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LH14009

Instabilities and dynamics of functional motifs in biochemical networks

Project goals

General aim of the proposed Czech?American scientific cooperation project is on oscillatory dynamics and wave phenomena in biochemical regulatory networks. Within the cell assemblages there are many signalling and regulatory mechanisms that involve positive and negative feedback, a classical example that will be part of the project are phosphorylation cascades mediated by mitogen-activated protein kinases (MAPK). From the mechanistic point of view, such processes are represented by sequences of enzyme-catalyzed steps, which can be represented as reaction networks. To describe such networks, a number of theories has been proposed. A particular approach called stoichiometric network analysis helps to identify core subnetworks responsible for instabilities leading to a specific dynamical behavior, such as oscillations or bistability. These dynamical modes are of great importance in understanding both chemical and biological processes, of specific interest here is autocrine regulation and switches. The aim of the project is to contribute to understanding the relation between topological structure of a specific network - a motif - and its dynamical behavior through which it performs a biological function. Particular cases will include occurrence of oscillations in MAPK cascades and role of these dynamics in the wave spreading in autocrine signalling. Furthermore, functional motifs in biochemical systems occurring throughout the literature will be interpreted using the stoichiometric network methodology which will lead to a deeper understanding what are the specific features leading to dynamical instabilities and to a classification system based on the aforementioned features in the network's topology.

Keywords

biochemical networksoscillatory motifsintercellularcelular signallingreaction-diffusion wavesreaction network classificationstability and bifurcations

Public support

  • Provider

    Ministry of Education, Youth and Sports

  • Programme

    KONTAKT II

  • Call for proposals

    KONTAKT II 4 (SMSM2014LH4)

  • Main participants

    Vysoká škola chemicko-technologická v Praze / Fakulta chemicko-inženýrská

  • Contest type

    VS - Public tender

  • Contract ID

    MSMT-9919/2014-1

Alternative language

  • Project name in Czech

    Nestability a dynamika funkčních motivů v biochemických sítích

  • Annotation in Czech

    Projekt je zaměřen na studium dynamiky enzymových reakčních sítí a jejich interakcí s procesy přenosu chemického signálu v buněčných systémech. V rámci projektu bude analyzována fosforylační MAPK kaskáda a pomocí teorie chemických sítí v ní bude identifikováno jádro zodpovědné za vznik oscilačního chování. Na modelu jádra bude vysvětlen původ oscilací. Nalezené jádro bude využito při studiu autokrinní komunikace, kde bude tvořit prvek zpětnovazební smyčky propojující děje na transmembránových receptorech a děje spojené s vylučováním nové signální molekuly. Budou identifikovány a kategorizovány typy buněčných odpovědí ve formě chemických koncentračních vln různých typů v závislosti na nastavení kinázového jádra. Budou též zkoumány, identifikovány a kategorizovány funkční motivy ve vybraných biochemických sítích, které vedou ke vzniku oscilačního chování popřípadě dalších nestabilit. Bude položen základ klasifikace funkčních motivů na základě topologie reakční sítě s využitím matematicky přesných postupů.

Scientific branches

  • R&D category

    ZV - Basic research

  • CEP classification - main branch

    CI - Industrial chemistry and chemical engineering

  • CEP - secondary branch

    CF - Physical chemistry and theoretical chemistry

  • CEP - another secondary branch

    BO - Biophysics

  • 10403 - Physical chemistry
    10610 - Biophysics
    20401 - Chemical engineering (plants, products)
    20402 - Chemical process engineering

Completed project evaluation

  • Provider evaluation

    V - Vynikající výsledky projektu (s mezinárodním významem atd.)

  • Project results evaluation

    A minimal model of MAPK cascade was formulated based on competitive autocatalysis involving phosphorylation/dephophorylation. Travelling waves during autocine signalling above epithelial tissue using the MAPK model was studied. We proposed a method for parameter estimation based on dominant oscillatory motifs. Results are compiled in 4 publications to be submitted to leading journals in the field

Solution timeline

  • Realization period - beginning

    Apr 1, 2014

  • Realization period - end

    Dec 31, 2016

  • Project status

    U - Finished project

  • Latest support payment

    Feb 18, 2016

Data delivery to CEP

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

  • Data delivery code

    CEP17-MSM-LH-U/01:1

  • Data delivery date

    Jun 23, 2017

Finance

  • Total approved costs

    1,564 thou. CZK

  • Public financial support

    1,564 thou. CZK

  • Other public sources

    0 thou. CZK

  • Non public and foreign sources

    0 thou. CZK

Recognised costs

1 564 CZK thou.

Public support

1 564 CZK thou.

0%


Provider

Ministry of Education, Youth and Sports

CEP

CI - Industrial chemistry and chemical engineering

Solution period

01. 04. 2014 - 31. 12. 2016