Modeling biological networks: from single gene systems to large microbial communities

TL;DR

This paper explores biological networks at cellular and community levels, analyzing gene autoregulation dynamics and modeling microbial abundance distributions to understand complex biological systems.

Contribution

It introduces a detailed study of autoregulation effects in gene networks and develops models for microbial community dynamics, bridging single-gene and ecosystem scales.

Findings

Autorepression speeds response times in gene regulation.

Autoactivation can cause multiple stable states.

Models can replicate microbial abundance distributions.

Abstract

In this research, we study biological networks at different scales: a gene autoregulatory network at the single-cell level and the gut microbiota at the population level. Proteins are the main actors in cells, they are the building blocks, act as enzymes and antibodies. The production of proteins is mediated by transcription factors. In some cases, a protein acts as its own transcription factor, this is called autoregulation. It is known that autorepression speeds up the response and that autoactivation can lead to multiple stable equilibria. In this thesis, we study the effects of the combination of activation and repression in autoregulation, as a case study we investigate the possible dynamics of the leucine responsive protein B of the archaeon Sulfolobus solfataricus (Ss-LrpB), a protein that regulates itself in a unique and non-monotonic way via three binding boxes. We examine for which conditions this type of network leads to oscillations or bistability. In the second part, much larger biological systems are considered. Ecological systems, among which the human gut microbiome, are characterized by heavy-tailed abundance profiles. We study how these distributions can arise from population-based models by adding saturation effects and linear noise. Moreover, we examine different characteristics of experimental time series of microbial communities, such as the noise color and neutrality of the biodiversity, and look at the influence of the parameters on these characteristics. With the first research topic we want to lay a foundation for the understanding of non-monotonic gene regulation and take the first steps toward synthetic biology in archaea. In the second part of the thesis, we investigate experimental time series from complex ecosystems and seek theoretical models reproducing all observed characteristics in view of building predictive models.