A genealogy of the embodied theatre practices of Suzanne Bing and Michael Chekhov: the use of play in actor training

This project investigates the previously unrecognised significance of the ways in which the Embodied Theatre practices of Suzanne Bing (1885-1967) and Michael Chekhov (1891-1955) utilised forms of what I term Embodied Play as a constituent part of their actor training processes. A methodology is developed in the introduction which draws on Foucault’s notion of genealogy and Feminist approaches to historiography in order to trace and review accounts of these often marginalised play practices in order to re-configure the contributions of Bing and Chekhov in historical terms. It also challenges notions of authenticity and singular ‘ownership’ of technique by considering the importance of collaborative cross-fertilisation with other practitioners. This research includes a broader exploration of the literature, histories and discourses about the variety of practices that are often problematically classified as Physical Theatre in relation to the identification of the key components of Bing and Chekhov’s pedagogy. The first chapter presents this mapping in tandem with the argument that McDermott’s term of Embodied Theatre is more appropriate for Bing and Chekhov’s practice. The second chapter further refines the frame of analysis to Embodied Play. Chapters three and four consider how Chekhov and Bing respectively used forms of Embodied Play. Chapter five considers how Bing and Chekhov extended their methods of Embodied Play in training which led to radical approaches to working collaboratively with text and writers. It concludes that this movement from the use of play solely for the acquisition of discrete skill or character creation to extended forms of Embodied Play enabled them to train actors to work as empowered creators of small-scale performance in their Schools/Studios, and ultimately to engage in devising processes for professional productions. Consequently, this helps to fill the gap in scholarship on the early experiments in devised Embodied Theatre. In conclusion the focus on Bing addresses the either inadequate, or absent, analyses of her practice in many of the existing historical studies which are dominated by the patrilineal narratives of Jacques Copeau and Michel Saint-Denis. The consideration of Chekhov’s practice also challenges the current discourse on play centring on Le Jeu and presents the argument for an expanded term able to consider different artists not just those from the French male lineage. Concurrently, this focus on Chekhov’s use of Embodied Play has added to the scholarship on his pedagogic and theatre-making practices

Development of fluorescent and class selective HDAC Inhibitors

 The inhibition of HDAC enzymes has proven beneficial for the treatment of a variety of diseases including cancer. This thesis details the development of class selective and fluorescent HDAC inhibitors for cellular imaging. Increased HDAC and anticancer activities were observed, and the fluorescent inhibitors were readily visualised in live cells

On-Command Regulation of Kinase Activity using Photonic Stimuli

The underlying role that many kinases play in complex cellular pathways as well as disease remains unclear. To better understand the role that kinases play in both health and disease states, the use of light as an external stimulus to modulate kinase activity with high spatiotemporal resolution has gained increasing interest over the years. Herein we highlight the progress made towards the development of light-responsive kinase enzymes and small molecule inhibitors. In these examples, photolabile caging groups and photoswitchable entities have been utilised to modulate either kinase activation or inhibition in a light-controlled manner

A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding

The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm

Shining New Light on the Spiropyran Photoswitch: A Photocage Decides between cis-trans or Spiro-Merocyanine Isomerization

Photochromic molecules from the spiropyran family are known to undergo light-induced interconversion between the colorless spiro- and the colored merocyanine forms. Here, we show for the first time that small structural modifications open up for an additional photoisomerization mode: reversible cis–trans isomerization of the merocyanine. Moreover, the introduction of a photocage allows for light-activated switching between the two modes

Design and development of photoswitchable DFG-Out RET kinase inhibitors

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline “head” constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC50) ratio in the cellular assay, tentatively assigned to stability issues. The corresponding stilbene compound gave a Z/E (IC50) ratio well above 100, consistent with that measured in the biochemical assay. Ultimately, a 7-azaindole based photoswitchable DFG-out kinase inhibitor was shown to display more than a 10-fold difference in bioactivity between the two isomers, in both a biochemical and a cell-based assay, as well as excellent stability even under reducing conditions

A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging

Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies