568 research outputs found
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
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