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SUMMARY:Evading ageing: Mitochondrial and proteostatic adaptations in oocy
 tes - Dr Elvan Böke\; Centre for Genomic Regulation
DTSTART:20231010T123000Z
DTEND:20231010T133000Z
UID:TALK205702@talks.cam.ac.uk
CONTACT:Bobbie Claxton
DESCRIPTION:Female germ cells\, oocytes\, have the remarkable ability to s
 urvive for long periods of time\, up to 50 years in humans\, while retaini
 ng the ability to give rise to a new organism. We know surprisingly little
  about the molecular mechanisms through which oocytes alleviate cellular a
 geing\, and why such mechanisms eventually fail with advanced age. My lab 
 studies longevity mechanisms and their regulation in dormant oocytes. Here
 \, I will talk about two of our recent discoveries that could partially ex
 plain the remarkable longevity of oocytes: - We have revealed oocyte dorma
 ncy involves mitochondrial activity without generation of Reactive Oxygen 
 Species (ROS). We discovered that vertebrate (frog and human) oocytes disp
 ense with mitochondrial complex I\, one of the major ROS generators in the
  cell\, while keeping the rest of the oxidative phosphorylation system act
 ive. This dramatic modulation of mitochondrial architecture enables low mi
 tochondrial activity to keep mitochondria polarized to support production 
 of essential biomolecules while avoiding ROS (Rodríguez-Nuevo et al\, Nat
 ure\, 2022). - We discover that\, surprisingly\, mouse oocytes accumulate 
 protein aggregates even in young\, healthy individuals. These aggregates a
 re sequestered within specialised compartments that we named EndoLysosomal
  Vesicular Assemblies (ELVAs). ELVAs are non-membrane-bound compartments c
 omposed of endolysosomes\, autophagosomes and proteasomes. We found that E
 LVAs do not have degradative activity in early\, immature oocytes and sequ
 ester aggregated proteins during oocyte growth. ELVAs gain degradative cap
 acity at the final stages of oocyte growth\, and degrade protein aggregate
 s. Thus\, ELVAs ensure the passage of an aggregate-free cytoplasm to the e
 arly embryo while optimising for resources in the oocyte and the early emb
 ryo (Zaffagnini et al.\, in revision).\n\nOne of the biggest problems deve
 loped nations face is late-motherhood and associated fertility problems du
 e to ageing oocytes. More than 25% of female fertility problems are unexpl
 ained\, pointing to a huge gap in our understanding of female reproduction
 . Elvan’s lab strives to help fill this gap by studying the molecular me
 chanisms through which oocytes evade ageing for decades\, and why these st
 rategies eventually fail with advanced maternal age. Elvan completed her u
 ndergraduate degree in Molecular Biology and Genetics in her native Turkey
  in 2008. She received her postgraduate training in the UK (PhD in biomedi
 cine at the CRUK-Manchester Institute) and in Boston\, USA (postdoc in the
  department of Systems Biology at Harvard Medical School). She started her
  laboratory “Oocyte Biology and Cellular Dormancy” at CRG in 2017. Elv
 an received several international and national honours\, including the Eur
 opean Research Council Starting Grant in 2017\, the Consolidator Grant in 
 2022 and an EMBO Young Investigator Award in 2021.
LOCATION:Kings Hedges Room\, Babraham Research Campus
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