NETCONTROLOGY | Controllability of biological networks

Summary
A dynamic system is controllable if, given suitable inputs, it can be driven from any initial state to any desired final state in finite time. Despite the advances in network science, computational approaches that can be used to characterize the dynamics of complex, biological systems are still lacking. This project aims at determining how biological networks can be controlled with focus on two cutting-edge case studies from medicine. Existing controllability approaches work essentially on graphs and do not consider other constraints typically arising in biological systems (e.g. steady-state). This strengthens the need for development of such methods. In this project, nonlinear, quantitative and dynamic network models will be developed for biological networks with multiple regulatory mechanisms. In these networks, it is vital to identify the subset of key components and regulatory interactions whose perturbation leads to the desirable functional changes. However, it is typically neither feasible, nor necessary to control the whole network. Instead, for many practical applications, it would suffice to control a preselected subsystem of target nodes. Besides full controllability, target controllability of the networks will also be addressed. Different measures will be developed to compare networks based on their controllability. The established network control principles will be exploited to (a) reprogram cancer networks through their druggable vulnerabilities to improve anticancer therapeutics (case study 1), and (b) target the enzymatic sources of relevant oxidative stress to support neuroprotection in stroke (case study 2).
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/841281
Start date: 06-01-2020
End date: 05-01-2023
Total budget - Public funding: 253 052,16 Euro - 253 052,00 Euro
Cordis data

Original description

A dynamic system is controllable if, given suitable inputs, it can be driven from any initial state to any desired final state in finite time. Despite the advances in network science, computational approaches that can be used to characterize the dynamics of complex, biological systems are still lacking. This project aims at determining how biological networks can be controlled with focus on two cutting-edge case studies from medicine. Existing controllability approaches work essentially on graphs and do not consider other constraints typically arising in biological systems (e.g. steady-state). This strengthens the need for development of such methods. In this project, nonlinear, quantitative and dynamic network models will be developed for biological networks with multiple regulatory mechanisms. In these networks, it is vital to identify the subset of key components and regulatory interactions whose perturbation leads to the desirable functional changes. However, it is typically neither feasible, nor necessary to control the whole network. Instead, for many practical applications, it would suffice to control a preselected subsystem of target nodes. Besides full controllability, target controllability of the networks will also be addressed. Different measures will be developed to compare networks based on their controllability. The established network control principles will be exploited to (a) reprogram cancer networks through their druggable vulnerabilities to improve anticancer therapeutics (case study 1), and (b) target the enzymatic sources of relevant oxidative stress to support neuroprotection in stroke (case study 2).

Status

TERMINATED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018