Algorithmic Information Theory (AIT), also known as Kolmogorov complexity, is a quantitative approach to defining information. AIT is mainly used to measure the amount of information present in the observations of a given phenomenon. In this dissertation we explore the applications of AIT in two case studies. The first examines bright field cell image segmentation and the second examines the information complexity of multicellular patterns. In the first study we demonstrate that our proposed AIT-based algorithm provides an accurate and robust bright field cell segmentation. Cell segmentation is the process of detecting cells in microscopy images, which is usually a challenging task for bright field microscopy due to the low contrast of the images. In the second study, which is the primary contribution of this dissertation, we employ an AIT-based algorithm to quantify the complexity of information content that arises during the development of multicellular organisms. We simulate multicellular organism development by coupling the Gene Regulatory Networks (GRN) within an epithelial field. Our results show that the configuration of GRNs influences the information complexity in the resultant multicellular patterns.

No description available.

No description available.

No description available.

The field of functional genomics aims to understand the complex relationship between genotype and phenotype by integrating genome-wide approaches, such as transcriptomics, proteomics, and metabolomics. Large-scale "-omics" research has been made widely possible by the advent of high-throughput techniques, such as next-generation sequencing and mass-spectrometry. The vast data generated from such studies provide a wealth of information on the biological dynamics underlying phenotypes. Though functional genomics approaches are used extensively in human disease research, their use also spans organisms as miniscule as mycoplasmas to as great as sperm whales. In particular, functional genomics is instrumental in agricultural advancements for the improvement of productivity and sustainability in crop and livestock production. Improvement in soybean production is especially imperative, as soybeans are a primary source of oil and protein for human and livestock consumption, respectively. The research presented here employs functional genomics approaches – transcriptomics and metabolomics – to discern the transcriptional regulation and metabolic events underlying two economically important agronomic traits in soybean: seed phytic acid content and Soybean mosaic virus resistance. At normal levels, seed phytic acid content inhibits mineral absorption in humans and livestock, acting as an antinutrient and contributing to phosphorus pollution; however, the development of low phytic acid soybeans has helped mitigate these issues, as their seeds increase nutrient bioavailability and reduce environmental impact. Despite these desirable qualities, low phytic acid soybeans exhibit poor seed performance, which negatively affects germination rates and yield and has prevented their large-scale commercial production. Thus, part of the focus of this research was investigating the effects of mutations conferring the low phytic acid phenotype on seed germination. Comparative studies between low and normal phytic acid soybean seeds were carried out and revealed distinct differences in metabolite profiles and in the transcriptional regulation of biological pathways that may be vital for successful seed germination. The final part of this research concerns Rsv3-mediated extreme resistance, a unique mode of resistance that is effective against the most virulent strains of Soybean mosaic virus. The molecular mechanisms governing this type of resistance are poorly characterized. Therefore, the research presented here attempts to elucidate the regulatory elements responsible for the induction of the Rsv3-mediated extreme resistance response. Utilizing a comparative transcriptomic time series approach on Soybean mosaic virus-inoculated Rsv3 (resistant) and rsv3 (susceptible) soybean lines, this final study provides gene candidates putatively functioning in the regulation of biological pathways demonstrated to be crucial for Rsv3-mediated resistance. / Doctor of Philosophy / Soybeans are a crop of great economic importance, being a primary source of oil and protein for human and livestock consumption, respectively. Increasing demand for soybean calls for improvement in its production. An emerging field that has had tremendous impact on this endeavor is the field of functional genomics. Functional genomics approaches generate large-scale biological data that can aid in discerning how specific processes are regulated and controlled in an organism. The research presented in this work utilizes functional genomics approaches to elucidate the biological mechanisms underlying two economically important traits in soybean: seed phytic acid content and Soybean mosaic virus resistance. Phytic acid is a compound found in soybean seeds that causes nutrient deficiencies and phosphorus pollution. Soybeans with reduced to phytic acid content have been developed to mitigate these problems; they have poor seed germination and emergence. The studies in this work employ functional genomics approaches to compare unique sets of low and normal phytic acid soybeans to help establish the relationship between seed phytic acid content and seed performance. These studies resulted in new and promising hypotheses for future studies on investigating the low phytic acid trait. The final focus of this work used a functional genomics approach to discern the molecular mechanisms underlying a unique mode of resistance to Soybean mosaic virus. The study identified genes in soybean that are potentially critical to resistance against Soybean mosaic virus.

Le but de cette thèse est de préciser les mécanismes moléculaires agissant en aval du facteur de transcription CROWN ROOT LESS 1 (CRL1) qui régule la formation des racines coronaires (RC). Nous avons pu identifier dans un premier temps une nouvelle séquence d’ADN reconnue par CRL1 nommé CRL1-box différente de la LBD-box qui était le seul motif cis-régulateur précédemment décrit pour la famille des facteurs de transcription (FT) de type LATERAL ORGAN BOUNDARIES DOMAIN (LBD). Nous avons ensuite identifié un groupe de gènes régulés par CRL1, et avons montré l’implication de deux d’entre eux, OsROP et OsbHLH044, dans le développement des RC. OsbHLH044 est un facteur de transcription répresseur et semble être aussi impliqué dans la sénescence cellulaire ainsi que la réponse aux stress. Enfin, nous avons mis en évidence une cascade de régulation liant positivement CRL1 avec QUIESCENT-CENTER-SPECIFIC HOMEOBOX (QHB) un gène impliqué dans la différenciation et le maintien du centre quiescent via le facteur de transcription OsHOX14. En addition nous avons mis en évidence une boucle de rétroaction négative de QHB sur ses activateurs CRL1 et OsHOX14, qui pourrait être impliquée dans la structuration du primordia de racine coronaire. / The aim of this thesis is to specify the molecular mechanisms acting downstream of the CROWN ROOT LESS 1 transcription factor (CRL1) that regulates coronary root (CR) formation. We were able to identify at first a new CRL1 recognized DNA sequence named CRL1-box different from the LBD-box which was the only cis-regulatory motif previously described for the LATERAL ORGAN BOUNDARIES DOMAIN (LBD) transcription factor (TF) family. We then identified a group of genes regulated by CRL1, and showed the involvement of two of them, OsROP and OsbHLH044, in the development of CR. OsbHLH044 is a repressive transcription factor and appears to be also involved in cell senescence as well as stress response. Finally, we demonstrated a regulatory cascade linking CRL1 with QUIESCENT-CENTER-SPECIFICHOMEOBOX (QHB), a gene involved in the differentiation and maintenance of the quiescent center, via the OsHOX14 transcription factor. In addition we have demonstrated a negative feedback loop of QHB on its activators CRL1 and OsHOX14, which could be involved in structuring the coronary root primordia

<p>Specification and differentiation of a cell is accomplished by changing its gene expression profiles. These processes require temporally and spatially regulated transcription factors (TFs), to induce the genes that are necessary to a specific cell type. In each cell a set of TFs interact with each other or activate their targets; as development progresses, transcription factors receive regulatory inputs from other TFs and a complex gene regulatory network (GRN) is generated. Adding complexity, each TF can be regulated not only at the transcriptional level, but also by translational, and post-translational mechanisms. Thus, understanding a developmental process requires understanding the interactions between TFs, signaling molecules and target genes which establish the GRN.</p><p>In this thesis, two genes, FoxN2/3, a TF and FGFR1, a component of the FGF signaling pathway are investigated. FoxN2/3 and FGFR1 have different mechanisms that function in sea urchin development; FoxN2/3 regulates gene expression and FGFR1 changes phosphorylation of target proteins. However, their ultimate goals are the same: changing the state of an earlier GRN into the next GRN state. </p><p>First, we characterize FoxN2/3 in the primary mesenchyme cell (PMC) GRN. Expression of foxN2/3 begins in the descendants of micromeres at the early blastula stage; and then is lost from PMCs at the mesenchyme blastula stage. foxN2/3 expression then shifts to the secondary mesenchyme cells (SMCs) and later to the endoderm. Here we show that, Pmar1, Ets1 and Tbr are necessary for activation of foxN2/3 in the descendants of micromeres. The later endomesoderm expression is independent of the earlier expression of FoxN2/3 in micromeres and independent of signals from PMCs. FoxN2/3 is necessary for several steps in the formation of larval skeleton. A number of proteins are necessary for skeletogenesis, and early expression of at least several of these is dependent on FoxN2/3. Furthermore, knockdown (KD) of FoxN2/3 inhibits normal PMC ingression. PMCs lacking FoxN2/3 protein are unable to join the skeletogenic syncytium and they fail to repress the transfating of SMCs into the skeletogenic lineage. Thus, FoxN2/3 must be present for the PMC GRN to control normal ingression, expression of skeletal matrix genes, prevention of transfating, and control fusion of the PMC syncytium.</p><p>Second, we show that the FGF-FGFR1 signaling is required for the oral-aboral axis formation in the sea urchin embryos. Without FGFR1, nodal is induced in all of the cells at the early blastula stage and this ectopic expression of nodal requires active p38 MAP kinase. The loss of oral restriction of nodal expression results in the abnormal organization of PMCs and the larval skeleton; it also induces ectopic expression of oral-specific genes and represses aboral-specific genes. The abnormal oral-aboral axis formation also affected fgf and vegf expression patterns; normally these factors are expressed in two restricted areas of the ectoderm between the oral and the aboral side, but when FGFR1 is knocked down, Nodal expands, and in response the expression of the FGF and VEGF ligands expands, and this in turn affects the abnormal organization of larval skeleton.</p> / Dissertation

Fluctuations, or "noise", can play a key role in determining the behaviour of living systems. The molecular-level fluctuations that occur in genetic networks are of particular importance. Here, noisy gene expression can result in genetically identical cells displaying significant variation in phenotype, even in identical environments. This variation can act as a basis for natural selection and provide a fitness benefit to cell populations under stress. This thesis focuses on the development of new conceptual knowledge about how gene expression noise and gene network topology influence drug resistance, as well as new simulation techniques to better understand cell population dynamics. Network topology may at first seem disconnected from expression noise, but genes in a network regulate each other through their expression products. The topology of a genetic network can thus amplify or attenuate noisy inputs from the environment and influence the expression characteristics of genes serving as outputs to the network. The main body of the thesis consists of five chapters: 1. A published review article on the physical basis of cellular individuality. 2. A published article presenting a novel method for simulating the dynamics of cell populations. 3. A chapter on modeling and simulating replicative aging and competition using an object-oriented framework. 4. A published research article establishing that noise in gene expression can facilitate adaptation and drug resistance independent of mutation. 5. An article submitted for publication demonstrating that gene network topology can affect the development of drug resistance. These chapters are preceded by a comprehensive introduction that covers essential concepts and theories relevant to the work presented.

Fluctuations, or "noise", can play a key role in determining the behaviour of living systems. The molecular-level fluctuations that occur in genetic networks are of particular importance. Here, noisy gene expression can result in genetically identical cells displaying significant variation in phenotype, even in identical environments. This variation can act as a basis for natural selection and provide a fitness benefit to cell populations under stress. This thesis focuses on the development of new conceptual knowledge about how gene expression noise and gene network topology influence drug resistance, as well as new simulation techniques to better understand cell population dynamics. Network topology may at first seem disconnected from expression noise, but genes in a network regulate each other through their expression products. The topology of a genetic network can thus amplify or attenuate noisy inputs from the environment and influence the expression characteristics of genes serving as outputs to the network. The main body of the thesis consists of five chapters: 1. A published review article on the physical basis of cellular individuality. 2. A published article presenting a novel method for simulating the dynamics of cell populations. 3. A chapter on modeling and simulating replicative aging and competition using an object-oriented framework. 4. A published research article establishing that noise in gene expression can facilitate adaptation and drug resistance independent of mutation. 5. An article submitted for publication demonstrating that gene network topology can affect the development of drug resistance. These chapters are preceded by a comprehensive introduction that covers essential concepts and theories relevant to the work presented.

L'objet de cette thèse est l'utilisation de données transcriptomiques actuelles dans le but d'en inférer un réseau de régulation génique. Ces données sont souvent complexes, et en particulier des données d'interventions peuvent être présente. L'utilisation de la théorie de la causalité permet d'utiliser ces interventions afin d'obtenir des réseaux causaux acycliques. Je questionne la notion d'acyclicité, puis en m'appuyant sur cette théorie, je propose plusieurs algorithmes et/ou améliorations à des techniques actuelles permettant d'utiliser ce type de données particulières. / The purpose of this thesis is the use of current transcriptomic data in order to infer a gene regulatory network. These data are often complex, and in particular intervention data may be present. The use of causality theory makes it possible to use these interventions to obtain acyclic causal networks. I question the notion of acyclicity, then based on this theory, I propose several algorithms and / or improvements to current techniques to use this type of data.