Development of a new class of ligase enzymes for protein engineering and drug development

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Supervisor – Dr Thomas

We have recently identified an enzyme-family that can efficiently catalyse cyclisation and ligation of a range of structurally and functionally diverse peptides and proteins. The favourable kinetics and short sequence requirements of these enzymes make them ideal candidates for development as a universal tool for efficient peptide and protein engineering, including production of peptide macrocycles or precision engineering of large protein conjugates of therapeutic value, such as antibody drug candidates or immunotoxins.

The project aims to further optimize these enzymes for biotechnological applications. Techniques employed will include molecular evolution, protein expression and purification, protein engineering and Xray crystallography. The enzymes will be used to create unique protein constructs of potential therapeutic value such as immunotoxins. Techniques used in this part will include protein chemistry and purification, mass spectrometry, cell culture, cell biology and microscopy and biochemical assay development.

This highly-multidisciplinary and collaborative PhD project will be well integrated into ongoing research at the Institute for Molecular Bioscience and the ARC Centre of Excellence for Innovations in Peptide and Protein Science .

Further reading:

  1. Harris, K. S, et al. Efficient backbone cyclization of linear peptides by a recombinant asparaginyl endopeptidase. Nat. Commun. 2015, 6, 10199.
  2. Rehm, F. B. H.; et al. Site-Specific Sequential Protein Labeling Catalyzed by a Single Recombinant Ligase. J. Am. Chem. Soc. 2019, 141, 17388-17393.
  3. Du, J. Q.; et al. A bifunctional asparaginyl endopeptidase efficiently catalyzes both cleavage and cyclization of cyclic trypsin inhibitors. Nat. Commun. 2020, 11, 1575.
  4. Rehm, F. B. H.; et al. Improved Asparaginyl-Ligase-Catalyzed Transpeptidation via Selective Nucleophile Quenching. Angew. Chem. Int. Ed. 202060, 4004-4008

Preferred educational background

Applications will be judged on a competitive basis taking into account the applicant's previous academic record, publication record, honours and awards, and employment history.

A working knowledge of molecular biology and protein expression and purification would be of benefit to someone working on this project.

The applicant will demonstrate academic achievement in the field(s) of biochemistry and the potential for scholastic success.

A background or knowledge of protein engineering is highly desirable.

*The successful candidate must commence by Research Quarter 1, 2022. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

Apply now