Precision control of molecular activities and chemical reactions in live cells is a long-sought capability by life scientists. No existing technology can probe molecular targets in cells and simultaneously control the activities of only these targets at high spatial precision. We develop a real-time precision opto-control (RPOC) technology that detects a chemical-specific optical response from molecular targets during laser scanning and uses the optical signal to couple a separate laser to only interact with these molecules without affecting other sample locations. We demonstrate precision control of molecular states of a photochromic molecule in different regions of the cells. We also synthesize a photoswitchable compound and use it with RPOC to achieve site-specific inhibition of microtubule polymerization and control of organelle dynamics in live cells. RPOC can automatically detect and control biomolecular activities and chemical processes in dynamic living samples with submicron spatial accuracy, fast response time, and high chemical specificity.
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http://dx.doi.org/10.1038/s41467-022-32071-z | DOI Listing |
World J Microbiol Biotechnol
January 2025
Clinical Medical College, Changchun University of Chinese Medicine, Changchun, China.
In addressing the formidable challenge posed by methicillin-resistant Staphylococcus aureus (MRSA), this investigation elucidates a novel therapeutic paradigm by specifically targeting the virulence factor sortase A (SrtA) utilizing Tubuloside A (TnA). SrtA plays a critical role in the pathogenicity of MRSA, primarily by anchoring surface proteins to the bacterial cell wall, which is crucial for the bacterium's ability to colonize and infect host tissues. By inhibiting SrtA, TnA offers a novel and distinct strategy compared to traditional antibiotics.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
College of Biological Engineering, Qingdao University of Science and Technology, Qingdao 266042, China. Electronic address:
Although immune checkpoint inhibitors specifically targeting the PD-1/PD-L1 axis have exhibited remarkable clinical success, they are not uniformly effective across all patient cohorts. Immunotoxins, a novel class of cancer therapeutics, offering a promising alternative. PD-L1, which is also present in certain normal tissues, limits its suitability as an ideal target for immunotoxins.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Life Science and Medical Bioscience, Laboratory of Cytoskeletal Logistics, Graduate School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, Japan.
In mammalian epithelial cells, cytoplasmic microtubules are mainly non-centrosomal, through the functions of the minus-end binding proteins CAMSAP2 and CAMSAP3. When cells enter mitosis, cytoplasmic microtubules are reorganized into the spindle composed of both centrosomal and non-centrosomal microtubules. The function of the CAMSAP proteins upon spindle assembly remains unknown, as these do not exhibit evident localization to spindle microtubules.
View Article and Find Full Text PDFJ Interferon Cytokine Res
January 2025
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Suppressor of cytokine signaling (SOCS) 1 is a key negative regulator of interferon (IFN), interleukin (IL)12, and IL-2 family cytokine signaling through inhibition of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. To investigate the temporal induction of SOCS1 in response to cytokine in live cells and its selective regulation of signaling pathways, we generated a mouse expressing a Halo-tag-SOCS1 fusion protein (Halo-SOCS1) under control of the endogenous promoter. Homozygous Halo-SOCS1 mice () were viable with minor T cell abnormalities, most likely due to enhanced Halo-SOCS1 expression in thymocytes compared with the untagged protein.
View Article and Find Full Text PDFElife
January 2025
Eikon Therapeutics Inc, Hayward, United States.
The regulation of cell physiology depends largely upon interactions of functionally distinct proteins and cellular components. These interactions may be transient or long-lived, but often affect protein motion. Measurement of protein dynamics within a cellular environment, particularly while perturbing protein function with small molecules, may enable dissection of key interactions and facilitate drug discovery; however, current approaches are limited by throughput with respect to data acquisition and analysis.
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