Professor Michelle Peckham
- Position: Professor
- Areas of expertise: Cytoskeleton; actin; myosin; molecular motors; myosin; kinesin; Microscopy; super-resolution imaging; electron microscopy; biochemical techniques
- Email: M.Peckham@leeds.ac.uk
- Phone: +44(0)113 343 4348
- Location: 8.106 Astbury
- Website: Contractility Group | Twitter | LinkedIn | Googlescholar | Researchgate | ORCID
- Executive Honorary Secretary, Royal Microscopical Society
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)).
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).
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.
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.
- BA, York; PhD 1984, London.
- Fellow of the Royal Microscopical Society
- Member of British Society for Molecular Biology
- Fellow of the Royal Society for Biology
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
- Faculty Graduate School
- FindaPhD Project details:
Research groups and institutes
- Cell and Organismal Biology
- Structural Biology
Current postgraduate researchers
<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>