03 JUIN 2016 - 13H

Adapting to a stressful start in life - Séminaire externe IBPS

Alex Gould, FCI, Londres, UK. alex.gould@crick.ac.uk 


Lieu : Amphithéâtre Charpak, LPNHE | Campus Jussieu


Animals often encounter stressful environments during development and so have evolved numerous different coping mechanisms. In mammals, it is known that one important strategy for surviving nutrient deprivation is to protect or spare the growth of critical organs such as the CNS at the expense of others. Previous work in our laboratory showed that this brain sparing process is also present in Drosophila and that it requires the receptor Anaplastic lymphoma kinase (Alk). Alk stimulates PI3K signalling in CNS stem cell-like progenitors called neuroblasts, regardless of whether dietary nutrients are present or absent. This is because glial cells of the neuroblast niche constitutively secrete the ligand for Alk, Jelly belly, thus freeing neuroblasts from a dependence upon nutrient-dependent growth components such as Insulinlike peptides. More recently, we have found that neuroblasts are not only highly protected from nutrient restriction but also from oxidative stress. In both cases, glial cells play a critical role but, during oxidative stress, they function to safeguard neuroblasts from damage by reactive oxygen species (ROS). Lipid droplets that form in niche glia during oxidative stress limit the levels of ROS and inhibit the oxidation of polyunsaturated fatty acids (PUFAs). These droplets protect glia and also neuroblasts from peroxidation chain reactions that can damage many types of macromolecules. Evidence suggests that the underlying antioxidant mechanism involves diverting PUFAs, including diet-derived linoleic acid, away from membranes to the core of lipid droplets, where they are less vulnerable to peroxidation. This study reveals an antioxidant role for lipid droplets that could be relevant in other biological contexts.

Alex Gould obtained his BA and MA in Natural Sciences from King's College, University of Cambridge, UK. His PhD research was on Drosophila Hox genes with Rob White at the University of Cambridge. He was then awarded a Beit Memorial Fellowship to undertake postdoctoral training on vertebrate Hox genes with Robb Krumlauf at The MRC National Institute for Medical Research (NIMR) in Mill Hill where he established his own research group in 1998. In 2012, Alex was made Head of the newly formed Division of Physiology & Metabolism at NIMR. In 2015, he became a Senior Group Leader at The Francis Crick Institute. Alex was elected to EMBO in 2008 and was awarded the Hooke Medal of the British Society for Cell Biology in 2011. He was elected to the Academy of Medical Sciences in 2013 and became a Wellcome Trust Senior Investigator in 2014. Alex sits on the Editorial Advisory Boards of Development and PLOS Biology and is a member of the Wellcome Trust Peer Review College. His current research interests include the molecular, cellular and physiological mechanisms regulating growth and metabolism.