Ribosome traffic on mRNAs maps to gene ontology : genome-wide quantification of translation initiation rates and polysome size regulation

Peer reviewedPublisher PD

Identification of the mRNA targets of tRNA-specific regulation using genome-wide simulation of translation

FUNDING Biotechnology and Biological Sciences Research Council (BBSRC) [BB/I020926/1 to I.S.]; BBSRC PhD studentship award [C103817D to I.S. and M.C.R.]; Scottish Universities Life Science Alliance PhD studentship award (to M.C.R. and I.S.]. Funding for open access charge: BBSRC. Conflict of interest statement. None declared.Peer reviewedPublisher PD

Analysing GCN4 Translational Control in Yeast by Stochastic Chemical Kinetics Modelling and Simulation

Peer reviewedPublisher PD

Torque measurement in real time during mixing and kneading of bread dough with high content of resistant maize starch and enzymes

In this work, a methodology to measure torque during dough mixing in large scale was developed and the baking performance of bread dough formulated with resistant starch (RS) and enzymes was evaluated. Dough was formulated with 12.5 g/100 g of RS and 4 mg/100 g of a mixture of enzymes, glucose-oxidase (Gox), tranglutaminase (TG) and xylanase (HE) in proportions according to a three-component mixture design of experiments. Dough was mixed in a large-scale dynamic rheometer measuring instant torque and speed in real time through a personal computer (PC) interface. Maximum torque during mixing and parameters of the dough development curves obtained from rheofermentometer were fit to mathematical models within 95 % of confidence. Gox and TG showed positive effects on the maximum height of dough, while HE showed a negative one. Also, it was found that Gox and TG in the presence of HE could be important for reducing dough weakening.Fil: Altuna, Luz. Universidade de Sao Paulo; BrasilFil: Romano, Roberto C. O.. Universidade de Sao Paulo; BrasilFil: Pileggi, Rafael G.. Universidade de Sao Paulo; BrasilFil: Ribotta, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Ciencia y Tecnología de Alimentos Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Ciencia y Tecnología de Alimentos Córdoba; ArgentinaFil: Tadini, Carmen C.. Universidade de Sao Paulo; Brasi

Stepping and crowding of molecular motors: statistical kinetics from an exclusion process perspective

Motor enzymes are remarkable molecular machines that use the energy derived from the hydrolysis of a nucleoside triphosphate to generate mechanical movement, achieved through different steps that constitute their kinetic cycle. These macromolecules, nowadays investigated with advanced experimental techniques to unveil their molecular mechanisms and the properties of their kinetic cycles, are implicated in many biological processes, ranging from biopolymerisation (e.g. RNA polymerases and ribosomes) to intracellular transport (motor proteins such as kinesins or dyneins). Although the kinetics of individual motors is well studied on both theoretical and experimental grounds, the repercussions of their stepping cycle on the collective dynamics still remains unclear. Advances in this direction will improve our comprehension of transport process in the natural intracellular medium, where processive motor enzymes might operate in crowded conditions. In this work, we therefore extend the current statistical kinetic analysis to study collective transport phenomena of motors in terms of lattice gas models belonging to the exclusion process class. Via numerical simulations, we show how to interpret and use the randomness calculated from single particle trajectories in crowded conditions. Importantly, we also show that time fluctuations and non-Poissonian behavior are intrinsically related to spatial correlations and the emergence of large, but finite, clusters of co-moving motors. The properties unveiled by our analysis have important biological implications on the collective transport characteristics of processive motor enzymes in crowded conditions.Comment: 9 pages, 6 figures, 2 supplementary figure

ExpressInHost : A codon tuning tool for the expression of recombinant proteins in host microorganisms

Funding Information This work was performed as part of the Innovate UK project “Predictive optimisation of biocatalyst production for high-value chemical manufacturing” (Project Number TP101439). The current position of A.R. is funded by the German federal and state programme Professorinnenprogramms III for female scientists.Peer reviewedPublisher PD

ExpressInHost: A codon tuning tool for the expression of recombinant proteins in host microorganisms

ExpressInHost (https://gitlab.com/a.raguin/expressinhost) is a GTK/C++ based user friendly graphical interface that allows tuning the codon sequence of an mRNA for recombinant protein expression in a host microorganism. Heterologous gene expression is widely implemented in biotechnology companies and academic research laboratories. However, expression of recombinant proteins can be challenging. On the one hand, maximising translation speed is important, especially in scalable production processes relevant to biotechnology companies, but on the other hand, solubility problems often arise as a consequence, since translation "pauses" might be key to allow the nascent polypeptide chain to fold appropriately. To address this challenge, we have developed a software that offers three distinct modes to tune codon sequences using the genetic code redundancy. The tuning strategies implemented take into account the specific tRNA resources of the host and that of the native organism. They balance rapid translation and native speed mimicking to allow proper protein folding, thereby avoiding protein solubility problems

Introduction to Focus Issue : Dynamics in Systems Biology

Peer reviewedPublisher PD

Transport on a Lattice with Dynamical Defects

Many transport processes in nature take place on substrates, often considered as unidimensional lanes. These unidimensional substrates are typically non-static: affected by a fluctuating environment, they can undergo conformational changes. This is particularly true in biological cells, where the state of the substrate is often coupled to the active motion of macromolecular complexes, such as motor proteins on microtubules or ribosomes on mRNAs, causing new interesting phenomena. Inspired by biological processes such as protein synthesis by ribosomes and motor protein transport, we introduce the concept of localized dynamical sites coupled to a driven lattice gas dynamics. We investigate the phenomenology of transport in the presence of dynamical defects and find a novel regime characterized by an intermittent current and subject to severe finite-size effects. Our results demonstrate the impact of the regulatory role of the dynamical defects in transport, not only in biology but also in more general contexts

Deciphering mRNA Sequence Determinants of Protein Production Rate

5 pages, 3 figures, Supplemental Material (3 pages)One of the greatest challenges in biophysical models of translation is to identify coding sequences features that affect the rate of translation and therefore the overall protein production in the cell. We propose an analytic method to solve a translation model based on the inhomogeneous totally asymmetric simple exclusion process, which allow us to unveil simple design principles of nucleotide sequences determining protein production rates. Our solution shows an excellent agreement when compared to numerical genome-wide simulations of S. cerevisiae transcript sequences and predicts that the first 10 codons, together with the value of the initiation rate, are the main determinants of protein production rate. Finally, we interpret the obtained analytic results based on the evolutionary role of codons' choice for regulating translation rates and ribosome densities