Understanding structure-function relationships in the primary cilium using high content screening and super resolution microscopy

Career overview

Professor Michelle Peckham graduated in Biology (Physiology of Organisms) from the University of York in 1981 and completed a PhD with Professor Roger Woledge in the Physiology Department at University College London, focusing on the energetics of muscle contraction, which she was awarded in 1984. Following her PhD, she briefly worked with Professor Woledge before moving to the Biophysics Department at King''s College London, where she collaborated with Professor Malcolm Irving from 1985 to 1987 to demonstrate the use of birefringence as a reporter of myosin cross bridge orientation in skeletal muscle. She then worked at the University of California, San Francisco, from 1987 to 1988, before returning to the Biology Department at the University of York to work with Professors David White and John Sparrow on insect flight muscle kinetics from 1988 to 1990. During this time, she engineered mutations in contractile proteins into flight muscle actin and employed advanced biophysical measurements to assess their effects on contraction, resulting in a publication in Nature in 1990. In 1990, she was awarded a Royal Society University Research Fellowship and moved to the Biophysics Department at King''s College London, where she established her own laboratory and began using molecular biology and cell culture techniques to study the cytoskeleton in cultured muscle cells. In 1997, she joined the University of Leeds as a Lecturer, progressing through the ranks to Senior Lecturer, Reader, and ultimately Professor in 2010. Her research interests expanded to include imaging and confocal microscopy, particularly developing super-resolution techniques at Leeds over the past 5 to 10 years, including the creation of Affimers for STORM imaging. Her work has also encompassed structural biology, notably the discovery and characterisation of single alpha helices in proteins, and her laboratory recently solved the structure of the shutdown state of myosin using Cryo-EM. Professor Peckham has trained over 40 postgraduate and postdoctoral researchers and served as the president of the Royal Microscopical Society from 2016 to 2019. She is currently the Executive Honorary Secretary of the RMS and a Wellcome Trust Investigator, focusing on the regulation of motor protein activity.

Research interests

Professor Peckham''s research focuses on the cytoskeleton, specifically investigating how myosins and other motor proteins function within cells and how mutations in cytoskeletal proteins can lead to disease. The laboratory employs a variety of techniques, including Cryo-electron microscopy (Cryo-EM), confocal microscopy, super-resolution imaging, and biochemical and biophysical methods to explore these areas. Significant contributions include solving the structure of the shutdown state of smooth muscle myosin, which was published in Nature in December 2020, revealing insights into how myosin transitions to this state and the role of phosphorylation in its activation. The laboratory has developed advanced imaging systems, such as a 3D PALM/STORM system and an instant structured illumination microscope (iSIM), enhancing the ability to conduct live cell imaging and achieve resolutions significantly better than conventional methods. Professor Peckham''s work also extends to collaborations aimed at developing small non-antibody binding proteins known as Affimers for improved super-resolution imaging of cytoskeletal proteins. Recent studies have utilised stimulated emission depletion (STED) microscopy to investigate structural changes in Z-discs in diseased hearts, with findings published in Frontiers in Cardiovascular Medicine in 2023. Research interests encompass the roles of myosins in diseases, including cancer, where specific myosins are found to be overexpressed in prostate cancer, and the differentiation of muscle cells in culture, focusing on the organisation of the cytoskeleton. Current PhD projects in the lab include the use of artificial intelligence to analyse super-resolution microscopy images, the development of Affimers for visualising myosins, and the impact of heart muscle diseases on protein organisation. Overall, Professor Peckham''s research integrates structural biology, advanced imaging techniques, and molecular biology to further understand the cytoskeleton''s role in health and disease.