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Here is a presentation of a long term, extensive research project. This is first of all an intellectual challenge aiming at knowing what could be done around biochemical pathways. My university training enables me to consider working on mathematical models of dynamical systems and I try to complete the overview of the interface between physics and biology, that I had during my master's degree, with more specialized recent knowledge on biochemical pathways.
In the frame of a PhD project, I consider delimitating a specific subproject and devolop it in full detail. Embedding this project in a wider frame will make it easy to identify how different scientific questions are related and how insights in a specific direction may inform another direction.
Biochemical pathways are the bottleneck between genetic information and molecular function (as well as between molecular function and genetic information).
Their non linear properties are associated to function, population[Llamosi 2016] and evolutionary questions[Maharjan 2012]. In particular, the activation and regulation of biochemical pathways is ensured by topological properties such as redundance[Nguyen 2012], which make the multiple parameters of these networks have optimal states[Berkhout 2012, Malukulta 2016]. The modification of kinetics under controlled external parameters inform on the intervals of function of biochemical pathways[Otero-Muras 2014, Bajic 2014].
Such pathways are influenced by a certain level of genome and phenotype variation influencing or not function[Yanagida 2015]. The accumulation of neutral variations (with regard to function) may enable adaptation to conditions of external stress[Barrick 2014]. Hence, the evolutionary trajectories of the genes that are the basis of the biochemical networks inform on the evolvability of function after accumulation of variation[Hosseini 2015].
The phylogeny of species with respect to classes of biochemical pathways informs on the rules of evolution of biochemical networks and on the mapping between genotype and phenotype[Morrisson 2016].
Biochemical pathways are included in a "modular" network involving the whole organism[Muto 2013]. External conditions activate and influence biochemical pathways, which may result in high level influence on the organism's phenotype[Cheng 2014] (see section PhD project questions).
Biochemical pathways are:
These properties leave the question of controllabity open. Pathway engineering enables to achieve specific goals such as production of biopharmaceuticals[Soons 2013] and influence phenotypes through pathway engineering[Fajas 2013].
The question of controllability leads to achievable goals and limitations[Villaverde 2016, Wang 2016].
Models of biochemical pathways exist for a vast number of different specific pathways and conditions[]. They are often valid in a limited scope. The analysis of experimental data as well as theoretical developments in the field of parameter optimization and model selection[Maiwald 2016] enable to improve biochemical pathways models[Bachmann 2012]. In a second step, these models may be used to study the controllability of biochemical pathways[Gates 2016].
Cancer could be linked to metabolism modification, with a loss of regulation of nutrient uptake by cells[Pavlova 2015]. The input-output models could be used to optimize cancer therapy through controlled diet.
http://www.pathwaycommons.org/
http://www.phylomedb.org/
https://www.bioconductor.org/packages/release/bioc/vignettes/pwOmics/inst/doc/pwOmics.pdf
looking for a lab
or open collaboration in the frame of the NumBio Lab
Operons https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2776167/ in particular as they exhibit non-linear behaviours http://rsif.royalsocietypublishing.org/content/5/Suppl_1/S29 https://www.ncbi.nlm.nih.gov/pubmed/17351004
evolutionary algorithms and architecture http://trr141.de http://www.aevol.fr
transition to multicellularity http://rsif.royalsocietypublishing.org/content/12/102/20140982.abstract
E-coli long term experiment http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1002444
Please visit https://gitlab.com/jibe-b/biochemical-pathways-non-linearity-evolution/issues and open an issue for any idea, question, remark. (unfortunately, gitlab doesn’t show in iframes, this will come through the gitlab API.)
Knowledge base management: I will convert as much content from the issue management system (gitlab) and the library (keeping track of attribution to contributors) into a RDF graph. I will then analyse the content of this database to valorise it.
(server under maintenance (in order to have a secure database). Please try sparql.open-scientist.org) or http://92.222.70.120:9999/blazegraph/sparql for updates )