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“The trafficking and storage of cellular lipids: from fundamental biology to new therapies against cancer and diabetes.”

School of Medical Sciences Seminar Series

Speaker: Professor Rob Yang, School of Biotechnology and Biomolecular Sciences (BaBS), UNSW Sydney

Bio:

Dr. Hongyuan (Robert) Yang is currently a professor at BaBS. He obtained a Bachelor of Medicine degree from Peking University Health Science Center (Beijing, China) in 1993; and a Ph.D. from Columbia University College of Physicians and Surgeons (New York, USA) in 1998. He was an inaugural ARC Future Fellow (2010-2013) and an NHMRC Senior Research Fellow (2014-2019). His research focuses on the trafficking and storage of lipids in eukaryotic cells and animals. His group identified seipin as a key regulator of the formation of lipid droplets. His work also unveiled new principles that govern the trafficking of lipids (e.g., cholesterol and phosphatidylserine) between cellular organelles. He has published more than 100 peer reviewed articles and book chapters, including many as a corresponding author in high impact journals such as Cell, Molecular Cell, Developmental Cell, J Cell Biol., Nature Comms, Diabetes and Cell Reports etc. His work is internationally recognized as he has been frequently invited to speak at top international conferences such as Gordon, FASEB, Keystone and Cold Spring Harbor Asia etc. He recently joined the editorial board of the Journal of Cell Biology, for which he is required to handle ~8 manuscripts/year.

Abstract:

Berardinelli-Seip Congenital Lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. In eukaryotic cells, seipin regulates the formation of lipid droplets (LDs). Exactly how seipin, an integral membrane protein of the endoplasmic reticulum, may regulate adipogenesis and LD biogenesis remains unclear. Our past genetic and biochemical data have linked seipin with phosphatidic acid (PA), a key intermediate for the synthesis of all glycerolipids. We recently resolved the partial structure of human seipin, which has a β-sandwich fold that can bind anionic phospholipids including PA. Moreover, our results in vitro and in vivo demonstrate that seipin functions to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs) to control the level of PA in the ER. Collectively, these data suggest that seipin functions to maintain phospholipid homeostasis of the ER, and that GPAT inhibitors may be used to treat BSCL2.

Cholesterol and phosphatidylserine are essential constituents of cellular organelles, but their distribution is highly uneven among cellular membranes: both are highly enriched in the plasma membrane. The oxysterol binding protein (OSBP) and OSBPrelated protein (ORPs), evolutionarily conserved lipid transfer proteins, may function to maintain membrane lipid distribution. We recently identified ORP2 as a cholesterol transfer protein that specifically delivers cholesterol to the plasma membrane from endosomal compartments. We also discovered that ORP5/8 can deliver phosphatidylserine from the ER to the plasma membrane and LDs. Both cholesterol and phosphatidylserine in the plasma membrane can promote cell proliferation. Our results suggest that some of the ORPs are novel therapeutic targets against cancer.

More info: Dr John Lock at john.lock@unsw.edu.au, Dr Nicola Smith at nicola.smith@unsw.edu.au,
Greta Spies at g.spies@unsw.edu.au

Event Date: 
Wednesday, 10 February 2021 - 3:00pm
Location: 
Online via Microsoft Teams Meeting
Open to: 
All
Event Type: 
Seminar
Booking deadline: