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Calixarene-controlled Protein Assembly & Crystallization

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  • Full or part time
    Prof Peter Crowley
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The Crowley laboratory specializes in protein assembly, with a focus on structural characterization. We are recruiting a PhD candidate to begin in September 2019.

Controlled protein assembly provides a means to construct biocompatible, nanoscale devices and functional materials. Porous assemblies are particularly attractive considering their applications in storage, delivery and catalysis. Protein architectures including nanocages have been generated from self-assembling building blocks with engineered interfaces. Crystalline architectures, characterized by highly-ordered 3D arrays and in some cases nanoscale porosity, are also well-studied. Ligands that facilitate protein assembly and crystallization have emerged as game-changers in the development of protein frameworks. Such “molecular glues” trigger assembly by providing a surface on which two or more proteins can associate. Importantly, the choice of glue can yield different protein architectures.

Macrocycles such as calixarenes and cucurbiturils are versatile "glues" for protein assembly and crystallization.[1-4] We have shown how sulfonato-calix[8]arene can control the assembly of lysine-rich cytochrome c.[3] Interestingly, different types of assemblies were generated depending on the protein – calixarene ratio. While our work to date has focused on cationic proteins[1,4] now we will expand the scope to include neutral proteins. Our main interest is to discover methods of generating porous assemblies with potential applications in sensing and catalysis.

We are looking for a highly motivated PhD candidate with a passion for protein science. Applications are welcome from BSc or MSc graduates of Chemistry, Biochemistry or Biotechnology. Prior experience in protein purification is an advantage.

Applications to include:
- motivation statement (~500 words)
- 2 page CV
- contact details for 2 referees
- PDF of BSc or MSc thesis

Start date - September 2019.

Informal enquiries to [Email Address Removed]

Funding Notes

This four year fully-funded project is part of SFI research centre SSPC-Pharm5, and includes an annual stipend (€18,500), registration fees, consumables costs and travel allowance.

References

1.
McGovern RE, Fernandes H, Khan AR, Power NP, Crowley PB
Protein camouflage in cytochrome c - calixarene complexes.
Nature Chem. 2012, 4, 527-533.

2.
Guagnini F, Antonik PM, Rennie ML, O'Byrne P, Khan AR, Pinalli R, Dalcanale E, Crowley PB Cucurbit[7]uril-dimethyllysine recognition in a model protein.
Angew. Chem. Int. Ed. Engl. 2018, 57, 7126-7130.

3.
Rennie ML, Fox GC, Pérez J, Crowley PB
Auto-regulated protein assembly on a supramolecular scaffold.
Angew. Chem. Int. Ed. Engl. 2018, 57, 13764-13769.

4.
Alex JM, Rennie ML, Engilberge S, Lehoczki G, Dorottya H, Fizil Á, Batta G, Crowley PB
Calixarene-mediated assembly of a small antifungal protein.
IUCrJ 2019, 6, 238–247.



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