{"title":"Unraveling T-cell dynamics using fluorescent timer: Insights from the Tocky system.","authors":"Masahiro Ono","doi":"10.2142/biophysico.bppb-v21.s010","DOIUrl":"10.2142/biophysico.bppb-v21.s010","url":null,"abstract":"<p><p>Understanding the temporal dynamics of T-cell transcription is crucial for insights into immune cell function and development. In this study, we show the features of the Timer-of-Cell-Kinetics-and-Activity (Tocky) system, which enables analysis of temporal dynamics of cell activities and differentiation, leveraging Fluorescent Timer protein, which spontaneously changes its emission spectrum from blue to red fluorescence in known kinetics, as reporters. The current study examines the properties of the Tocky system, highlighting the Timer-Angle approach, which is a core algorithm of Tocky analysis and converts Timer Blue and Red fluorescence into Timer Angle and Intensity by trigonometric transformation. Importantly, Tocky analyzes time-related events within individual cells by the two phases of measurements, distinguishing between (1) the temporal sequence of cellular activities and differentiation within the time domain, and (2) the transcription frequency within the frequency domain. The transition from time measurement to frequency analysis, particularly at the Persistent locus that bridges these domains, highlights that system's unique property in what is measured and analyzed by Tocky. Intriguingly, the sustained transcriptional activities observed in cells at the Persistent locus may have unique biological features as demonstrated in activated regulatory T-cells (Treg) and pathogenic T-cells, respectively, using Foxp3-Tocky and Nr4a3-Tocky models. In conclusion, the Tocky system can provide crucial data for advancing our understanding of T-cell dynamics and function.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211010"},"PeriodicalIF":1.6,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chromophore-assisted light inactivation of target proteins for singularity biology.","authors":"Hisashi Shidara, Susumu Jitsuki, Kiwamu Takemoto","doi":"10.2142/biophysico.bppb-v21.s009","DOIUrl":"10.2142/biophysico.bppb-v21.s009","url":null,"abstract":"<p><p>Singularity phenomena are rare events that occur only with a probability of one in tens of thousands and yet play an important role in the fate of the entire system. Recently, an ultra-wide-field microscopy imaging systems, AMATERAS, have been developed to reliably capture singularity phenomena. However, to determine whether a rare phenomenon captured by microscopy is a true singularity phenomenon-one with a significant impact on the entire system-, causal analysis is required. In this section, we introduce the CALI method, which uses light to inactivate molecules as one of the techniques enabling causal analysis. In addition, we discuss the technical innovations of the CALI method that are required to contribute to the future development of singularity biology.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211009"},"PeriodicalIF":1.6,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Elucidating molecular and cellular mechanisms of singularity phenomena in immunology.","authors":"Taku Okazaki, Tomoya Katakai","doi":"10.2142/biophysico.bppb-v21.s007","DOIUrl":"10.2142/biophysico.bppb-v21.s007","url":null,"abstract":"","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211007"},"PeriodicalIF":1.6,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A battle between two biological singularities: Immune response vs. cancer.","authors":"Tomoya Katakai, Taku Okazaki","doi":"10.2142/biophysico.bppb-v21.s006","DOIUrl":"10.2142/biophysico.bppb-v21.s006","url":null,"abstract":"<p><p>In a post-growth multicellular organism, the phenomenon in which a small number of rare cells can be the starting point for inducing a dramatic change in the entire system is considered a \"biological singularity.\" The immune response and cancer can be regarded as singularity phenomena in mammals, but their nature is fundamentally different. The immune response is considered a \"programmed\" singularity, whereas cancer is an \"unprogrammed\" singularity. These two systems perpetually engage in a cycle of attack and defense within the organism. The outcome is depending on the wining system, which determines whether the individual experiences a state resembling light or darkness. However, the overall mechanism of the competition remains unclear and is expected to be elucidated with future innovations in bioimaging technologies. Immune checkpoint blockade therapy is a means by which the two singularity balances can be artificially manipulated; therefore, mechanistic insight is necessary for cancer treatment strategies. Altogether, these findings provide a different perspective crucial for understanding the behavior of dynamic cell populations in multicellular organisms.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211006"},"PeriodicalIF":1.6,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integration of single-cell manipulation, whole transcriptome analysis, and image-based deep learning for studying \"Singularity Biology\".","authors":"Katsuyuki Shiroguchi","doi":"10.2142/biophysico.bppb-v21.s005","DOIUrl":"10.2142/biophysico.bppb-v21.s005","url":null,"abstract":"","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211005"},"PeriodicalIF":1.6,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current advances in the development of bioluminescent probes toward spatiotemporal trans-scale imaging.","authors":"Akihiro Sakama, Mariko Orioka, Yuki Hiruta","doi":"10.2142/biophysico.bppb-v21.s004","DOIUrl":"10.2142/biophysico.bppb-v21.s004","url":null,"abstract":"<p><p>Bioluminescence imaging has recently attracted great attention as a highly sensitive and non-invasive analytical method. However, weak signal and low chemical stability of the luciferin are conventional drawbacks of bioluminescence imaging. In this review article, we describe the recent progress on the development and applications of bioluminescent probes for overcoming the aforementioned limitations, thereby enabling spatiotemporal trans-scale imaging. The detailed molecular design for manipulation of their luminescent properties and functions enabled a variety of applications, including <i>in vivo</i> deep tissue imaging, long-term imaging, and chemical sensor.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211004"},"PeriodicalIF":1.6,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Search for singularity cells at the onset of brain disorders using whole-brain imaging.","authors":"Hitoshi Hashimoto, Takanobu Nakazawa","doi":"10.2142/biophysico.bppb-v21.s003","DOIUrl":"10.2142/biophysico.bppb-v21.s003","url":null,"abstract":"","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 Supplemental","pages":"e211003"},"PeriodicalIF":1.6,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pioneering artificial cell-like structures with DNA nanotechnology-based liquid-liquid phase separation.","authors":"Yusuke Sato, Masahiro Takinoue","doi":"10.2142/biophysico.bppb-v21.0010","DOIUrl":"10.2142/biophysico.bppb-v21.0010","url":null,"abstract":"<p><p>Recent studies have revealed that liquid-liquid phase separation (LLPS) plays crucial roles in various cellular functions. Droplets formed via LLPS within cells, often referred to as membraneless organelles, serve to concentrate specific molecules, thus enhancing biochemical reactions. Artificial LLPS systems have been utilized to construct synthetic cell models, employing a range of synthetic molecules. LLPS systems based on DNA nanotechnology are particularly notable for their designable characteristics in droplet formation, dynamics, properties, and functionalities. This review surveys recent advancements in DNA-based LLPS systems, underscoring the programmability afforded by DNA's base-pair specific interactions. We discuss the fundamentals of DNA droplet formation, including temperature-dependence and physical properties, along with the precise control achievable through sequence design. Attention is given to the phase separation of DNA nanostructures on two-dimensional closed interfaces, which results in spatial pattern formation at the interface. Furthermore, we spotlight the potential of DNA droplet computing for cancer diagnostics through specific microRNA pattern recognition. We envision that DNA-based LLPS presents a versatile platform for the exploration of cellular mimicry and opens innovative ways for the development of functional synthetic cells.</p>","PeriodicalId":101323,"journal":{"name":"Biophysics and physicobiology","volume":"21 1","pages":"e210010"},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11128300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}