ATP is a critical energy-carrying molecule that fuels processes inside cells, making it essential for cellular function. However, until recently, there have been limited methods for tracking ATP levels in living cells. Previous sensors were ineffective due to being dim, slow, or difficult to use. In 2019, researchers at Janelia and UCLA developed the iATPSnFR fluorescent protein sensor, which could detect changes in ATP but only operated within a narrow range.
Now, a new and improved sensor, iATPSnFR2, has been developed by Janelia scientists and collaborators, led by Jonathan Marvin. This next-generation sensor has the capability to track ATP concentrations over a much broader range, allowing researchers to study ATP levels inside living cells in greater detail than ever before. This advancement enables scientists to gain a better understanding of how fluctuations in cellular ATP levels impact cell function and contribute to disease.
Tim Ryan, a researcher at Weill Cornell Medicine and a Janelia Scholar, has utilized the iATPSnFR2 sensor to track changes in ATP at individual synapses, where neurons communicate. By observing these changes directly, Ryan and his team are investigating how alterations in ATP activity at synapses could be linked to the development of Parkinson’s disease. This new sensor provides them with a powerful tool to study these processes and shed light on the role of ATP in disease progression.
The development of the iATPSnFR2 sensor not only enhances the ability to study ATP in the context of specific diseases, but it also opens up new possibilities for investigating a wide range of research questions related to ATP. With its increased range and sensitivity, this sensor can be used by other scientists to explore various aspects of ATP biology that were previously challenging to study with existing tools.
The sensor works by attaching a fluorescent molecule to a protein that binds ATP. When ATP binds to the protein, causing it to change shape, the fluorescent molecule lights up, providing researchers with a visual signal of ATP levels. This real-time monitoring of ATP concentrations inside living cells offers invaluable insights into the dynamic nature of cellular energy metabolism and its impact on cellular functions.
By enabling the direct observation of ATP fluctuations in living cells, the iATPSnFR2 sensor represents a significant advancement in the study of cellular energy metabolism. Its broad range and enhanced sensitivity make it a valuable tool for researchers investigating the role of ATP in normal cellular function and disease processes. This innovation has the potential to deepen our understanding of ATP biology and its implications for various cellular processes, opening up new avenues for research in cell biology and biomedical sciences.