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DTSTAMP:20240112T101816Z
DTSTART:20240123T130000Z
DTEND:20240123T140000Z
SUMMARY:Advances in Biosciences Seminar: Speaker\, Dr Christo Pliotas\, U
 niversity of Manchester - Title: "Exploring the conformational ensembles
  of mechanosensitive ion channels by EPR spectroscopy"
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DESCRIPTION:Hearing and touch\, the Venus flytrap and osmotic pressure se
 nsing are all consequences of the pervasive ability of ion channels to s
 ense forces. Mechanosensitive ion channels occur in organisms as diverse
  as microbes and humans\, and serve a range of vital functions\, often e
 nabling responses to adverse environmental stimuli. Although they are st
 ructurally diverse\, they share a common mechanism\, that of sensing and
  response to membrane tension. Several models have been proposed\, but t
 heir underlying principle is unknown. A major hurdle in the study of mec
 hanosensitive is the lack of molecular triggers for mimicking force gene
 ration in membranes to stabilise their functional states. Electron Param
 agnetic Resonance (EPR) spectroscopy has emerged as a powerful tool for 
 assessing protein conformation\, folding\, oligomerisation and dynamics.
  EPR distance measurements provide high resolution quantitative informat
 ion on the equilibria of proteins\, dovetailing well with techniques suc
 h as Xray crystallography and CryoEM. An inherent limit placed on membra
 ne protein studies is the need to remove the protein from its natural me
 mbrane environment. However\, recent developments provide lipid scaffold
 s that mimic that environment and offer flexibility of choice in lipid c
 omposition\, while EPR measurements on proteins could also be performed 
 in cells. Here\, we will focus on the application of EPR spectroscopy in
  the study of integral membrane proteins\, highlighting two recent case 
 studies from our lab. The first explores an allosteric mechanism that re
 gulates mechanosensitive ion channels1\,2\, and the second elucidates th
 e effect antibiotics have on the conformation of the BAM complex\, with 
 measurements performed in intact cells3. \n1.	Kapsalis C\, Wang B\, El M
 kami H\, Pitt SJ\, Schnell JR\, Smith TK\, Lippiat JD\, Bode BE\, Pliota
 s C (2019) Allosteric activation of an ion channel triggered by modifica
 tion of mechanosensitive nano-pockets. Nature Communications 10: 46192\n
 2.	Wang B\, Lane BJ\, Kapsalis C\, Ault JR\, Sobott F\, El Mkami H\, Cal
 abrese AN\, Kalli AC\, Pliotas C (2022) Pocket delipidation induced by m
 embrane tension or modification leads to a structurally analogous mechan
 osensitive channel state. Structure 30: 608 622 e605\n3.	3. Haysom SF\, 
 Machin J\, Whitehouse JM\, Horne JE\, Fenn K\, Ma Y\, El Mkami H\, Bohri
 nger N\, Schaberle TF\, Ranson NA\, Radford SE\, Pliotas C (2023) Daroba
 ctin B Stabilises a Lateral-Closed Conformation of the BAM Complex in E.
  coli Cells. Angewandte Chemie International Edition 62: e202218783 \n\n
 Short Bio:\nChristos Pliotas obtained a BSc (Hons) in Physics from the U
 niversity of Athens\, an MSc in Medical Physics and a PhD in Biochemistr
 y from the University of Aberdeen. He did his postdoc at the University 
 of St Andrews with James H. Naismith FRS focusing on the structural biol
 ogy of membrane proteins and in 2016 he was awarded an independent 5-yea
 r Fellowship from the Royal Society of Edinburgh to start his own group 
 at the Biomedical Sciences Research Complex\, University of St Andrews. 
 Christos moved to the Astbury Centre for Structural Molecular Biology\, 
 University of Leeds in October 2018\, as a Lecturer in Integrative Membr
 ane Biology. During his time in Leeds\, he secured funding from BBSRC to
  lead multiple projects\, including a New Investigator Award (2019)\, wh
 ile he received the Sir Robin MacLellan Award for outstanding research b
 y Tenovus (2022). As of June 2023\, Christos moved to the Division of Mo
 lecular and Cellular Function\, School of Biological Sciences\, Faculty 
 of Biology\, Medicine and Health\, at the University of Manchester\, to 
 take up a post as a Reader in Structural Biological EPR Spectroscopy. In
  Manchester\, Christos will launch the new BioEmPiRe Centre for Structur
 al Biological EPR Spectroscopy in the Michael Smith building\, in early 
 2024. Christos is currently a committee member of the Royal Society Newt
 on Fellowships for Biological Sciences\, a committee member of the Royal
  Society of Chemistry ESR Group and a Fellow of the Royal Society of Bio
 logy (FRSB).\n\n
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Michael Smith Lecture Theatre\, Michael Smith Building\, Manches
 ter
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