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
- President of the 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 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 also working with Stefan Kepinski on gravitropism in plants (BBSRC funded) and with Colin Johnson on primary cilia (BBSRC funded).
We are funded by the British Heart Foundation to investigate how mutations in slow (beta-cardiac) myosin heavy chain in the coiled-coil cause heart disease. 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 have also recently built a simple light sheet microscope (Open SPIM).
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), super-resolution imaging of primary cilia (with Colin Johnson in the faculty of medicine and health), investigating 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, 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.
Research groups and institutes
- Cell and Organismal Biology
- Structural Biology