Descripción del proyecto
Nuevas formas de controlar las redes biológicas
Los elementos biológicos interactúan entre sí y forman redes. La capacidad de controlar sus dinámicas es fundamental para la investigación científica, especialmente en los sectores farmacéutico y médico. A pesar de los avances en ciencia de redes, todavía faltan los enfoques computacionales necesarios. El proyecto NETCONTROLOGY explorará cómo las redes biológicas pueden controlarse centrándose en dos estudios médicos pioneros: reprogramar las redes del cáncer (encontrando vulnerabilidades ante los fármacos para mejorar las terapias contra el cáncer) y centrarse en las fuentes enzimáticas de estrés oxidativo para reforzar la neuroprotección en caso de accidente cerebrovascular. Para ello, el proyecto desarrollará modelos de red dinámicos, cuantitativos y lineares para redes biológicas con múltiples mecanismos reguladores. Además, desarrollará diversas medidas para comparar las redes basadas en su controlabilidad.
Objetivo
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).
Ámbito científico
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Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
6200 MD Maastricht
Países Bajos