Honours Projects 2020

Nature is full of remarkable nanoscale machines that can walk, talk, bind and self-assemble. As synthetic chemists, we have the opportunity to borrow from nature’s vast catalogue of biomolecules, and modify their properties to create synthetic macromolecules that can perform completely new functions – cancer drugs, smart materials and nanostructured catalysts.

Our research projects are very diverse! You can choose from projects that cover a wide range of techniques: organic synthesis, protein engineering, DNA design, microscopy, cell culture, biophysical assays, and peptide chemistry.

We also have co-supervised joint projects!

Flagship projects

Self-assembling protein cages for next-generation catalysis

Nature is a master of self-assembly, constructing functional nanoscale architectures from simple protein building blocks. Using synthetic chemistry, we can harness the power of self-assembling proteins to create new catalytic architectures.

This project involves chemical modification of encapsulins, bacterial proteins that spontaneously assemble into hollow ~30 nm shells (see Nat. Commun. 2018, 9, 1311). We will create nanoscale reaction vessels by functionalising the interior of these shells with enzymes and synthetic catalysts.

This project is in collaboration with A/Prof. Stephen Bell (University of Adelaide).

Anti-cancer peptide therapeutics

Macrocyclic peptide-based compounds are highly-underexploited molecule in drug development. Peptidic macrocycles can have exquisite selectivity and potency similar to protein drugs, and pharmacokinetics that are normally associated with small molecules.

In this project, we will establish a new strategy for synthesising vast libraries of macrocyclic ‘stapled’ peptides, using a combination of bioorthogonal chemistry and recombinant technologies (see Angew. Chem. Int. Ed. 2015, 54, 15410-15413). The resulting compound library will then be screened in cellular and in vitro assays to identify new anti-cancer drug candidates.

This project is in collaboration with Prof. Hilda Pickett (Children's Medical Research Institute, Westmead Hospital).

Building synthetic life: engineering artificial cellular compartments

Life is defined by compartmentalisation. All living things build compartments, each with a unique environment for hosting different chemical reactions.

In this project, we will create synthetic modified versions of the encapsulin family of self-assembling proteins (see Nat. Commun. 2018, 9, 1311) to create compartments with unique chemical properties within their interior. The ultimate goal is to generate new living organisms that possess artificial organelles with programmable chemical functions that are new to nature.

This project is in collaboration with Dr Tobias Giessen (University of Michigan, USA).

Secondary projects

New biocompatible reactions for protein modification

Site-specific modification of proteins is a major challenge for synthetic chemists. This is a question of chemoselectivity: how can we perform a reaction at a chosen functional group, without affecting the hundred other unprotected groups that exist on a protein?

In this project, we will develop new organic chemical reagents that only react with a chosen function group in a specific amino acid sequence. The project will involve reagent synthesis and screening for reactivity against different peptide sequences. These reagents will enable us to label proteins in cells to study their roles in disease, synthesise antibody-drug conjugates with improved efficacy.

Anion-binding gates for biomolecular cages (with Prof. Kate Jolliffe)

The Jolliffe group are experts at designing molecular receptors that can bind anions in aqueous media with high selectivity and affinity.

In this project, we will use anion-binding to control the porosity of self-assembled protein cages. The binding and unbinding of an anion to a receptor is analogous to a gate, which controls access to a fenced-off area upon opening and closing. By binding anions at the pores of our protein cages, we will control the ability of small molecules to enter and exit these cages, enabling new forms of selective catalysis and drug delivery.

Bio-templated inorganic and polymeric nanomaterials (with Dr Markus Muellner)

Nature can produce self-assembled 3D structures that are incredibly uniform and precise, beyond what is possible using conventional synthetic techniques.

In this project, we will create new inorganic and polymeric nanoparticles that are template by encapsulins: bacterial proteins that spontaneously assemble into hollow ~30 nm shells. By using biology to fabricate highly uniform nanoparticles, we can create high-value materials with completely new structural and catalytic properties.