We are seeking a well-qualified and highly motivated candidate for the position of a doctoral student to carry out a peptide-based drug-design project involving a multi-disciplinary approach. The project targets the interaction between endoplasmic reticulum (ER) chaperone ERp44 and the collagenous hormone adiponectin. Adiponectin, abundantly and exclusively secreted from adipocytes (fat cells), exerts a wide range of beneficial functions against obesity-associated pathologies and is a potent biotherapeutic. In the ER, ERp44 tightly regulates oligomerization of trimeric adiponectin subunits that are responsible for its insulin-sensitizing and anti-inflammatory properties. Under obesity-induced ER stress, expression of ERp44 is dysregulated resulting in part to sequestration of adiponectin in ER. The concomitant reduction in serum-circulating level of adiponectin can lead to insulin resistance and type2 diabetes. We are exploring the action of rationally designed peptides that may interfere in ERp44-adiponectin interaction to release aberrantly trapped adiponectin as a means of mitigating the onset of metabolic syndrome in obesity.
The interdisciplinary project combines rationally designed peptide synthesis, biophysical characterization of the binding of these peptides with ERp44, including X-ray crystallography, and examination of their action in cellulo and in vivo towards elevating the level of circulating adiponectin. A 3-year funding from the Health Research Council of New Zealand supports this project. The candidate should have a background in one or more of the following disciplines: Structural Biology, biophysics, protein biochemistry, peptide synthesis.
The peptide synthesis will be carried out in an in-house state-of-the-art facility. The biophysical instrumentation suite includes ITC, DLS, Mass Spectrometry, NMR and CD. We have a modern in-house X-ray suite including two Mar detectors, cryo system and a crystallization robot. We also have direct access to the Australian Synchrotron facility.
- Radjainia, M, Wang, Y and Mitra, AK. Structural polymorphism of oligomeric adiponectin visualized by electron microscopy. J Mol Biol, 2008. 381(2): 419-30.
- Radjainia, M, Huang, B, Bai, B, Schmitz, M, Yang, SH, Harris, PW, Griffin, MD, Brimble, M A, Wang, Y and Mitra, AK. A highly conserved tryptophan in the N-terminal variable domain regulates disulfide bond formation and oligomeric assembly of adiponectin. FEBS J, 2012. 279(14):2495-507.
- Harris PW, Hampe L, Radjainia M, Brimble MA, Mitra AK. An investigation of the role of the adiponectin variable domain on the stability of the collagen-like domain. Biopolymers. 2014 Jul;102(4):313-214.
- Hampe, H, Radjainia, M, Xu, C, Harris, PWR, Bashiri, G, Goldstone, DC, Brimble, MA, Wang, Y, Mitra, AK. Regulation and Quality Control of Adiponectin Assembly by Endoplasmic Reticulum Chaperone ERp44. Journal of Biological Chemistry 2015. 290: 18111-1812.
- Hampe L, Xu C, Harris PWR, Chen J, Liu M, Middleditch M, Radjainia M, Wang Y, Mitra AK. Synthetic peptides designed to modulate adiponectin assembly improve obesity-related metabolic disorders. Br J Pharmacol. 2017 Sep 25. doi: 10.1111/bph.14050.
For further information, please send a current CV and contact Dr. Alok K. Mitra, School of Biological Sciences, University of Auckland, Auckland, New Zealand. Tel: +64 09 923 8162, E.mail: firstname.lastname@example.org