Ricksen Surya Winardhi
Email Address
pharsw@nus.edu.sg
Organizational Units
SCIENCE
faculty
PHYSICS
dept
PHARMACY
dept
SPECIALTY RESEARCH INST/CTRS
faculty
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Publication Search Results
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Publication Dynamics of Equilibrium Folding and Unfolding Transitions of Titin Immunoglobulin Domain under Constant Forces(American Chemical Society, 2015) Chen Hu; Yuan Guohua; RICKSEN SURYA WINARDHI; Yao Mingxi; Popa Ionel; Fernandez Julio M.; Yan Jie; MECHANOBIOLOGY INSTITUTEPublication Theoretical methods for studying DNA structural transitions under applied mechanical constraints(2017) Efremov, A.K; Winardhi, R.S; Yan, J; MECHANOBIOLOGY INSTITUTE; PHYSICSRecent progress in single-molecule manipulation technologies has made it possible to exert force and torque on individual DNA biopolymers to probe their mechanical stability and interaction with various DNA-binding proteins. It was revealed in these experiments that the DNA structure and formation of nucleoprotein complexes by DNA-architectural proteins can be strongly modulated by an intricate interplay between the entropic elasticity of DNA and its global topology, which is closely related to the mechanical constraints applied to the DNA. Detailed understanding of the physical processes underlying the DNA behavior observed in single-molecule experiments requires the development of a general theoretical framework, which turned out to be a rather challenging task. Here, we review recent advances in theoretical methods that can be used to interpret single-molecule manipulation experiments on DNA. © 2017 by the authors; licensee MDPI, Basel, Switzerland.Publication Single-molecule study on histone-like nucleoid-structuring protein (H-NS) paralogue in Pseudomonas aeruginosa: MvaU Bears DNA organization mode similarities to MvaT(Public Library of Science, 2014) RICKSEN SURYA WINARDHI; Castang S.; Dove S.L.; Yan J.; SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH; PAEDIATRICS; BIOCHEMISTRYPublication Non-canonical activation of OmpR drives acid and osmotic stress responses in single bacterial cells(Nature Publishing Group, 2017) Chakraborty S.; Winardhi R.S.; Morgan L.K.; Yan J.; Kenney L.J.; MECHANOBIOLOGY INSTITUTE; PHYSICSUnlike eukaryotes, bacteria undergo large changes in osmolality and cytoplasmic pH. It has been described that during acid stress, bacteria internal pH promptly acidifies, followed by recovery. Here, using pH imaging in single living cells, we show that following acid stress, bacteria maintain an acidic cytoplasm and the osmotic stress transcription factor OmpR is required for acidification. The activation of this response is non-canonical, involving a regulatory mechanism requiring the OmpR cognate kinase EnvZ, but not OmpR phosphorylation. Single cell analysis further identifies an intracellular pH threshold ~6.5. Acid stress reduces the internal pH below this threshold, increasing OmpR dimerization and DNA binding. During osmotic stress, the internal pH is above the threshold, triggering distinct OmpR-related pathways. Preventing intracellular acidification of Salmonella renders it avirulent, suggesting that acid stress pathways represent a potential therapeutic target. These results further emphasize the advantages of single cell analysis over studies of population averages. © 2017 The Author(s).