Discovery and Characterisation of Novel NRF2 Activators

About the research project

Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of cellular defence against many different types of stress. Activation of NRF2 promotes the expression of cytoprotective genes involved in antioxidant defence, detoxification, DNA repair, and cellular survival. Consequently, NRF2 is an attractive therapeutic target for diseases associated with oxidative stress, DNA damage, xenobiotic stress and inflammation. However, currently available NRF2 activators are limited by poor selectivity, off-target effects and potential toxicity, which highlights the need to identify safer and more effective NRF2 activators.

Cannabidiol (CBD) has demonstrated antioxidant, anti-inflammatory and cytoprotective activities, with some evidence that these effects involve NRF2. Chemical modifications of CBD might therefore produce novel compounds with enhanced NRF2 activation and improved drug-like properties. Preliminary screening of a library of novel CBD analogues (synthesised in-house, Chemistry, School of Natural Sciences, University of Tasmania, Hobart, TAS, Australia) identified compounds that share particular and interesting structural features and strongly activate NRF2-dependent transcription with minimal or no detectable cellular toxicity. Our results point to a relationship between chemical structure and NRF2 activity and provide a strong foundation for further characterisation and drug development. With promising NRF2-active compounds already identified, the project is well positioned for further mechanistic investigation, optimisation and therapeutic development.

This project aims to identify novel CBD-based compounds that activate NRF2 and characterise their potential as therapeutic agents. The PhD candidate will investigate the biological activity of selected compounds and establish structure–activity relationships to determine how specific structural features and chemical modifications influence NRF2 activation. These findings will guide further chemical modifications by the Chemistry team to enhance their NRF2-activating activity and drug development potential. Promising compounds will undergo further assessment to establish their safety and pharmaceutical properties. This will include comprehensive in vitro toxicity profiling and the determination of their chemical and metabolic stability. A range of cellular, molecular and analytical techniques will be employed throughout the project, with the experimental approach refined as promising drug candidates are identified.

By integrating structure–activity relationships, biological activity, toxicity and stability, this project aims to identify the most promising CBD analogues for further development. The research will provide insight into the chemical features that drive NRF2 activation and support the rational selection and future optimisation of lead compounds.

Primary supervisor

Meet Doctor Mohammed Sedeeq

Funding

Applicants will be considered for a Research Training Program (RTP) scholarship or Tasmania Graduate Research Scholarship (TGRS) which, if successful, provides:

• a living allowance stipend funded by University of Tasmania of $34,315 per annum for 3.5 years
• a relocation allowance of up to $2,000
• a tuition fees offset covering the cost of tuition fees for up to four years (domestic applicants only)

A tuition fee offset may be offered to eligible international applicants following competitive assessment 

As part of the application process you may indicate if you do not wish to be considered for scholarship funding.

Additional Funding

This project will benefit from an existing collaboration with Martha Jane Medical (MJM) through the funded Novel Cannabinoids as Therapeutics project. This collaboration supports ongoing research at the University of Tasmania involving the design, synthesis and biological evaluation of novel cannabinoid-derived compounds as potential therapeutics. The proposed project will also provide a foundation for future collaborative grant applications to support further development and translation of this research.

Other funding opportunities and fees

For further information regarding other scholarships on offer, and the various fees for undertaking a research degree, please visit our Scholarships and fees on research degrees page.

Eligibility

Applicants should review the Higher Degree by Research minimum entry requirements.

Ensure your eligibility for the scholarship round by referring to our Key Dates.

Additional eligibility criteria specific to this project/scholarship:

• A Bachelor’s or Master’s degree in pharmacy, pharmaceutical science, pharmacology, biomedical science, biochemistry, molecular biology, or a related discipline, with a significant research component.

Selection criteria

The project is competitively assessed and awarded. Selection is based on academic merit and suitability to the project as determined by the College.

Additional essential selection criteria specific to this project:

• A degree with a significant research component, such as a Research Master’s degree, a Master’s degree with a substantial thesis component, or a Bachelor’s degree with First-Class Honours.
• Demonstration of experience in experimental research, including the ability to design, conduct, analyse, and interpret laboratory experiments.
• Demonstration of an understanding of statistical methods relevant to experimental data analysis and proficiency in using appropriate data analysis software.
• Demonstration of strong scientific writing and communication skills through a research thesis, scientific report, publication, conference presentation, or equivalent research output.
• Demonstration of the ability to work independently and collaboratively within a multidisciplinary research team, with good organisational and time-management skills.

Additional desirable selection criteria specific to this project:

• Experience in the following areas would be advantageous: mammalian cell culture, cell-based assays, molecular biology techniques, pharmacology, drug discovery, toxicological assessment, or pharmaceutical/chemical stability studies.

Application process

1. Select your project, and check that you meet the eligibility and selection criteria, including citizenship;
2. Contact Doctor Mohammed Sedeeq to discuss your suitability and the project's requirements; and
3. In your application:
   • Copy and paste the title of the project from this advertisement into your application. If you don’t correctly do this your application may be rejected.
   • Submit a signed supervisory support form, a CV including contact details of 2 referees and your project research proposal.
4. Apply prior to 1 October 2026.

Full details of the application process can be found under the ' How to apply ' section of the Research Degrees website.

Following the closing date applications will be assessed within the College. Applicants should expect to receive notification of the outcome by email by the advertised outcome date.

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