... understanding life in molecular detail

Prof Michelle Peckham

Myosins, molecular motors, structure, imaging, muscle

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.

Current major projects include:
  • How disease mutations alter the coiled coil in cardiac myosin
  • Contribution of myosins to the metastatic process in cancer
  • Development of super-resolution imaging techniques (PALM, iSIM)
  • Functional properties of stable single alpha helices

Striated muscle contains a beautiful almost crystalline array of proteins organized with great precision into muscle sarcomeres, packed end to end in myofibrillar arrays. In each sarcomere, actin is organized into thin filaments and myosin into interdigitating thick filaments. Myosin crossbridges interact with actin in the thin filaments to generate force and filament sliding. The precise organization of the filaments into muscle sarcomeres is key for the heart and skeletal muscle to contract normally. However, we know very little about how these proteins become assembled into such precise structures, or how these structures are maintained. Muscle fibres are single cells with many thousands of nuclei, formed by the fusion of myoblasts. In non-muscle cells such as myoblasts and fibroblasts, the actin cytoskeleton is much less well organized, is more dynamic, and these cells contain many different kinds of myosins. The contrast between highly ordered striated muscle, and crawling cells is a fascinating one. We still have much to learn about how myoblasts fuse and re-organise their actin cytoskeleton to generate the precise structure found in muscle fibres. I have used a wide range of techniques to study muscle differentiation, 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.

Research Projects:


Much of my current research focuses on the properties of the different myosins, to understand how they are regulated and how they perform their cellular functions. Myosins are molecular motors, in which the motor domain contains an actin and nucleotide binding site, and the tail contains domains that direct the cellular role of each myosin. Myosin 2 is the original type of myosin discovered in skeletal muscle, and also found in heart and smooth muscle.

Myosin 2 and Heart Diseaseâ?¨

Part of my research is to investigate how mutations in the tail of the heart and slow muscle myosin isoform of myosin 2, beta-cardiac myosin, results in heart disease. We use a combination of techniques, from expressing peptides from the tail domain with and without the mutation, to test how they affect structure using circular dichroism, to expressing full length GFP-tagged myosin in cultured adult rat cardiomyocytes using an adenovirus based approach, to find out how well the mutant myosin incorporates into muscle sarcomeres using live cell imaging, and FRAP, and to determine how the mutations affect contraction (BHF funded research, with Peter Knight and Ed White at Leeds).

Non-muscle myosinsâ?¨

Apart from myosin 2, there are 11 different types of myosins in humans, mostly found in non-muscle cells, which perform a variety of roles. A single cell probably expresses over 20 different isoforms. While the regulation of myosin 2 activity in striated and smooth muscle is reasonably well understood that of other myosins in non-muscle cells is less clear. How do cells regulate and co-ordinate the activity of all of their different myosins?

To start to address this important question, we recently investigated the regulation of myosin 7a. This myosin is essential for hearing as it is required to build the actin rich stereocilia on the apical surfaces of the inner and outer hair cells in the cochlea. If the stereocilia don’t form, then sound waves cannot be detected and signals transmitted from the cochlea to the brain. We discovered that myosin 7a is a monomeric myosin, which means it has a single motor domain, and the interaction between the tip of its tail with the motor domain inhibits its activity (see Figure below). Binding of other proteins to the tail could result in the activation of this myosin, and we’re starting to explore this idea using different myosin 7a binding partners (with Peter Knight at Leeds, and Jim Sellers, at NIH)

We also recently showed that myosin 7, myosin 10 and myosin 6 all contain a novel ‘single alpha helical’ or SAH domain, which is found just after the lever in each of these myosins. The lever is found just after the motor domain and it amplifies small structural changes in the motor domain that result from ATP hydrolysis into large movements. We found that the SAH domain is able to increase the functional length of the lever, resulting in larger structural changes. We are pursuing our research into the SAH domain, which is found in a wide variety of proteins as well as in myosins, to understand how it contributes to the functions of these proteins (BBSRC funded, with Peter Knight and Lorna Dougan, Leeds).

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. Curd, A., Makowska, K., York, A, Shroff, H, and Peckham, M. (2015) Construction of an instant structured illumination microscope. Methods, 88: 37-47

  4. Wolny, M., Batchelor, M., Knight, P. J., Paci, E., Dougan, L. and Peckham, M. (2014) Stable single alpha-helices are constant force springs in proteins. Journal of Biological Chemistry. 289, 27825-27835