Prof Michelle Peckham
BA, York; PhD 1984, London.
Professor of Cell Biology
School of Molecular and Cellular Biology
Background: Our research group works broadly on the cytoskeleton and cytoskeletal molecular motors, myosins and kinesins, to understand the structure, function and how the activity of these proteins are regulated in cells, as well as how these proteins are implicated in and contribute to disease processes. The involvement of many muscle myosins in heart and skeletal muscle disease has led to us developing an interest in muscle development, and the contribution of satellite cells (muscle stem cells) to muscle formation. We use a wide range of tools and approaches to address key questions about molecular motors, that include a wide range of cell and molecular biology techniques, protein expression and purification, as well as light microscopy, electron microscopy, X-ray crystallography, NMR, AFM and other biophysical approaches, ofter through collaborating with other research groups at Leeds. We are also developing 'super-resolution' imaging approaches, including PALM/STORM, and iSIM.
Contact: Astbury 8.106 | +44(0) 113 34 34348 |
You can read more about Prof Peckham's interests here:
Myosins, motors, and muscle in health and disease
We are funded by BBSRC to investigate the structure and function of stable single alpha helical domains. These domains are found in myosins and a wide range of other proteins, and appear to act as 'constant force springs' (Wolny et al., J. Biol. Chem. 2014). We think that they can unfold at low forces and then refold, which means that a force applied to the protein will unfold the SAH domain, but allow domains in the protein either side of the SAH domain to remain attached to their binding partners.
We are funded by MRC to investigate how mutations in slow (beta-cardiac) myosin heavy chain in the coiled-coil tail cause skeletal muscle diseases such as Laing's distal myopathy. We are using a combination of protein structure determination and cell biology to investigate how mutations affect the structure of the coiled-coil to understand this process.
We are funded by MRC to build and develop super-resolution imaging technologies such as PALM/STORM and iSIM. These technologies break or overcome the resolution limit of a normal wide-field microscope, allowing us to see a more detailed view of cellular structures.
We are funded by the Wellcome Trust to investigate how the activity of non-muscle myosin isoforms are regulated in cells. Non-muscle myosins are self-regulating. For example, the tail of the myosin interacts with the motor domain to prevent the motor from interacting with its actin track in myosin 5, 7 and 2, and probably many other myosins. (e.g. Baboolal et al., PNAS 2009). What is the nature of this interaction? How is this overcome so that the motor can be switched on?
PhD students in the lab are also studying aspects of these problems, including modelling of myosin 7 (EPSRC funded, with Sarah Harris, Oliver Harlen and Daniel Read in MAPS), using super-resolution microscopy, crystallography and electron microscopy to study the Z-disc (BBSRC DTP funded, with Neil Ranson and Thomas Edwards in FBS), the study of MEGF10 in satellite cells (with Colin Johnson at LIBACS), the study of myosin 5 (with Peter Knight and Jim Sellers (NIH), the contribution of myosins to cell migration and metastasis (CRUK funded, with Claire Well, KCL), and super-resolution imaging of virus complexes in cells (with Mark Harris, Wellcome Trust funded).
Faculty Research and Innovation
Undergraduate project topics:
- Structure and functions of myosins, roles of proteins in the Z-disc in muscle
Postgraduate studentship areas:
- The structure and function of myosins and other molecular motors in muscle and non-muscle cells. Their roles in diseases. Super-resolution microscopy to obtain high resolution images of the cytoskeleton in muscle and non-muscle cells.
- Two specific projects are:
- How big is your brain?
- Brain size (and thus IQ) has been linked to an unusual protein called ASPM (abnormal spindle-like, microcephaly-associated), which contains 81 ‘IQ’ motifs. IQ motifs are known to bind calmodulin. This protein is important in mitosis and meiosis, and it is upregulated in many different cancers. However, we do not understand how this protein works. This project will use a combination of live cell imaging (including super-resolution imaging) and structural biology techniques to gain new insight into the function of this protein.
- (jointly supervised with Jacqueline Bond in Faculty of Medicine and Health)
- How is kinesin activity regulated? (with Joe Cockburn in the School of Molecular and Cellular Biology)
- Kinesins are important molecular motors that traffic proteins and organelles in cells. Mutations in kinesin-3 family members cause diseases such as amyotrophic lateral sclerosis. This project will find out how these motors are connected to and activated by their cargo. It will use a wide range of cutting edge techniques from atomic resolution X-ray crystallography on motor-cargo complexes, to super-resolution imaging in live and fixed cells (iSIM and PALM/STORM), and will provide an excellent training in these cutting edge techniques.
- Background: The kinesin-3 family motors constitute one of the largest families of kinesin motors, and are key players in the microtubule transport of cargos in a wide variety of processes such as vesicle transport, mitosis and development. We recently demonstrated that they are the most processive of all molecular motors described to date, and that these ‘marathon runners’ of the cellular world are regulated by a monomer-to-dimer transition induced by cargo binding.
- The compact, monomeric form of kinesin-3 is stabilized by intramolecular interactions between the neck coil (NC) and the first coiled coil (CC1) segments immediately downstream from the motor domain. Cargo binding perturbs these interactions, resulting in a super-processive dimer. The molecular mechanisms of kinesn-3 recruitment by cargoes and the ensuing monomer-to-dimer transition, and how this activates super-processive motility, however, are not understood.
- Objective: To obtain a detailed, molecular understanding of cargo binding to kinesin-3 tail regions and how this regulates kinesin-3 motility in vitro and in vivo.
External Examiner (taught course): University College Dublin
Faculty Research & Innovation Committee
FBS Exective Committee
FBS Faculty Board
FBS Graduate School Committee (Chair)
FBS Promotions panel
FBS Student Recruitment Committee
BIOL2211 - Human Diseases
BIOC1301 - Intro Inte Biochem Mol Process
BIOC2201/SPSC2201 - Exercise Biochemistry
BIOC2301/MICR2120 - Integrated Biochemistry/Medical Bacteriology
BIOC3111/12/BIOL3112 d - ATU 08 - Cell motility & trafficking
BIOC3160 - Lab/Lit/Comp Research Project
BIOL1212 - Tissues, Organs & Processes
BIOL2211 - Human Diseases
BIOL5212M/5321M - Bioimaging
BIOL5292M - Bioscience MSc Research Proj
BIOL5294M - MSc Bioscience Res Project Pro
BMSC1103 - Basic Laboratory and Scientific Skills
BMSC3101 - Inherited Disorders
DSUR1127 - Health and Health promotion
SPSC2201 - Exercise Biochemistry
Chair of Graduate School Committee
- The Astbury Centre for Structural Molecular Biology
- The Multidisciplinary Cardiovascular Research Centre (MCRC)
Group Leader Prof Michelle Peckham (Professor of Cell Biology)
Myosins, motors, and muscle in health and disease
Dr Matthew Batchelor (Research Fellow)
Dr Sally Boxall (Research Facility Manager)
Dr Alistair Curd (Research Fellow)
Dr Marta Kurzawa (Research Technician)
Dr Francine Parker (Research Fellow)
Dr Kathryn White (Research Fellow)
Dr Marcin Wolny (Research Fellow)
Baboolal TG; Sakamoto T; Forgacs E; White HD; Jackson SM; Takagi Y; Farrow RE; Molloy JE; Knight PJ; Sellers JR; Peckham M The SAH domain extends the functional length of the myosin lever P NATL ACAD SCI USA 106 22193-22198, 2009
Yang Y; Baboolal TG; Siththanandan V; Chen M; Walker ML; Knight PJ; Peckham M; Sellers JR A FERM domain autoregulates Drosophila myosin 7a activity P NATL ACAD SCI USA 106 4189-4194, 2009
Dunn S; Morrison EE; Liverpool TB; Molina-Paris C; Cross RA; Alonso MC; Peckham M Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules in live cells J CELL SCI 121 1085-1095, 2008
Soppina V; Norris SR; Dizaji AS; Kortus M; Veatch S; Peckham M; Verhey KJ Dimerization of mammalian kinesin-3 motors results in superprocessive motion Proceedings of the National Academy of Sciences of the United States of America 111 5562-5567, 2014
Wolny M; Batchelor M; Parker F; Baboolal T; Mashanov G; Molloy J; Paci E; Dougan L; Knight PJ; Peckham M Unravelling the Properties of Single alpha-Helical Domains in Myosin and other Proteins, 2014
Wolny M; Colegrave M; Colman L; White E; Knight P; Peckham M Cardiomyopathy mutations in the tail of beta cardiac myosin modify the coiled-coil structure and affect integration into thick filaments in muscle sarcomeres in adult cardiomyocytes. Journal of Biological Chemistry 288 31952-31962, 2013
Riches K; Franklin L; Maqbool A; Peckham M; Adams M; Bond J; Warburton P; Feric NT; Koschinsky ML; O'Regan DJ; Ball SG; Turner NA; Porter KE Apolipoprotein(a) acts as a chemorepellent to human vascular smooth muscle cells via integrin alpha(v)beta(3) and RhoA/ROCK-mediated mechanisms INTERNATIONAL JOURNAL OF BIOCHEMISTRY&CELL BIOLOGY 45 1776-1783, 2013
Stones R; Benoist D; Peckham M; White E Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension. J Mol Cell Cardiol 56 91-96, 2013
Sevdali M; Kumar V; Peckham M; Sparrow J Human congenital myopathy actin mutants cause myopathy and alter Z-disc structure in Drosophila flight muscle. Neuromuscular disorders : NMD 23 243-255, 2013
Mashanov GI; Nenasheva TA; Peckham M; Molloy JE Myosin-6 Mobility at the Plasma Membrane of Cultured Mammalian Cells, 2012
Yoon JR; Whipple RA; Balzer EM; Cho EH; Matrone MA; Peckham M; Martin SS Local anesthetics inhibit kinesin motility and microtentacle protrusions in human epithelial and breast tumor cells BREAST CANCER RES TR 129 691-701, 2011
Peckham M Coiled coils and SAH domains in cytoskeletal molecular motors BIOCHEM SOC T 39 1142-1148, 2011
Allsop G; Peckham M Cytoskeleton and Cell Motility In Comprehensive Biotechnology , 2011
Peckham M Histology at a Glance, 2011
Thompson O; Moore CJ; Hussaina SA; Kleino I; Peckham M; Hohenester E; Ayscough KR; Saksela K; Winder SJ Modulation of cell spreading and cell-substrate adhesion dynamics by dystroglycan J CELL SCI 123 118-127, 2010
Peckham M Journal club. A cell biologist ponders an outstanding mystery in muscle formation. Nature 458 1081-1081, 2009
Peckham M; Knight PJ When a predicted coiled coil is really a single alpha-helix, in myosins and other proteins SOFT MATTER 5 2493-2503, 2009
Ridley A; Peckham M; Clark P Introduction Journal of Microscopy 231 440-440, 2008
Peltzer J; Colman L; Cebrian J; Musa H; Peckham M; Keller A Novel murine clonal cell lines either express slow or mixed (fast and slow) muscle markers following differentiation in vitro DEV DYNAM 237 1412-1423, 2008
Domazetovska A; Ilkovski B; Kumar V; Valova VA; Vandebrouck A; Hutchinson DO; Robinson PJ; Cooper ST; Sparrow JC; Peckham M; North KN Intranuclear rod myopathy: Molecular pathogenesis and mechanisms of weakness ANN NEUROL 62 597-608, 2007
Mashanov GI; Nenasheva TA; Peckham M; Molloy JE Cell biochemistry studied by single-molecule imaging BIOCHEM SOC T 34 983-988, 2006
Musa H; Meek S; Gautel M; Peddie D; Smith AJH; Peckham M Targeted homozygous deletion of M-band titin in cardiomyocytes prevents sarcomere formation J CELL SCI 119 4322-4331, 2006
Swailes NT; Colegrave M; Knight PJ; Peckham M Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse J CELL SCI 119 3561-3570, 2006
Peckham M Research Highlights: Journal Club Nature pp.895-, 2006
Murphy JE; Tacon D; Tedbury PR; Hadden JM; Knowling S; Sawamura T; Peckham M; Phillips SEV; Walker JH; Ponnambalam S LOX-1 scavenger receptor mediates calcium-dependent recognition of phosphatidylserine and apoptotic cells BIOCHEM J 393 107-115, 2006
Knight PJ; Thirumurugan K; Xu YH; Wang F; Kalverda AP; Stafford WF; Sellers JR; Peckham M The predicted coiled-coil domain of myosin 10 forms a novel elongated domain that lengthens the head J BIOL CHEM 280 34702-34708, 2005
Swailes NT; Knight PJ; Peckham M Actin filament organization in aligned prefusion myoblasts J ANAT 205 381-391, 2004
Tacon D; Knight PJ; Peckham M Imaging myosin 10 in cells BIOCHEMICAL SOCIETY TRANSACTIONS 32 689-693, 2004
Mashanov GI; Tacon D; Peckham M; Molloy JE The spatial and temporal dynamics of pleckstrin homology domain binding at the plasma membrane measured by Imaging single molecules in live mouse myoblasts J BIOL CHEM 279 15274-15280, 2004
Ridley A; Clark P; Peckham M Cell Motility, from molecules to organisms, 2004
Miller G; Musa H; Gautel M; Peckham M A targeted deletion of the C-terminal end of titin, including the titin kinase domain, impairs myofibrillogenesis J CELL SCI 116 4811-4819, 2003
Miller G; Maycock J; White E; Peckham M; Calaghan S Heterologous expression of wild-type and mutant beta-cardiac myosin changes the contractile kinetics of cultured mouse myotubes. J Physiol 548 167-174, 2003
Musa H; Orton C; Morrison EE; Peckham M Microtubule assembly in cultured myoblasts and myotubes following nocodazole induced microtubule depolymerisation. J Muscle Res Cell Motil 24 301-308, 2003
Mashanov GI; Tacon DS; Knight AE; Peckham M; Molloy JE Visualizing single molecules inside living cells using total internal reflection fluorescence microscopy. Methods: A Companion to Methods in Enzymology 29 142-152, 2003
Clark P; Dunn GA; Knibbs A; Peckham M Alignment of myoblasts on ultrafine gratings inhibits fusion in vitro INT J BIOCHEM CELL B 34 816-825, 2002
Natali AJ; Wilson LA; Peckham M; Turner DL; Harrison SM; White E Different regional effects of voluntary exercise on the mechanical and electrical properties of rat ventricular myocytes Journal of Physiology 541 863-875, 2002
Dobrzynski H; Musa H; Claydon TW; Coppen SR; Dupont E; Severs NJ; Peckham M; Billeter-Clark R; Boyett MR Different distribution and cellular localisation of connexin43 and a-myosin heavy chain mRNA in the sinoatrial node. Pflugers Archiv: European Journal of Physiology 443 pp.208-, 2002
Peckham M; Miller G; Wells C; Zicha D; Dunn GA Specific changes to the mechanism of cell locomotion induced by overexpression of beta-actin J CELL SCI 114 1367-1377, 2001
Miller G; Colegrave M; Peckham M N232S, G741R and D778G beta-cardiac myosin mutants, implicated in familial hypertrophic cardiomyopathy, do not disrupt myofibrillar organisation in cultured myotubes FEBS LETT 486 325-327, 2000
Maggs AM; Taylor-Harris P; Peckham M; Hughes SM Evidence for differential post-translational modifications of slow myosin heavy chain during murine skeletal muscle development. J Muscle Res Cell Motil 21 101-113, 2000
Harris JM; Morgan JE; Rosenblatt JD; Rosenblatt D; Peckham M; Partridge T Forced MyHCIIB expression following targeted genetic manipulation of conditionally immortalized muscle precursor cells Experimental Cell Research 253 523-532, 1999
Peckham M; Wells C; Taylor-Harris P; Coles D; Zicha D; Dunn GA Using molecular genetics as a tool in understanding crawling cell locomotion in myoblasts Biochemical Society Symposium 65 281-299, 1999
Wells C; Coles D; Entwistle A; Peckham M Myogenic cells express multiple myosin isoforms J MUSCLE RES CELL M 18 501-515, 1997
Clark P; Coles D; Peckham M Preferential adhesion to and survival on patterned laminin organizes myogenesis in vitro EXP CELL RES 230 275-283, 1997
Peckham M; Young P; Gautel M Constitutive and variable regions of Z-disk titin/connectin in myofibril formation: A dominant-negative screen Cell Structure and Function 22 95-101, 1997
PECKHAM M; FERENCZI MA; IRVING M A BIREFRINGENCE STUDY OF CHANGES IN MYOSIN ORIENTATION DURING RELAXATION OF SKINNED MUSCLE-FIBERS INDUCED BY PHOTOLYTIC ATP RELEASE BIOPHYS J 67 1141-1148, 1994
MORGAN JE; BEAUCHAMP JR; PAGEL CN; PECKHAM M; ATALIOTIS P; JAT PS; NOBLE MD; FARMER K; PARTRIDGE TA MYOGENIC CELL-LINES DERIVED FROM TRANSGENIC MICE CARRYING A THERMOLABILE T-ANTIGEN - A MODEL SYSTEM FOR THE DERIVATION OF TISSUE-SPECIFIC AND MUTATION-SPECIFIC CELL-LINES DEV BIOL 162 486-498, 1994
PECKHAM M; CRIPPS R; WHITE D; BULLARD B MECHANICS AND PROTEIN-CONTENT OF INSECT FLIGHT MUSCLES J EXP BIOL 168 57-76, 1992
PECKHAM M; WHITE DCS MECHANICAL-PROPERTIES OF DEMEMBRANATED FLIGHT-MUSCLE FIBERS FROM A DRAGONFLY J EXP BIOL 159 135-147, 1991
Sparrow J; Drummond D; Peckham M; Hennessey E; White D Protein engineering and the study of muscle contraction in Drosophila flight muscles. J Cell Sci Suppl 14 73-78, 1991
DRUMMOND DR; PECKHAM M; SPARROW JC; WHITE DCS ALTERATION IN CROSSBRIDGE KINETICS CAUSED BY MUTATIONS IN ACTIN NATURE 348 440-442, 1990
Peckham M; Molloy JE; Sparrow JC; White DC Physiological properties of the dorsal longitudinal flight muscle and the tergal depressor of the trochanter muscle of Drosophila melanogaster. J Muscle Res Cell Motil 11 203-215, 1990
PECKHAM M; IRVING M MYOSIN CROSSBRIDGE ORIENTATION IN DEMEMBRANATED MUSCLE-FIBERS STUDIED BY BIREFRINGENCE AND X-RAY-DIFFRACTION MEASUREMENTS J MOL BIOL 210 113-126, 1989
PECKHAM M; WOLEDGE RC LABILE HEAT AND CHANGES IN RATE OF RELAXATION OF FROG MUSCLES J PHYSIOL-LONDON 374 123-135, 1986
ELZINGA G; PECKHAM M; WOLEDGE RC THE SARCOMERE-LENGTH DEPENDENCE OF THE RATE OF HEAT-PRODUCTION DURING ISOMETRIC TETANIC CONTRACTION OF FROG MUSCLES J PHYSIOL-LONDON 357 495-504, 1984