Descripción del proyecto
Modelado de la morfogénesis ramificada
Algunos órganos, como por ejemplo los pulmones y los riñones, requieren un elevado ratio de superficie a volumen para funcionar, por lo que se crean estructuras tubulares muy ramificadas durante un proceso de desarrollo denominado morfogénesis ramificada. Los mecanismos, la señalización molecular y la reorganización celular necesarios para la creación de la estructura de los órganos siguen siendo cuestiones fundamentales abiertas. El proyecto financiado con fondos europeos Demos utilizará métodos teóricos para comprender cómo las normas estocásticas dan lugar a la morfogénesis orgánica, incluida la coordinación bidireccional del destino de las células individuales. Los investigadores aplicarán su amplia experiencia en el modelado de interacciones citoesqueléticas, dinámica de células madre y procesos de ramificación en general combinando enfoques de biología de sistemas y enfoques biofísicos a distintas escalas.
Objetivo
Branching morphogenesis, the process by which branched organs such as the lung, prostate, kidney or mammary gland are generated, is a paradigmatic example of complex developmental processes bridging multiple scales. The mechanisms through which given molecular signals and cellular behaviours give rise to a robust organ structure remains a fundamental and open question, for which theoretical methods are needed. Our experience in modelling cytoskeletal mechanics, stem cell dynamics and branching processes puts us in a unique position to tackle this fascinating problem, by combining systems biology and biophysical approaches at multiple scales. In particular, we will focus on:
1. Understanding how stochastic rules lead to robust morphogenetic outputs at the organ scale, and which constraints and optimal design principles they impose on physiological function.
2. Characterizing at the cellular scale the bi-directional feedbacks coordinating fate choices of stem/progenitor cells and niche signals during the extensive remodelling events that branching morphogenesis entails.
3. Developing at the subcellular and cellular scale an integrated mechanochemical theory of pattern formation in branched organs, to understand the coordination of mechanical forces and chemical signals defining their global structure.
Towards these goals, we will combine analytical and numerical tools with data analysis methods, to reach a quantitative understanding of the emergent mechanisms driving branching morphogenesis. We will challenge our theoretical predictions with published datasets available for different organs, as well as design specific experimental tests in collaboration with experimental biology groups. This will allow us to compare and contrast different systems, and extract generic classes of design principles of organogenesis across length scales. With this, we expect to generate novel insights of broad relevance for the fields of systems, computational and developmental biology.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
3400 Klosterneuburg
Austria