Developing Precision Medicines to Treat KCNT1 Epilepsy - a neurological disorder affecting children

About the project

Help combat childhood epilepsy 

If you are keen to pursue a career in the pharmacogenomics industry and motivated to make a difference in childhood epilepsy research, the University of South Australia – Australia’s University of Enterprise – is offering a hands-on project-based PhD with real-life impact within the Australian Centre for Precision Health (ACPreH), in partnership with the international foundation for patients with KCNT1 Epilepsy.

Our project aims to identify new drugs to treat a neurological disorder caused by mutations in the potassium channel gene KCNT1. Our research group discovered mutations in KCNT1 in individuals with neurological features, including seizures, intellectual disability and global developmental delay. 

Seizures usually begin in infancy and are followed by progressively worsening intellectual and physical abilities, often leading to premature death. Mutations in KCNT1 are gain of function, with increasing potassium currents and lead to seizures. 

With collaborators in structural biology and medicinal chemistry, we have used a 3D structure of the KCNT1 ion channel to screen a virtual library of FDA drugs to identify those that could bind and block the channel. 

We have been able to show that some drugs are able to block mutant KCNT1 channel in human cultured cells. We are now investigating the most promising candidates from the in vitro experiments for the ability to suppress KCNT1 seizures in our humanised Drosophila models. 

You will generate Drosophila models with KCNT1 patient mutations and use these models to test which candidate drugs suppress seizures for the different patient mutations. This pharmacogenomics approach will identify the best candidate drug for patients, based on their KCNT1 mutation. 

You will be based in ACPreH, working with distinguished and renowned researchers in their fields. Their expertise and mentorship will ensure that you thrive in your studies and make a valuable contribution to the project. You will have access to world-class facilities and resources and join a vibrant cohort of researchers who are focused on producing impactful outcomes from research. 

What you’ll do

In this project-based research degree, you will learn a range of scientific techniques, including molecular biology, animal behaviour seizure analysis and electrophysiology to analyse the seizure behaviour and efficacy of drugs in treating KCNT1 Epilepsy. 

You will also be involved in developing and implementing AI and machine learning-based object detection software to analyse the seizure behaviour of our Drosophila models. 

You will have the opportunity to present your work at various forums across the University and engage with other researchers working on cutting-edge projects. There are opportunities to engage with a wide range of stakeholders, including treating clinicians (both GPs and neurologists), patients, outreach organisations, chemical synthesis and pharmaceutical companies, and regulatory bodies.

Part of your work will form the largest mechanism-based pharmacogenomic analysis of a disease gene carried out to date and will be a landmark piece of work leading to high quality publications. This is a unique opportunity that will equip you with enviable experience, skills and professional connections. 

You may also have the opportunity to attend one international or domestic conference to present your work, which will be a great learning experience and expose you to the international research community.

Please note: as you will be dealing with living biological systems and model organisms, there will be a requirement to work outside of office hours in order to conduct experiments that align with the organism’s circadian rhythms.

Where you’ll be based

You will be based at the ACPreH, which is a research concentration that brings together a multidisciplinary group of leading experts in genomics, population health and evidence translation. 

Our vision is to keep people healthy by personalising health advice based on the differences in our genes and environment. We do this by discovering ways to improve risk prediction and risk factors, developing cutting edge methods for personalised prediction and prevention of diseases, and translating our findings into health education to help prevent the onset of disease. Financial Support

This project is funded for reasonable research expenses. Additionally, a living allowance scholarship of $35,200 per annum (2025 rate) is available to eligible applicants. Australian Aboriginal and/or Torres Strait Islander applicants will be eligible to receive an increased stipend rate of $50,291 per annum. A fee-offset or waiver for the standard term of the program is also included. For full terms and benefits of the scholarship please refer to our scholarship information for domestic students or international students.
 
Eligibility and Selection

This project is open to applications from both Domestic and International applicants. 

Applicants must meet the eligibility criteria for entrance into a PhD. Additionally, applicants must meet the project selection criteria:

•    Be highly self-motivated and goal oriented with a strong desire to contribute to cutting edge medical research
•    Knowledge (and ideally experience) in genetics, pharmacology, statistics, molecular biology
•    Understanding and knowledge of computer programming and coding languages such as Python

All applications that meet the eligibility and selection criteria will be considered for this project.

The successful applicant is expected to study full-time and to be based at our City East campus in the heart of Adelaide.

Essential Dates

Applicants are expected to start in a timely fashion upon receipt of an offer. Extended deferral periods are not available. Applications close on Wednesday 11 December 2024.