Professor Michelle Peckham

Professor Michelle Peckham

Responsibilities

  • Executive Honorary Secretary, Royal Microscopical Society

Research interests

Myosins, motors, and muscle in health and disease.

Our laboratory is interested in the cytoskeleton, from basic research into how myosins perform their functions in cells, to how mutations in cytoskeletal proteins cause disease.

We recently discovered that many different types of myosin are overexpressed in prostate cancer and this contributes to the cellular phenotype and metastatic potential (Makowska et al., Cell Reports, 2015). The image below shows how the cytoskeleton changes when different myosin isoforms are depleted (from left to right: wild type cells, Myo1b, Myo9b, Myo10 and Myo18a knockdown cells: cells are stained for actin (red) and non-muscle myosin 2A (green)).

Michelle Peckham

We are also interested in how muscle cells differentiate in culture - and how they can organise the cytoskeleton into beautifully regular structures, as show here for a cultured human skeletal myotube, stained for skeletal myosin (green).

Michelle Peckham

We have a very strong interest in imaging, including super-resolution imaging. We have built a 3D PALM/STORM system, that allows a resolution of ~10nm (about 20 times better than a normal wide-field microscope), and an iSIM (instant structured illumination microscope) which is very good for fast live cell imaging. The image below shows a 3D STORM image of the actin cytoskeleton in a cell.

Michelle Peckham

We are collaborating with Darren Tomlinson's group to raise small non-antibody binding proteins (~12kDa in size) called Affimers to cytoskeletal proteins, to improve our super-resolution imaging, and have also a range of Affimers to different proteins including tubulin (recently published in E-life: Tiede et al., 2017; Lopata et al., Sci. Reports 2018).

We are funded by BBSRC to use super-resolution microscopopy (PALM/STORM) to uncover the organisation of proteins in the striated muscle Z-disc, exploiting the use of Affimers, and in a second grant, to investigate protein organisation in primary cilia (with Colin Johnson, FMH).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 have also recently built a simple light sheet microscope (Open SPIM). MRC is funding us to investigate mutations in non-muscle myosin 2A and the underlying reason for these mutations to result in blood disorders, and to investigate mutations in skeletal and cardiac myosin, to understand how these result in heart and skeletal muscle diseases (the latter with Julien Ochala, at KCL). PhD students in the lab are also studying aspects of these problems, including cryo-EM and modelling of myosin 5 (Wellcome Trust funded, with Ste Muench and Sarah Harris (MAPS)), using super-resolution microscopy, crystallography and electron microscopy to study  ASPM, a protein involved in mitosis (With Jacqueline Bond in the faculty of Medicine and Health), and investigating muscle satellite cells (with Stuart Eggington in FBS).

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 (including high resolution Cryo-EM), 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.

The Astbury Centre for Structural Molecular Biology

<h4>Research projects</h4> <p>Any research projects I'm currently working on will be listed below. Our list of all <a href="https://biologicalsciences.leeds.ac.uk/dir/research-projects">research projects</a> allows you to view and search the full list of projects in the faculty.</p>

Qualifications

  • BA, York; PhD 1984, London.

Professional memberships

  • Fellow of the Royal Microscopical Society
  • Member of British Society for Molecular Biology
  • Fellow of the Royal Society for Biology

Student education

Undergraduate project topics:

  • Imaging, Microscopy, cytoskeleton, diseases linked to cytoskeletal proteins (including proteins in the muscle cytoskeleton)

Postgraduate studentship areas:

  • PhD opportunities in the cytoskeleton, roles of cytoskeletal proteins in disease - including cardiac myosin heavy chain mutations that cause heart disease, mutations in non-muscle myosin 2A that causes bleeding disorders, mutations in myosins related to other diseases such as deafness and blindness. Role of the cytoskeleton in cancer. Super-resolution imaging.  I am a BHF 4 year programe PhD supervisor

See also:

Research groups and institutes

  • Cell and Organismal Biology
  • Structural Biology

Current postgraduate researchers

<h4>Postgraduate research opportunities</h4> <p>We welcome enquiries from motivated and qualified applicants from all around the world who are interested in PhD study. Our <a href="https://phd.leeds.ac.uk">research opportunities</a> allow you to search for projects and scholarships.</p>
Projects
    <li><a href="//phd.leeds.ac.uk/project/428-exploring-the-mitotic-functions-of-aspm-in-human-brain-size-regulation">Exploring the mitotic functions of ASPM in human brain size regulation</a></li> <li><a href="//phd.leeds.ac.uk/project/332-unpicking-how-myosin-and-myosin-binding-protein-c-cause-heart-disease">Unpicking how myosin and myosin binding protein C cause heart disease</a></li>