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Better together: constructing engineered protein oligomers using synthetic biology

   Cardiff School of Biosciences

About the Project

One of the most important events a protein will undergo is associating with itself or other proteins to from a functional complex; this is known as oligomerisation. Protein oligomerisation is common in nature, with the majority of cellular proteins existing either permanently or transiently as oligomers. Oligomerisation is normally cooperative and synergistic in that properties such as function and stability are greatly enhanced compared to the monomeric form, and new properties can emerge (e.g. functional enhancement, switching); there is normally communication between individual monomer units that leads to these new or enhanced properties.

Your PhD research project will involve taking normally monomeric proteins and then designing, building, and testing new oligomeric protein species.

While oligomerisation could be considered desirable, it is difficult to engineer into functional monomeric proteins due to the complexity of natural protein-protein interfaces. To meet this challenge, you will use a new combined computational and synthetic biology approach recently developed in the Jones group for generating protein oligomers. As part of the project, you will link proteins using their inherent chemistry and introducing new chemistry not found in nature. For the latter, you will use a reprogrammed genetic code to incorporate non-natural amino acids (nnAA) at designated residues in a target protein. At least two different types of nnAA will be used that react in a 1 to 1 basis to form a defined crosslink. Using this approach, you will explore the construction of dimer, trimers and beyond composed of identical and mixed protein units to generate a myriad of new structures of potential fundamental and technological use. Your project will initially focus on autofluorescent proteins but will quickly move on to constructing multi-enzyme complexes. This interdisciplinary project will focus on protein design and engineering but will also expose you to elements of chemistry and biophysics. 

Techniques: computational analysis, molecular biology (cloning and mutagenesis), synthetic biology (reprogrammed genetic code systems), protein chemistry (purification and analysis), protein 3D structure determination, biophysical analysis (various spectroscopy methods, including single molecule analysis).

The project will suit a person with a background/degree in biochemistry/chemical biology or those with a degree in chemistry willing to learn biochemistry.

For more information contact Dr Dafydd Jones ().

How to apply

To submit a formal application via Cardiff University’s online application service, click the 'Institution Website' button on this advert; in the ‘Apply’ box at the top-right of the page, select Qualification (Doctor of Philosophy), Mode of Study (Full Time) and Start Date (this can be flexible as it is a self-funded project). This will take you to the application portal.

Candidates must submit the following:

 • Supporting statement

 • CV

 • Qualification certificates

 • Proof of English language (if applicable) 

In the research proposal section of the application, specify the project title and supervisors of the project. In the funding section, specify that you will be self-funding. If you are applying for more than one Cardiff University project with the same entry intake, please note this in the research proposal section as the form only allows you to enter one title.

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