Carregant...
Fitxers
Tipus de document
TesiVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/102417
Fluctuations, gene circuit architecture and stem cell quiescence
Títol de la revista
Autors
ISSN de la revista
Títol del volum
Resum
[eng] Biological development is a complex process in which, from a single cell, a whole multicellular organism arises. The formation of this intrincate structures requires a very precise regulation in space and time. This regulation involves a network of proteins and genes that interact. These interactions give rise to nonlinear behaviours, of the same kind that physicists have studied in other systems. Furthermore, cellular processes are often subject to fluctuations, a problem that has been studied by out of equilibrium statistical mechanics. These facts mean that the tools from nonlinear physics and statistical mechanics are suitable to study problems in the biological context and, at the same time, these problems are of interest to physcists. In this thesis we study small gene circuits that generate bistability, the property of having two stable states upon the same input. In the first part of the thesis, we study at a theoretical level how the architecture of these circuits interacts with stochasticity. We first study a simple autoactivating Positive Feedback Loop, in which a protein activates its own production. We compare how fluctuations affect the system when they are added as a simple perturbation to the deterministic system (additive noise) or when they are derived from the dynamics of the system (multiplicative noise). We also show that multiplicative noise is able to reproduce the experimentally observed result of asymmetric stochastic switching, in which it is easier to escape from a high concentration state to a low concentration state than vice versa. We also compare how noise from diferent sources affects five bistable circuits with different architectures, and find that the sensitivity of the stability of the states to each noise source depends greatly on the circuit considered. This suggests that they could be found in different biological contexts and functions. In a second part of the thesis, we study the quiescent centre of plant {\em Arabidopsis Thaliana}. This quiescent centre is formed by a group of stem cells that organize the different stem cell types surrounding them, and have the property of rarely dividing called quiescence. Thanks to a collaboration with the plant developmental biology group led by Dr. Ana I. Ca\-no-Delgado at Center for Research in Agricultural Genomics (CRAG), we are able to study a gene circuit that regulates quiescence. Our collaborators discovered BRAVO, a protein that regulates quiescence, and unveiled its interactions with BES1, that regulates many proteins according to the signalling of the Brassinosteroid hormone family and promotes divisions (releasing quiescence). Our mathematical modelling shows that the dimerization of BRAVO and BES1 enables strongly opposed states of these proteins, ensuring unequivocal regulation of quiescence, and a sharp transition from a [HIGH BRAVO, LOW BES1] state to a [LOW BRAVO, HIGH BES1] state upon Brassinosteroid signalling. We also add to this module a third protein, WOX5, that is only expressed in the quiescent centre and has been shown to directly regulate quiescence, and find that this opposed states and sharp transitions are preserved.
Descripció
Matèries (anglès)
Citació
Citació
FRIGOLA TUBERT, David. Fluctuations, gene circuit architecture and stem cell quiescence. [consulta: 28 de novembre de 2025]. [Disponible a: https://hdl.handle.net/2445/102417]