ChemChaste: Simulating spatially inhomogeneous biochemical reaction–diffusion systems for modeling cell–environment feedbacks
Connah G M Johnson, Alexander G Fletcher and Orkun S Soyer
Spatial organization plays an important role in the function of many biological systems, from cell fate specification in animal development to multistep metabolic conversions in microbial communities. The study of such systems benefits from the use of spatially explicit computational models that combine a discrete description of cells with a continuum description of one or more chemicals diffusing within a surrounding bulk medium. Here, we describe ChemChaste, an extension for the open-source C++ computational biology library Chaste. We describe ChemChaste and demonstrate its functionality using a selection of chemical and biochemical exemplars, with a focus on demonstrating increased ability in modeling bulk chemical reactions and their coupling with intracellular reactions.
Investigating the ultrafast dynamics and long-term photostability of an isomer pair, Usujirene and Palythene, from the Mycosporine-like amino acid family
Whittock, Abigail L, Wooley, Jack Matthew, Auckloo, Nazia, Corre, Christophe and Stavros, Vasilos G
Using a combination of natural product extraction/purification and femtosecond transient absorption spectroscopy, we studied the relaxation pathway for a common mycosporine-like amino acid pair, usujirene and its geometric isomer palythene, in the first few nanoseconds following photoexcitation. Our studies show that the electronic excited state lifetimes of these molecules persist for only a few hundred femtoseconds before the excited state population is funneled through an energetically accessible conical intersection with subsequent vibrational energy transfer to the solvent. We found that a minor portion of the isomer pair did not recover to their original state within 3 ns after photoexcitation.
Identification of novel aphid-killing bacteria to protect plants
Deepa Paliwal, Amanda H Hamilton, Glyn A Barrett, Fabrzio Alberti, Helmut van Emden, Caroline L Monteil, Tim H Mauchine, Ralf Nauen, Carol Wagstaff, Chris Bass, Robert W Jackson
Aphids, including the peach-potato aphid, Myzus persicae, are major insect pests of agriculture and horticulture, and aphid control measures are limited. Recent studies have shown that environmental microbes have varying abilities to kill insects. We screened a range of environmental bacteria isolates for their abilities to kill target aphid species. Tests demonstrated the killing aptitude of these bacteria against six aphid genera (including Myzus persicae). No single bacterial strain was identified that was consistently toxic to insecticide-resistant aphid clones than susceptible clones, suggesting resistance to chemicals is not strongly correlated with bacterial challenge. Our findings provide new insights into aphid susceptibility to bacterial infection with the aim of utilizing bacteria as effective biocontrol agents.
CMTr cap-adjacent 2`-O-ribose mRNA methyltransferases are required for reward learning and mRNA localization to synapses
Irmgard U. Haussmann, Yanying Wu , Mohanakarthik P. Nallasivan, Nathan Archer, Zsuzsanna Bodi, Daniel Hebenstreit , Scott Waddell , Rupert Fray , Matthias Soller
Cap-adjacent nucleotides of animal, protist and viral mRNAs can be O-methylated at the 2‘ position of the ribose (cOMe). The functions of cOMe in animals, however, remain largely unknown. Here we show that the two cap methyltransferases (CMTr1 and CMTr2) of Drosophila can methylate the ribose of the first nucleotide in mRNA. Among CMTr targets are cell adhesion and signaling molecules. Many are relevant for learning, and are also targets of Fragile X Mental Retardation Protein (FMRP). Like FMRP, cOMe is required for localization of untranslated mRNAs to synapses and enhances binding of the cap binding complex in the nucleus. Hence, our study reveals a mechanism to co-transcriptionally prime mRNAs by cOMe for localized protein synthesis at synapses.
Multisite Enzymes as a Mechanism for Bistability in Reaction Networks
Clarmyra Hayes, Elisenda Feliu, Orkun Soyer
Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate–enzyme complexes create a potential for bistable dynamics in such reaction networks. We construct a generic model of an enzyme with n-substrate binding sites and derive an analytical solution for the steady-state concentration of all enzyme–substrate complexes. By studying these expressions, we obtain a mechanistic understanding of bistability, derive parameter combinations that guarantee bistability, and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction networks involving multisite enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multisite enzymes.
Genome-wide chromosomal association of Upf1 is linked to Pol II transcription in Schizosaccharomyces pombe
Sandip De, David M. Edwards, Vibha Dwivedi, Jianming Wang, Wazeer Varsally, Hannah L. Dixon, Anand K. Singh, Precious O. Owuamalam, Matthew T. Wright, Reece P. Summers, Md Nazmul Hossain, Emily M. Price, Marcin W. Wojewodzic, Francesco Falciani, Nikolas J. Hodges, Marco Saponaro, Kayoko Tanaka, Claus M. Azzalin, Peter Baumann, Daniel Hebenstreit and Saverio Brogna
Although the RNA helicase Upf1 has hitherto been examined mostly in relation to its cytoplasmic role in nonsense mediated mRNA decay (NMD), here we report high-throughput ChIP data indicating genome-wide association of Upf1 with active genes in Schizosaccharomyces pombe. This association is RNase sensitive, correlates with Pol II transcription and mRNA expression levels. A significant proportion of the genes associated with Upf1 in wild-type conditions are also mis-regulated in upf1Δ. These data envisage that by operating on the nascent transcript, Upf1 might influence Pol II phosphorylation and transcription.