Kavli Research & Enterprise Discussions (K.R.E.D)
Kavli Research & Enterprise Discussions (K.R.E.D)
BIOCHEMICAL SOCIETY AWARD LECTURE
Date: 03 April 2025
Time: 11:00 - 17:40
Room: DCHB – Seminar Room 1
This is an event for University staff only.
Hosted by Professor Dame Carol Robinson and Professor Simon Newstead
In person event – seating is limited
Renae Ryan's Talk is entitled “The Twisted Link Between a Dual Function Glutamate Transporter and Episodic Ataxia”
Her abstract and biography are below.
Abstract:
Excitatory Amino Acid Transporters (EAATs) regulate excitatory neurotransmission by transporting glutamate into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs also conduct chloride ions (Cl-) via a channel-like process that is thermodynamically uncoupled from transport. The molecular mechanisms that allow these dual-function transporters to carry out two seemingly contradictory roles, and the physiological role of Cl- conductance of the EAATs, are not clear. I will describe the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, revealing an aqueous-accessible Cl- permeation pathway that is formed during the transport cycle and discuss the impact of a series of mutations in EAAT1 that have been identified in patients with the neurological disease episodic ataxia type 6 (EA6). By studying EAAT1 function and using a Drosophila melanogaster model of locomotor behaviour, our results indicate that mutations that lead to functional glutamate transport but either increased OR decreased Cl- channel activity contribute to the pathology of EA6, highlighting the importance of Cl- homeostasis in glial cells for proper central nervous system function. Our findings provide insight into the mechanism by which glutamate transporters support their dual functions and provides a framework for the rational development of therapeutics that can differentially modulate substrate transport or channel properties for the treatment of neurological disorders caused by EAAT dysfunction, such as Episodic Ataxia.
Biography:
Renae Ryan is a Professor of Biochemical Pharmacology at the University of Sydney, Australia. She received her PhD from the University of Sydney in 2004 and completed postdoctoral work with at Columbia University and the National Institutes of Health. Renae returned to the University of Sydney in 2007 where she leads a research team that investigates the molecular mechanisms of neurotransmitter and amino acid transporters and their role in cancer and neurological diseases, such as episodic ataxia. She has received several awards for scientific excellence, mentoring and outreach including the Nancy Millis Medal from the Australian Academy of Science and the Australian Museum Eureka Prize for Mentoring of Young Researchers. Renae is a globally respected leader and advocate for gender equity, diversity and inclusion, and a sought-after supervisor, mentor, and role model for women in science.
Agenda for the Day: Sessions & Discussions
Biochemical Society’s Winner of the International Award: Professor Renae Ryan, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Australia
“The twisted link between a dual function glutamate transporter and Episodic Ataxia”
Dr Jo Parker (Department of Biochemistry, Oxford)
“Developing novel strategies to target pathogenic fungi”
Professor Yimon Aye (Department of Chemistry, Oxford)
“Spatiofunctional maps of reactive immunometabolite responsivity in living systems"
Professor Balyn Zaro (University of California, San Francisco)
“You are what you eat: the consequence of phagocytosis at the macrophage cell surface”
Assistant Professor Nick Riley (University of Washington)
"Tools to explore complex glycoproteomics data"
Dr Ben Schumann (The Francis Crick Institute, London)
“Chemical Precision Tools to Dissect Protein Glycosylation”
