MRC LHA at UCL Seminar
Dr Alex P. Gould
The Francis Crick Institute
Date: Thursday 9th November 16.00-17.00
Location: Christopher Ingold Building G21 Ramsay LT
Title: Coping with a stressful start in life
Summary: Developmental stresses can exert both short- and long-term influences upon physiology and metabolism. To identify underlying mechanisms, we established Drosophila models of developmental undernourishment, hypoxia and oxidative stress. Using these models, we found that the growth of the CNS is remarkably well protected against developmental stresses, compared to that of other organs. Both constitutive and stress-induced CNS adaptations serve to protect the divisions of neural stem cells (neuroblasts) and thus safeguard the numbers and diversity of their progeny neurons. The short-term protective mechanisms that we have identified in the CNS thus far include Anaplastic Lymphoma Kinase (Alk) signaling, re-wiring of target-of-rapamycin (TOR) signaling and the induction of lipid droplets with anti-oxidant properties. We have also investigated the long-term impacts of developmental undernourishment upon adult metabolism and lifespan. We observed that restricting dietary nutrients during development can, depending upon the subsequent adult environment, more than double the median lifespan of Drosophila. This developmental manipulation induces a long-term adaptive response in adult flies, which substantially alters their lipid metabolism. In particular, adults produce a less harmful blend of toxic lipids (autotoxins), which we have identified using NMR and mass spectrometry. Autotoxins are shed into the environment and so can decrease the lifespan of neighboring flies. Changes in autotoxin production and/or resistance may also contribute to the effects of other well-known regulators of lifespan. More recently, we observed that developmental exposure to low doses of pro-oxidants can also extend the lifespan of Drosophila adults. Surprisingly, this does not appear to be mediated by a hormesis-like response. We are currently testing alternative mechanisms that might underlie lifespan extensions by pro-oxidants.
Biography: 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/Royal Society Sir Henry Dale Fellowship Interview Committee. Alex's current research interests include the molecular, cellular and physiological mechanisms regulating growth and metabolism.