Rational design and synthesis of novel pharmacological chaperones to treat Krabbe disease
Chaperone-mediated therapy (CMT) is an exciting new strategy to rescue partially-defective enzymes using small molecules called pharmacological chaperones (PCs). A PC selectively binds to the active site of the mutated enzyme, facilitating the restoration of enzyme function. CMT can treat devastating orphan disorders but its uptake/utilization is limited by the design and synthesis of PCs.
This project is designed to maximize the chance of developing successful PCs by using enzymatic transition-state analysis. This powerful technique effectively provides a blueprint for the design of PCs by describing enzyme transition-state features. We will apply this technique to β-galactosylcerebrosidase, the enzyme involved in Krabbe disease, a fatal neurodegenerative disorder. The second part of this project will involve the design, synthesis, and testing of potential PCs.
This is a cross-disciplinary project involving elements of synthetic organic chemistry, analytical chemistry, and biochemistry. In this project, you will gain experience in chemical and enzymatic synthesis of small molecules and become proficient using the associated characterization techniques (LC-MS, NMR etc). If interested, you could also be involved in the expression and purification of required enzymes. This project will thus allow you to master a broad range of skills.
Prospective applicants should apply to Dr. Farah Lamiable-Oulaidi at firstname.lastname@example.org. The Stipend is $27,500 pa and full fees will be paid.
It is essential that the successful applicant has a strong background in organic chemistry, and preferably also biochemistry or bioorganic chemistry. Applicants will have a BSc (Hons), MSc or equivalent degree in chemistry or biochemistry with a focus on organic chemistry. Applicants also must meet the Victoria University of Wellington English language requirement.
When applying please ensure all required documents are attached:
• All degree certificates and transcripts (Undergraduate AND Postgraduate MSc-officially translated into English where necessary)
• Detailed CV
• Details of 2 academic referees
• Statement of research interests