Wellington, New Zealand | Contact Jasmine
Bacterial nitroreductases for cancer therapy
Bacterial-directed enzyme prodrug therapy (BDEPT) employs tumour-tropic bacteria armed with a payload of enzymes, such as nitroreductases, that activate a conditionally toxic prodrug inside of tumours. My research aims to engineer superior nitroreductases, using directed evolution, that can efficiently activate nitroaromatic prodrugs to a genotoxic form that can kill cancer. By engineering superior activating enzymes we can make this targeted cancer therapy even more effective.
I was born and raised in Wellington. I have been a planetarium presenter, at Space Place at the Carter Observatory, for the last six years through which I have gained experience in science communication and science theatre. I have been a long-term volunteer and supporter of Chiasma Wellington - a student organization that connects science students to science industry and ministry in NZ. I am comfortable at the lab bench, behind a microphone communicating science to public or academic audiences and I enjoy creating professional science illustrations.
Southland, New Zealand | Contact Kelsi
Directed evolution of bacterial nitroreductases for improved prodrug activation.
My project involves simultaneous randomisation of key active site residues in the E. coli nitroreductase, NfsA, to generate a library containing 430 unique variants. I am using this library to identify superior nitroreductases for prodrug activation. A primary focus has been developing these nitroreductases as tools for targeted cell ablation in zebrafish to create disease models.
Hamilton, New Zealand | Contact Abby
Engineering of nitroreductase enzymes for improved activation of prodrugs and imaging molecules
Bacterial nitroreductase enzymes are proving important tools in the development of new cancer therapies and also in ablation studies that aim to elucidate mechanisms of tissue regeneration. When localised to and expressed in a cell, a nitroreductase enzyme can ‘flick a molecular switch’, reducing otherwise innocuous prodrugs to cytotoxic forms that induce cell death in a targeted manner. An additional, very useful property of nitroreductase enzymes is their ability to activate nitro-masked fluorophores or positron emission tomography (PET) imaging probes. Non-invasive fluorescent or PET imaging enables visualisation of the cells or tissues in which the enzyme is being expressed, allowing one to confirm localisation before delivering the prodrug and inducing cell death. This project aims to use directed evolution to engineer superior nitroreductase enzymes for use in targeted cellular ablation studies for the development of degenerative disease models in zebrafish, and in the development of gene-directed enzyme prodrug therapies for cancer treatment.
Christchurch, New Zealand | Contact Jack
Engineering and Characterisation of Bacterial Phosphopantetheinyl Transferases and their Peptide Substrates.
The phosphopantetheinyl tranferases (PPTases) comprise a class of enzymes that is important in both primary and secondary metabolism throughout all domains of life. Their primary function is to attach a chemical moiety from coenzyme A to other proteins, an activity that has great biotechnological potential, particularly in protein tethering, site-specific labelling, hydrogel formation, and others. In addition to the characterisation of these enzymes, my work aims to re-purpose these enzymes by altering their substrate specificity via directed evolution.