Faculty of Biological Sciences

Prof Michelle Peckham

BA, York; PhD 1984, London.
Professor of Cell Biology
School of Molecular and Cellular Biology

Background: 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.

Contact:  Astbury 8.106, +44(0) 113 34 34348, email address for  

You can read more about Prof Peckham's interests here:
www.contractility.org

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.

For example, 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)).

 prostate cancer cells

We collaborate with a company (Orla Protein Technologies) to develop new methodologies to better differentiate muscle cells in culture, which helps us investigate the effects of mutations in muscle sarcomeric proteins on disease (see our recent paper in Cytotechnology, 2016, Parker et al.)  The image below shows a human skeletal myotube differentiated on an Orla Surface, stained for skeletal myosin (green).

myotube in culture

 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.

super-resolution image

 

We are also interested in the structure and regulation of cytoskeletal proteins, recently obtaining crystal structures of the calponin homology domains of alpha-actinin, both wild type and mutated isoforms (see Haywood et al., 2016, Biochem. J.) And we are starting to use other structural approaches (Cryo-EM and NMR) to investigate protein structure.

 

Current Projects

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), and investigating ASPM, a protein involved in mitosis (With Jacqueline Bond in the faculty of Medicine and Health).

 

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

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

Postgraduate studentship areas:

  • We have a PhD studentship opportunity currently available
  • (see https://www.findaphd.com/search/phd.aspx?keywords=Peckham)
  • This isa directly funded BBSRC iCASE studentship with Orla Protein Technologies (closing date Monday 8th March 2017): Developing and optimising defined tissue culture surfaces for cellular differentiation of muscle.
  • This project will investigate novel ways to differentiate skeletal and cardia muscle differentiation in culture using novel surfaces, and tissue engineering. Working with Orla, the student will generate new peptides to support and promote differentiation, and we will generate patterned surfaces, and being to work on differentiation in 3D. The project will use a range of light microscopy imaging to assess differentiation, including some 'super-resolution' microscopy and light sheet microscopy.
  • Find out more about our super-resolution microscopy here:
  • https://www.youtube.com/watch?v=_mtLqKxq8Ig

See also:

Modules managed

BIOL2211 - Human Diseases

Modules taught

BIOC1301 - Introductory Integrated Biochemistry: the Molecules and Processes of Life
BIOC3111/12/BIOL3112 B - ATU - Cytoskeletal Molecular Motors
BIOC3160 - Laboratory/Literature/Computing Research Project
BIOL1302 - Introductory Skills for Biological Sciences
BIOL2211 - Human Diseases
BIOL3306 - Biological Sciences Research Project
BIOL5112M/5312M - Bioimaging
BIOW5901X - Foundation module
BIOW5907X - Biocatalysis
BMSC3101 - Inherited Disorders
DSUR1127 - Health and Health promotion
FOBS1201/BIOL1214 - Molecular Physiology/Multicellular Systems
MICR2120/BIOC2301 - Integrated Biochemistry/Medical Bacteriology
MICR3110 - Medical Microbiology Research Project

Centre memberships:

Group Leader Prof Michelle Peckham  (Professor of Cell Biology)

Myosins, motors, and muscle in health and disease 

Dr Matthew Batchelor  (Research Fellow)

Dr Sally Boxall  (Research Facility Manager)

Dr Alistair Curd  (Research Fellow)

Dr Marta Kurzawa  (Research Technician)

Dr Francine Parker  (Research Fellow)

Dr Marcin Wolny  (Research Fellow)


Postgraduates

Glenn Carrington (Primary supervisor) 50% FTE
Sophie Hesketh (Primary supervisor) 50% FTE
Marcus Holt (Primary supervisor) 60% FTE
Brendan Rogers (Primary supervisor) 34% FTE
Christopher Bartlett (Co-supervisor) 50% FTE
Anna Lopata (Co-supervisor) 50% FTE
Rebecca Perrin (Co-supervisor) 40% FTE