A novel mechanism of selective inhibition of Glycine receptors observed by Cryo-EM | Controlling and combining signal activation for adhesion and receptor bridging

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• Speaker to be confirmed
• Friday 17 November 2023, 12:30-13:30
• Seminar Room (Level 2), Dept of Pharmacology .

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Dr Stephanie Nestorow (Miller lab), Department of Pharmacology, University of Cambridge

Biography

Dr Nestorow completed their PhD at the University of Birmingham under the guidance of Professor Tim Dafforn focusing on using SMAL Ps for the polymer purification of difficult membrane proteins. During her PhD, their research focused on the development and characterisation of several novel polymers which were then utilised to study membrane proteins of agrochemical significance. During the PhD, they gained an aptitude for a variety of biochemical and biophysical techniques to investigate protein structure and function.

Based on her experience purifying and characterising membrane proteins, they began my post-doc position within the Miller lab in December 2023. During their first year in the Miller lab, they worked on both GABA and glycine receptors. Her current research focuses on firstly, using Cryo-EM based structural techniques to decipher novel mechanisms of selective inhibition of Glycine receptors. Secondly, studying the structural basis of small molecule and toxin/antibody modulation of GABA receptors.

Dr Anthony Keeble (Howarth lab), Department of Pharmacology, University of Cambridge

Biography

Anthony did a PhD and post-doc with Professor Colin Kleanthous first at the University of East Anglia and then at the University of York where he applied biochemical and biophysical approaches to understand the mechanisms of inhibitor binding to protein toxins. Subsequently, Anthony used a combined structural, biochemical, and biophysical approach to understand immune receptor complex formation. Anthony used these studies to: (i) characterise the interactions of TRIM21 , a novel intracellular IgG receptor, with antibodies at the Laboratory of Molecular Biology, Cambridge working with Dr Leo James; (ii) characterise the formation and mechanism of activation of the activating complexes of the classical (C1qrs) and lectin (MBL-MASP) pathways of complement at the Department of Respiratory Sciences, University of Leicester working with Professor Russell Wallis; (iii) characterise the mechanism of formation of receptors (FceRI and CD23 ) with the allergy related antibody IgE, as well as the influence of anti-IgE Fab binding at the Randall Division of Cell and Molecular Biophysics, King’s College London working with Professor Brian Sutton and Professor James McDonnell. Anthony is now working with Professor Mark Howarth within the Department of Pharmacology, University of Cambridge developing the novel protein coupling reagents: SpyTag/SpyCatcher, SnoopTag/SnoopCatcher, DogTag/DogCatcher, SnoopLigase, as well NeissLock that have a wide-range of applications: vaccines targeting COVID , malaria, and HIV ; split chimeric antigen receptor-modified T cells, protein hydrogels, construction of antibody like molecules with controlled architectures, labelling bacterial outer membrane proteins to measure membrane dynamics, as well as selective labelling mammalian ion channels.

Zoom link: https://zoom.us/j/92268391484?pwd=ajBET1FHbUJJWEdzL1hQWkREcFFRZz09 Meeting ID: 922 6839 1484 Passcode: CeWtVvM68d

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