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
Basic information
Recognised costs
1 564 CZK thou.
Public support
1 564 CZK thou.
100%
Provider
Ministry of Education, Youth and Sports
CEP
CI - Industrial chemistry and chemical engineering
Solution period
01. 04. 2014 - 31. 12. 2016