Published in PNAS, the first of its kind probe can rapidly trace tens of thousands of tagged proteins inside cells. With a response time within two minutes and at a quarter of the cost, the new fluorescent probe provides an inexpensive and effective tool for real-time monitoring of cell activities.
After three-year of efforts, Professor Sun Hongzhe of the Department of Chemistry and his team of researchers, together with his collaborators in the Faculty of Science and Faculty of Medicine, the University of Hong Kong, is the first to develop the novel fluorescent probe that can rapidly trace the tens of thousands of tagged proteins inside cells. The findings were published in the journal Proceedings of the National Academy of Sciences. This unprecedented strategy of designing fluorescent probes reported by Professor Sun's team has filed the patents from the US and Europe.
Scientists have been searching for ways to observe the location of tagged proteins within the cell and to understand how this changes with time as the cell performs different functions. The HKU research team led by Professor Sun provides quick labeling of tagged protein inside cells (in min) for observing the precise localisation of proteins for studying their functions in all types of cells, from bacterial cell to mammalian cells and even to highly complex plant tissues. The new fluorescent probe provides an inexpensive and effective tool for real-time monitoring of cell activities. It may be used to visualise the invasion events of pathogenic microbes and to analyse the actions of drug on its target, to assess the effectiveness of target drugs on cancer cells, and to trace and understand drug resistance in bacteria etc. It will facilitate drug screening for future drug discovery, in particular the development of more effective target drugs. The fluorescent probe may also be applied to agricultural advancements in developing plant species with favorable genetic variations.
Scientists frequently use genetic modification so that proteins of interest can be marked for purification and/or observation. One such tag, termed a hexahistidine-tag (His-tag), has been used for many years because it is simple and has minimal effect on perturbing the natural functioning of a protein of interest. Large libraries with tens of thousands of proteins each individually encoded with this small tag have thus been developed in recent years. The next question becomes -- can we observe where each of these proteins is within the cell and how this changes with time as the cell performs different functions?
To answer this question, Professor Sun's research team has developed a novel fluorescent probe to rapidly label intracellular tagged proteins (in min) with a reduction to only one-fourth of the cost of current methods. Scientists have spent tremendous efforts to monitor this class of proteins in living systems but Professor Sun's team is the first to have succeeded. Challenges include getting the probe across the cell membrane, ensuring the probe does not disturb the natural functions of the target proteins, and is not toxic to cells. After three-year of efforts, Professor Sun's team has created, up till now, the only small molecule-based fluorescent probe that can achieve this aim and will help us understand the functions of tens of thousands of proteins in all types of cells, from bacterial cell to mammalian cells and even to highly complex plant tissues. Furthermore, researchers in the group have also developed probes with different colors to enable the observation of the precise localization of multiple proteins within the same cells simultaneously, which is critical to understand how proteins interact with one another. These probes can be readily applied to visualize the actions of drugs on their targets in cells in facilitating drug screening for future drug discovery. Such biotechnology will have a significant impact on our understanding of the proteome -- the next frontier after the genome.
This project was supported by the Research Grants Council of Hong Kong, the emerging Strategic Research Theme (e-SRT) on Integrative Biology and the Wilson and Amelia Wong Endowment Fund in fostering our interdisciplinary collaborations.
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