... understanding life in molecular detail

Prof Michelle Peckham

Myosins, molecular motors, structure, imaging, muscle, microtubules, Affimer, super-resolution, Electron Microscopy

We have broad interests in molecular motors (myosins and kinesins), how their activity is regulated, and how they carry out their cellular functions. We are also investigating how mutations in several of these proteins contribute to a range of diseases, using expressed and purified proteins, and cultured muscle cells in our investigations. We are developing super-resolution imaging (SIM, PALM) as tools to investigate muscle protein organisation. We are developing Affimer technology for super-resolution imaging, and for detecting specific protein conformations and post-translational modifications for actin and microtubules. We are using negative stain and Cryo-EM to investigate myosin structure.

Current major projects include:
  • How disease mutations affect protein structure and function in myosins
  • How myosins play a role in the development of metastasis in cancer
  • Using super-resolution imaging techniques (PALM, dSTORM, iSIM) to image the cytoskeleton
  • Determining the structure and function of myosins using Cryo-EM

The cytoskeleton (actin filaments and microtubules) are precisely organised in cells.  For example, in muscle, actin and myosin are organised into muscle filaments to power contraction, whereas in non-muscle cells, the actin cytoskeleton is much less well organized, is more dynamic, and these cells contain many different kinds of myosins. The contrast between the organisation and regulation of the cytosksleton between highly ordered striated muscle, and crawling cells is a fascinating one.  Similarly, the organisation of microtubules, and the expression of tubulin isoforms and post-translational modifications (the tubulin code) is highly dependent on the type of cell and tissue they are observed in. Mutations, or changes to expression levels for these types of proteins are often important in the development of a wide range of diseases.

Our laboratory uses a wide range of techniques to study muscle differentiation, cancer cell behaviour,  the cytoskeleton and myosins including bio-imaging, live cell imaging, protein biochemistry, electron microscopy, crystallography, and a wide range of cell and molecular biological techniques. Collaborations within and beyond the Faculty and the University have involved electron microscopy, crystallography, optical tweezers, Total Internal Reflection Fluorescence (TIRF) microscopy and most recently super-resolution microscopy. We have built our own 3D PALM/STORM microscope and can image the organisation of proteins in a wide range of cellular structures using this approach to ~5nm precision.

Research Projects:

Structure, function, regulation and mutataions in Myosin 2 

Our lab is interested in the structure and function of myosin 2. As part of this, we investigate the effects of mutations in beta-cardiac myosin that cause heart disease. We are also interested in mutations in non-muscle myosin 2a, which result in bleeding disorders.  How do these mutations affect the structure, function and regulation of these myosins?

To answer these questions, we use a combination of techniques. These include circular dichroism to determine effects on secondary structure, assessing the cellular effects by  expressing GFP-tagged myosin in cultured muscle cells, to find out how well the mutant myosin incorporates into muscle sarcomeres, expression and purification of myosin domains and the use of negative stain and Cryo-EM to determine the effects of mutations on structure.  

PALM and dSTORM to understand protein organisation in complex structures.

We use PALM and dSTORM to investigate the detailed organisation of proteins in structures that are difficult to evaluate by conventional light or electron microscopy. In one of these projects, we are using this approach to investigate the Z-disc, a narrow (~100nm wide) structure found at the ends of muscle sarcomeres. Its narrow size means that conventional light microscopy is unable to reveal the detailed organisation of proteins within the Z-disc as this is below the resolution limit (~250nm). And yet it contains ~50 different important signalling and structural proteins.  How are these proteins organised with respect to each other?  To answer this question, we use PALM and dSTORM to determine their organisation.  Similarly, we are working with Prof. Colin Johnson (St James) to uncover the organisation of proteins within primary cilia. These fine structures are important signalling centres on the apical surfaces of cells, but we know very little about how proteins are organised within them. To help us with both of these projects, we are developing Affimers to specifically label proteins in dSTORM, as their small size means better penetration and resolution in our final images.

Understanding the Tubulin Code

Microtubules are made up of diverse forms of tubulin, and many different types of post-translational modifications (PTMs), the so-called tubulin code.  However, it is unclear what all the different PTMs are for, or how they affect the structure and function of microtubules.  We are developing new tools (Affimers) that we think can discriminate between different types of tubulin, as a way of trying to understand how, where and when tubulin isoforms vary, and what effect this has on their cellular roles, and as a potential approach to isolating specific subsets of microtubules, to determine their specific properties. This is particularly important in the brain, which is full of many different types of tubulin and PTMs, and likely important in ageing and neurodegeneration. 


Detailed research programme                  Close ▲

Professor of Cell Biology
BA (York) PhD (UCL)

Royal Society University Research Fellow (KCL) 1990 - 1997
Lecturer (Leeds) 1997 - 2003
Senior Lecturer (Leeds) 2003 - 2007
Reader in Cell Biology (Leeds) 2007 รข?? 2010

Astbury 8.106
School of Molecular and Cellular Biology
0113 343 4348


Selected Publications

  1. Lambacher, M.J., Bruel, A-L. van Dam, T. J. P, Szyma?ska, K., Slaats. G.G., Stefanie Kuhns, S., McManus, G.J., Kennedy, J.E., Gaff, K., Wu, K.M., Van der Lee, R., Burglen, L., Doummar, D., Rivière,J.B., Faivre, L., Attié-Bitach, T., Saunier, S., Curd, A., Peckham, M., Giles, R., Johnson, C.A., Huynen, M.A., Thauvin-Robinet, C., Blacque, O.E. (2016) TMEM107 recruits ciliopathy proteins to anchored periodic subdomains of the ciliary transition zone membrane and is mutated in Joubert syndrome.  Nature Cell Biology 18: 122-31

  2. Makowska, K.A., Hughes, R.E., White, K.J., Wells, C.M., Peckham, M. (2015) Myo1b, Myo9b, Specific myosins control actin organization, cell morphology and migration in prostate cancer cells.  Cell Reports 13:2118-25

  3. Parker, F., Batchelor, M., Wolny, M., Hughes, R., Knight, P. J., and Peckham, M. (2018) A1603P and K1617del, Mutations in beta-Cardiac Myosin Heavy Chain that Cause Laing Early-Onset Distal Myopathy, Affect Secondary Structure and Filament Formation In Vitro and In Vivo. J Mol Biol430, 1459-1478

  4. Lopata, A., Hughes, R., Tiede, C., Heissler, S. M., Sellers, J. R., Knight, P. J., Tomlinson, D., and Peckham, M. (2018) Affimer proteins for F-actin: novel affinity reagents that label F-actin in live and fixed cells. Sci Rep8, 6572