Project Description
The binding of cell-surface carbohydrates to carbohydrate binding proteins mediates a wide range of physiological and pathophysiological processes including embryogenesis, protein folding and trafficking, immune regulation and inflammation[1], microbial infection[2] and cancer.[3] These fundamental cell-cell and cell-matrix binding events are also associated with microbial infection and cancer progression. This has promoted significant effort toward the development of synthetic carbohydrate receptors as biological probes and drug leads for the treatment of HIV and cancer.[4-6] However, the rational design and synthesis of synthetic carbohydrate receptors de novo poses numerous biochemical and synthetic challenges. This project will utilize a new paradigm for the synthesis and screening of synthetic carbohydrate receptors, or “synthetic lectins”, based on principles of reversibility, molecular recognition and adaption. Dynamic combinatorial libraries of cyclic peptides and glycopeptides will be synthesized and screened in situ as receptors for carbohydrates implicated in disease related processes.
The PhD scholarship will be supported by the Australian Research Council (DECRA project) project entitled “Access to Biomimetic carbohydrate receptors using dynamic combinatorial chemistry”. A successful PhD student will be supervised by Dr Brendan Wilkinson (Monash University) and will work closely with international and local collaborators throughout the course of the project. The project will combine areas of organic synthesis, analytical chemistry and glycobiology for the development of biomimetic carbohydrate receptors, or “synthetic lectins”. The outcomes of this project will establish new structure-activity relationships with respect to the specificity and affinity of some poorly understood lectins, and help identify potential drug leads for the treatment of various cancers and microbial infection. The project will largely be conducted at the School of Chemistry, Monash University. The candidate will also be heavily involved in the biological screening and lectin array assays for synthesised receptors, which will be conducted at the Burnet Institute (Melbourne) and the Institute for Glycomics at Griffith University, respectively.
Interested candidates should directly contact Dr Brendan Wilkinson by e-mail: [Email Address Removed]
Funding Notes
International applicants must apply through the faculty of science for a stipend valued at 25,000 AUD per annum AND a scholarship to cover tuition fees. These scholarships are very competitive. Only applicants with a recent IELTS/TOEFL score, strong academic performance, peer-reviewed publication(s) (desirable, not essential) and letters of recommendation will be considered.
References
References
1. Almkvist, J.; Karlsson, A. Glycoconjugate J. 2004, 19, 575-581
2. Hooper, L. V.; Gordon, J. I. Glycobiology 2001, 11, 1R-10R.
3. Barrow, H.; Rhodes, J. M. Int. J. Cancer 2011, 129, 1-8.
4. Thijssen, V. L.; Poirier, F.; Baum, L. G.; Griffioen, A. W. Blood 2008, 110, 2819-2827.
5. Sookcharoenpinyo, B.; Klein, E.; Ferrand, Y.; Walker, D. B.; Brotherhood, P. R.; Ke, C.; Crump, M. P.; Davis, A. P. Angew. Chem. Int. Ed. 2012, 51, 4586-4590.
6. Balzarini, J. Antivir. Chem. Chemother. 2007, 18, 1-11.
