BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Achieving Redox Signalling specificity through Spatiotemporal and 
 Chemical approaches - Dr Tobias Dansen | UMC Utrecht 
DTSTART:20190911T140000Z
DTEND:20190911T150000Z
UID:TALK118633@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:Redox signalling is a form of signal transduction that starts 
 with the production of hydrogen peroxide and proceeds through the reversib
 le oxidation of cysteine-thiol side-chains of proteins. It is clear that r
 edox signalling leads only to oxidation of very specific proteins\, but th
 is is in apparent conflict with the chemical simplicity of H2O2. Furthermo
 re\, most cysteines found to play a role in redox signalling have a relati
 vely low reactivity to H2O2 compared to the catalytic cysteines in dedicat
 ed H2O2 scavenging enzymes. It is therefore not surprising that understand
 ing how specificity and reactivity of Cysteine oxidation is being achieved
  in redox signalling is arguably the biggest question in the field. Recent
  studies have described cases in which Peroxiredoxins\, dedicated H2O2 sca
 vengers\, after oxidation can partake in a redox relay reaction to oxidise
  cysteines in a client protein. We have undertaken extensive quantitative 
 mass-spectrometry studies that suggest that 1) Peroxiredoxin mediated redo
 x relay is a wide-spread phenomenon\, 2) Each of the five human 2-Cys pero
 xiredoxins have a preferred set of targets for the redox relay reaction an
 d 3) redox relay can take place by two distinct molecular mechanisms that 
 could aid in the cellular response to different levels of H2O2.\nAnother l
 ayer of specificity in redox signalling that has been proposed is through 
 spatiotemproral control of H2O2 production by for instance mitochondria\, 
 but good model systems to study this have been lacking. Cell polarization 
 requires the dynamic regulation of signaling cascades in both time and spa
 ce\, making it an attractive model to study localized\, subcellular (redox
 )signalling. We take advantage of this and use the C. elegans early embryo
 \, one of the most-studied systems for cell polarization\, to analyze the 
 spatiotemporal regulation of redox signaling. We find that\, coinciding wi
 th polarization\, a subgroup of mitochondria relocates to the cell membran
 e at the site of symmetry breaking. After this\, mitochondria become highl
 y motile and localize closely to the posterior cortex of the embryo. An ul
 trasensitive H2O2 -specific sensor that we optimized for live imaging in C
 . elegans shows that mitochondrial relocation to the cell membrane is acco
 mpanied by a striking increase in cortical H2O2 –levels. Furthermore\, m
 itochondrial H2O2 directly influences polarization\, since compounds that 
 alter mitochondrial H2O2 -production affect symmetry breaking and maximal 
 polarization. Our observations show that redox signalling can indeed be in
 itiated by the local production of H2O2\, and that cell polarization is re
 gulated by redox signalling.\nCollectively these data suggest that redox s
 ignalling specificity can be regulated both by differences in the chemical
  properties of peroxiredoxin-mediated redox-relay targets and by spatiotem
 poral control of H2O2 production. 
LOCATION:Sackler Lecture Theatre (Level 7) The Keith Peters Building\, Cam
 bridge Biomedical Campus
END:VEVENT
END:VCALENDAR