12.00 – 1.00 pm
Level 3 Seminar Room
15 Innovation Walk
Clayton campus
Dyslipidaemia is a common feature of Western society and can manifest itself as elevated plasma LDL cholesterol levels. The E3 ubiquitin ligase, IDOL, is a novel regulator of LDLR-dependent cholesterol uptake. We identified critical residues within IDOL that bind a newly identified recognition sequence in the cytoplasmic tails of its lipoprotein receptor targets, LDLR, VLDLR and
ApoER2. We also identified a SNP within the FERM domain of
IDOL that is associated with increased plasma cholesterol in humans. Finally, we demonstrated that IDOL controls its own stability through autoubiquitination and mutation of key residues generated a molecule resistant to autodegradation but with intact
E3 ligase activity, termed “super IDOL”. Transgenic expression of sIDOL in the liver resulted in a hypercholesterolaemia and a concomitant increase in atherosclerosis..
Dr Anna Calkin
PhD
Baker IDI Heart & Diabetes Institute
Dr Anna Calkin completed her PhD studies at BakerIDI before undertaking postdoctoral training at the Australian Centre for Blood
Diseases as a NHMRC Peter Doherty Fellow. She demonstrated that rHDL mediated powerful anti-thrombotic properties in humans.
An NHF Overseas Fellowship took Anna to UCLA for 4 years under the mentorship of Peter Tontonoz where she worked on a novel pathway that regulates LDL cholesterol, IDOL. Her work identified the functional mechanism of the IDOL-LDLR interaction and its importance in humans. She also developed a pre-clinical model of atherosclerosis, which has been licensed to Astra Zeneca and deposited with JAX. Anna returned to Baker IDI in 2013 to lead the
Diabetes and Dyslipidaemia Group. A NHF Future Leader Fellow, her work aims to prevent the damage caused by excess cholesterol and triglycerides that promote the onset of diabetes and cardiovascular disease as well as identify novel regulators of lipid metabolism. Anna has funding from the NHMRC, NHF and CASS
Foundation..
www.monash.edu/discovery-institute
CRICOS Provider: Monash University 00008C.