta Y, Fili N, dos Santos A, Chew T-L, Aaron J, Wang L & Toseland CP (2019) Nuclear Myosin VI Regulates Estrogen Receptor Driven Gene Expression. Biophysical Journal, Vol. 116(3) (pp 209a-209a)
Fili N, dos Santos A, Hari-Gupta Y & Toseland CP (2016) Activation of nuclear myosin VI leads to enhanced gene expression.. MOLECULAR BIOLOGY OF THE CELL, Vol. 27
Fili N, Hari-Gupta Y & Toseland CP (2016) Dissecting the role of Myosin VI in the nucleus.. MOLECULAR BIOLOGY OF THE CELL, Vol. 27
Toseland CP, Ellrich H, Fili N, Batters C & Veigel C (2012) Myosin VI Comes Together - Structure and Motor Regulation by Binding Partners. Biophysical Journal, Vol. 102(3) (pp 569a-569a)
Veigel C, Batters C, Toseland CP & Sellers JR (2011) Direct Observation of the Myosin Power Stroke and its Reversal. Biophysical Journal, Vol. 100(3) (pp 116a-116a)
Toseland CP, Batters C & Veigel C (2011) Single Molecule Fluorescence and Force Measurements on PcrA Helicase. Biophysical Journal, Vol. 100(3) (pp 72a-73a)
Toseland CP & Webb MR (2009) PcrA Helicase ATPase Mechanism: RepD Modulation During Unwinding. Biophysical Journal, Vol. 96(3) (pp 415a-415a)

Preprints

González-Novo R, Zamora-Carreras H, de Lope-Planelles A, Menéndez HL, Roda-Navarro P, Monroy F, Wang L, Toseland CP & Muñoz JR (2023) 3D environment modulates persistent lamin distribution and the biomechanical signature of the nucleus, Cold Spring Harbor Laboratory.
dos Santos Á, Rollins DE, Hari-Gupta Y, Reed HCW, Du M, Ru SYZ, Pidlisna K, Stranger A, Lorgat F, Brown I , Howland K et al () Autophagy receptor NDP52 alters DNA conformation to modulate RNA Polymerase II transcription, Cold Spring Harbor Laboratory.
Emmanouilidis I, Fili N, Cook AW, Hari-Gupta Y, dos Santos Á, Wang L, Martin-Fernandez M, Ellis PJI & Toseland CP () A targeted and tuneable DNA damage tool using CRISPR/Cas9.
dos Santos Á, Cook AW, Gough RE, Schilling M, Olszok NA, Brown I, Wang L, Aaron J, Martin-Fernandez ML, Rehfeldt F & Toseland CP () DNA damage alters nuclear mechanics through chromatin reorganisation, Cold Spring Harbor Laboratory.
dos Santos Á, Fili N, Hari-Gupta Y, Gough RE, Wang L, Martin-Fernandez M, Aaron J, Wait E, Chew T-L & Toseland CP () Binding partners regulate unfolding of myosin VI to activate the molecular motor, Cold Spring Harbor Laboratory.
Santos ÁD, Fili N, Pearson DS, Hari-Gupta Y & Toseland CP () High throughput mechanobiology: Force modulation of ensemble biochemical and cell-based assays.
Hari-Gupta Y, Fili N, dos Santos Á, Cook AW, Gough RE, Reed HCW, Wang L, Aaron J, Venit T, Wait E , Grosse-Berkenbusch A et al () Nuclear myosin VI regulates the spatial organization of mammalian transcription initiation, Cold Spring Harbor Laboratory.
Große-Berkenbusch A, Hettich J, Kuhn T, Fili N, Cook AW, Hari-Gupta Y, Palmer A, Streit L, Ellis PJI, Toseland CP & Gebhardt JCM () Myosin VI moves on nuclear actin filaments and supports long-range chromatin rearrangements, Cold Spring Harbor Laboratory.

Research group

Dr Natalia Fili (Postdoctoral Research Associate)
Rosemarie Gough (Postdoctoral Research Associate)
Alexander Cook (Postdoctoral Research Associate)
Alia dos Santos (PhD Student)

Grants

Medical Research Council
Cancer Research UK
Science and Technology Facilities Council
Royal Society
Leverhulme Trust