Platform technology unlocks new therapeutic targets

Researchers from the University of Adelaide have developed a new technology for drug and functional genomics screenings, which could reshape the way diseases are treated. 

The technology called dFLASH (dual FLuorescent transcription factor Activity Sensor for Histone-integrated live-cell reporting) is a modular biological pathway sensor which enables identification of new cellular targets in the treatment of disease.  

dFLASH’s overall goal is to develop a system that would enable researchers to investigate any pathway of interest in cells to explore how they could be targeted in the treatment of disease and/or used to develop new medicines.  

This new technology enables rapid screening of hundreds of thousands to millions of individual drugs or genes in living cells to accelerate the identification of new therapeutic targets and medicines.  

The work by researchers across the University's School of Biological Sciences, Robinson Research Institute (RRI), Adelaide Centre for Epigenetics, South Australian immunoGENomics Cancer Institute (SAiGENCI) has been published in Nature Communications. 

To demonstrate this, the authors used dFLASH to explore how cells respond to low oxygen, which is very important in the treatment of cancer and anaemia, and the hormonal progesterone signalling pathway which plays imperative roles in controlling female reproduction.  

Together, dFLASH provides a highly sensitive system which can be used for large scale drug and genetic based screens, to identify new drugs and genes (DNA) that control signalling pathways of therapeutic interest. 

"Live-cell transcription factor (TF) activity reporting is crucial for synthetic biology, drug discovery and functional genomics," said senior author and grant-funded researcher Dr David Bersten from RRI. 

"This significantly accelerates the discovery of potential treatments across a range of conditions, including cancer, metabolic disease, and non-hormonal contraceptive candidates 

"It opens the door to faster, more cost-effective identification of new drug targets.” 

Paper co-author and Higher Degree by Research candidate Alison Roennfeldt said the dFLASH was already powering several exciting new directions. 

"We’re now using it to enable precision targeting for cellular therapies and to explore the regulatory grammar of DNA - how the sequence and structure of DNA affect gene control," said Ms Roennfeldt, also from RRI. 

"These advances could reshape the way we approach disease treatment and genetic research." 

Dr Bersten said the research highlights the power of collaborative innovation in driving forward next-generation tools for biology and medicine, with the School of Biological Science labs of Professor Murray Whitelaw, Associate Professor Daniel Peet and Professor Darryl Russell all collaborating in this project. 

"We believe dFLASH will serve as a foundational technology for both academic research and therapeutic development, with broad applications across biomedical science," Dr Bersten aid.