Faculty of Biological Sciences

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, email address for  

You can read more about Prof Peckham's interests here:
www.contractility.org

Research Interests

Myosins, motors, and muscle in health and disease

Current Projects

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



Studentship information

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.

See also:

Modules managed

BIOL2211 - Human Diseases

Modules taught

BIOC1301 - Introductory Integrated Biochemistry: the Molecules and Processes of Life
BIOC3111/12/BIOL3112 b - ATU - Cell motility & trafficking
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOL2211 - Human Diseases
BIOL3306 - Biological Sciences Research Project
BIOL5112M/5312M - Bioimaging
BIOL5294M - MSc Bioscience Research Project Proposal
BIOL5312M - Bioimaging
BIOL5392M - Bioscience MSc Research Project
BMSC3101 - Inherited Disorders
DSUR1127 - Health and Health promotion
MICR2120/BIOC2301 - Integrated Biochemistry/Medical Bacteriology
MICR3110 - Medical Microbiology Research Project

Centre memberships:

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 Marcin Wolny  (Research Fellow)


Postgraduates

Christopher Bartlett  
Glenn Carrington [bs10g3c]  
Sophie Hesketh  
Ruth Hughes [RPG]  
Anna Lopata  
Katarzyna Makowska  
Rebecca Perrin [RPG]  
Brendan Rogers