Newswise — Cells in our body are programmed to die after a certain period of time—a natural process known as apoptosis or “cell suicide.” This process is essential for maintaining the body’s balance. When aged or damaged cells are not properly eliminated, it can lead to diseases such as cancer, cardiovascular disorders, and dementia. Therefore, accurately observing when and how cells die has become a crucial tool in life sciences and medicine, particularly for early disease diagnosis and evaluation of therapeutic efficacy.
A research team led by Dr. Sun-Uk Kim at the Future Animal Resource Center of the Korea Research Institute of Bioscience and Biotechnology (KRIBB) has successfully developed a novel fluorescent reporter technology that enables real-time visualization of apoptosis inside living cells. By overcoming the limitations of conventional apoptosis detection methods, this breakthrough technology is expected to open new opportunities for drug discovery and biomedical research.
Until now, apoptosis detection has relied on methods such as microscopy observation, genetic analysis, and traditional fluorescent protein reporters. However, these methods often involved complex sample preparation, additional staining steps, and issues with accuracy.
The KRIBB team focused on caspase-3, a key enzyme that serves as the “final executioner” of apoptosis. Caspase-3 selectively cleaves a short amino acid sequence known as DEVDG. By precisely inserting this sequence into the structure of GFP (green fluorescent protein), the researchers engineered a biosensor that loses fluorescence at the moment apoptosis occurs. This “fluorescence switch-off” mechanism allows for real-time and highly sensitive detection of apoptosis.
Among the GFP-based reporters developed so far, KRIBB’s system stands out for its simplified operating principle and compact design, which greatly enhance both sensitivity and accuracy. The team further validated the sensor by tracking apoptosis in real time under various experimental conditions, including exposure to toxic substances and anticancer drugs.
Importantly, the new technology is applicable not only to cancer cell lines but also to a wide range of animal cell models, making it a powerful tool for evaluating drug-induced cytotoxicity and verifying therapeutic efficacy. Looking ahead, the fluorescent apoptosis reporter is expected to contribute significantly to studies on Alzheimer’s disease, cardiovascular disorders, and cancer, all of which are closely linked to programmed cell death.
Dr. Sun-Uk Kim, who led the study, emphasized
“Our newly developed sensor allows apoptosis to be monitored with greater sensitivity and simplicity than existing methods. We anticipate it will accelerate the evaluation of new drug candidates, such as anticancer agents, and serve as a powerful tool in studies of neurodegenerative diseases where cell death plays a pivotal role.”
Korea Research Institute of Bioscience and Biotechnology (KRIBB) is a leading national research institute in South Korea dedicated to cutting-edge research in biotechnology and life sciences. Established in 1985, KRIBB focuses on advancing scientific knowledge in areas such as molecular biology, genomics, bioinformatics, synthetic biology, and aging-related studies. As a government-funded institute, KRIBB plays a pivotal role in driving innovation, supporting national R&D strategies, and collaborating with academic and industrial partners both domestically and internationally.
This research was supported by Big Issue Group Program(KRIBB Research Initiative Program) and the Global TOP Program funded by the National Research Council of Science & Technology (NST), the Excellent Young Researcher Program under the Basic Science Research Program of the Ministry of Science and ICT (MSIT), and the Core Technology Development Program for the Bio-Industry of the Ministry of Trade, Industry and Energy (MOTIE).
The study was published online on June 24, 2025, in the prestigious international Journal of Advanced Research (Impact Factor: 13.0) under the title: “Designing an apoptosis reporter by mutagenesis-based insertion of caspase-3 cleavage motif into green fluorescent protein.”
(Corresponding Authors: [KRIBB] Drs. Sun-Uk Kim, Young-Ho Park)
(First Authors: [KRIBB] Drs. Dong Gil Lee, Hae-Jun Yang, Unbin Chae)