Chicken intestinal development in health and disease : transcriptomic and modeling approaches

Research output: Thesisinternal PhD, WU

Abstract

Intestinal health is an important condition for sustainable animal production. Since it is known that there is significant variation in intestinal health and functionality, there is much to gain in this respect. However, to fully exploit the biological potential of the animal’s gastro-intestinal tract, the mechanism and regulation of major intestinal processes need to be unraveled first. In addition, identification of key components and processes involved in intestinal adaptation mechanisms may help to identify internal and external factors that influence the health and functioning of the gut. Improved knowledge in this area may contribute in defining rational strategies to improve sustainable animal production.
Traditionally research used reductionist approaches and focused on specific components or isolated processes related to intestinal functioning. However, the recent developments in the areas of genomics and computational sciences provide tools and methods that allow studying the system of the gut as a whole. In this thesis we have set first steps in the use of such Systems Biology approaches towards the identification of the key components and processes involved in intestinal functioning and health. We investigated molecular processes associated with gut development in chickens under two extreme contrasting conditions. We used an infection with Salmonella immediately after hatch and control animals to create the two contrasting phenotypic conditions. We used microarray-based genome-wide mRNA profiling to identify patterns of gene expression and cellular processes associated with each conditions. Comparisons between the two conditions and the application of modeling approaches revealed genes, groups of genes, molecular pathways, gene networks, and high level regulators of system behavior. We also used a mathematical modeling approach to describe the dynamics of cellular components of the immune system and their corresponding interactions under the same two contrasting conditions.
We identified different temporal gene expression profiles associated with morphological, functional and immunological processes. Several of these processes differed between the two contrasting conditions, whereas others were not affected be the experimental treatments. By inferring gene association networks, we observed that an infection with Salmonella considerably changes the behavior of intestinal tissue as well as the regulation of the underlying molecular processes. For each contrasting condition, we identified a specific set of potential high-level regulator genes (hubs). We hypothesize that these hubs are steering systems behavior. Bioinformatic analysis of the hubs suggested that the disturbance with Salmonella is associated with a shift from transcriptional regulation in the non-disturbed tissue to cell-cell communication in the disturbed tissue. Furthermore, the generated mathematical model describes the dynamics of the cellular components of the immune system as well as the dynamics of the invading pathogen well. The model was able to predict the cellular immune response of the host against an invading pathogen.
We developed basic knowledge of (molecular) processes that are associated with different physiological conditions of intestinal tissue and we acquired global views on adaptation mechanisms of the intestine, including the regulation thereof. This information can be used to formulate new hypotheses about behavioral aspects of the gut, for the discovery of new biological mechanisms, and ultimately for the development of tools and rational strategies to improve intestinal functionality and health, either via diet and/or the host genotype. Such developments are urgently required to diminish the incidence and impact of intestinal diseases in farm animal species and to reduce the use of antibiotics in animal husbandry.
 

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
Supervisors/Advisors
  • Smits, Mari, Promotor
  • Rebel, Annemarie, Co-promotor
Award date18 Jun 2012
Place of PublicationS.l.
Publisher
Print ISBNs9789462575325
Publication statusPublished - 2012

Fingerprint

transcriptomics
digestive system
chickens
taxonomic keys
Salmonella
sustainable agriculture
immune system
mathematical models
steering systems
gene expression
cell communication
genes
pathogens
animal husbandry
behavior change
regulator genes
digestive system diseases
farmed animal species
bioinformatics
infection

Keywords

  • fowls
  • intestines
  • biological development
  • gene expression
  • transcriptomics
  • animal health
  • poultry diseases
  • intestinal physiology
  • immunology
  • mathematical models

Cite this

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title = "Chicken intestinal development in health and disease : transcriptomic and modeling approaches",
abstract = "Intestinal health is an important condition for sustainable animal production. Since it is known that there is significant variation in intestinal health and functionality, there is much to gain in this respect. However, to fully exploit the biological potential of the animal’s gastro-intestinal tract, the mechanism and regulation of major intestinal processes need to be unraveled first. In addition, identification of key components and processes involved in intestinal adaptation mechanisms may help to identify internal and external factors that influence the health and functioning of the gut. Improved knowledge in this area may contribute in defining rational strategies to improve sustainable animal production. Traditionally research used reductionist approaches and focused on specific components or isolated processes related to intestinal functioning. However, the recent developments in the areas of genomics and computational sciences provide tools and methods that allow studying the system of the gut as a whole. In this thesis we have set first steps in the use of such Systems Biology approaches towards the identification of the key components and processes involved in intestinal functioning and health. We investigated molecular processes associated with gut development in chickens under two extreme contrasting conditions. We used an infection with Salmonella immediately after hatch and control animals to create the two contrasting phenotypic conditions. We used microarray-based genome-wide mRNA profiling to identify patterns of gene expression and cellular processes associated with each conditions. Comparisons between the two conditions and the application of modeling approaches revealed genes, groups of genes, molecular pathways, gene networks, and high level regulators of system behavior. We also used a mathematical modeling approach to describe the dynamics of cellular components of the immune system and their corresponding interactions under the same two contrasting conditions. We identified different temporal gene expression profiles associated with morphological, functional and immunological processes. Several of these processes differed between the two contrasting conditions, whereas others were not affected be the experimental treatments. By inferring gene association networks, we observed that an infection with Salmonella considerably changes the behavior of intestinal tissue as well as the regulation of the underlying molecular processes. For each contrasting condition, we identified a specific set of potential high-level regulator genes (hubs). We hypothesize that these hubs are steering systems behavior. Bioinformatic analysis of the hubs suggested that the disturbance with Salmonella is associated with a shift from transcriptional regulation in the non-disturbed tissue to cell-cell communication in the disturbed tissue. Furthermore, the generated mathematical model describes the dynamics of the cellular components of the immune system as well as the dynamics of the invading pathogen well. The model was able to predict the cellular immune response of the host against an invading pathogen. We developed basic knowledge of (molecular) processes that are associated with different physiological conditions of intestinal tissue and we acquired global views on adaptation mechanisms of the intestine, including the regulation thereof. This information can be used to formulate new hypotheses about behavioral aspects of the gut, for the discovery of new biological mechanisms, and ultimately for the development of tools and rational strategies to improve intestinal functionality and health, either via diet and/or the host genotype. Such developments are urgently required to diminish the incidence and impact of intestinal diseases in farm animal species and to reduce the use of antibiotics in animal husbandry.  ",
keywords = "fowls, intestines, biological development, gene expression, transcriptomics, animal health, poultry diseases, intestinal physiology, immunology, mathematical models, kippen, darmen, biologische ontwikkeling, genexpressie, transcriptomica, diergezondheid, pluimveeziekten, darmfysiologie, immunologie, wiskundige modellen",
author = "D.J. Schokker",
note = "WU thesis 5268",
year = "2012",
language = "English",
isbn = "9789462575325",
publisher = "s.n.",
school = "Wageningen University",

}

Chicken intestinal development in health and disease : transcriptomic and modeling approaches. / Schokker, D.J.

S.l. : s.n., 2012. 225 p.

Research output: Thesisinternal PhD, WU

TY - THES

T1 - Chicken intestinal development in health and disease : transcriptomic and modeling approaches

AU - Schokker, D.J.

N1 - WU thesis 5268

PY - 2012

Y1 - 2012

N2 - Intestinal health is an important condition for sustainable animal production. Since it is known that there is significant variation in intestinal health and functionality, there is much to gain in this respect. However, to fully exploit the biological potential of the animal’s gastro-intestinal tract, the mechanism and regulation of major intestinal processes need to be unraveled first. In addition, identification of key components and processes involved in intestinal adaptation mechanisms may help to identify internal and external factors that influence the health and functioning of the gut. Improved knowledge in this area may contribute in defining rational strategies to improve sustainable animal production. Traditionally research used reductionist approaches and focused on specific components or isolated processes related to intestinal functioning. However, the recent developments in the areas of genomics and computational sciences provide tools and methods that allow studying the system of the gut as a whole. In this thesis we have set first steps in the use of such Systems Biology approaches towards the identification of the key components and processes involved in intestinal functioning and health. We investigated molecular processes associated with gut development in chickens under two extreme contrasting conditions. We used an infection with Salmonella immediately after hatch and control animals to create the two contrasting phenotypic conditions. We used microarray-based genome-wide mRNA profiling to identify patterns of gene expression and cellular processes associated with each conditions. Comparisons between the two conditions and the application of modeling approaches revealed genes, groups of genes, molecular pathways, gene networks, and high level regulators of system behavior. We also used a mathematical modeling approach to describe the dynamics of cellular components of the immune system and their corresponding interactions under the same two contrasting conditions. We identified different temporal gene expression profiles associated with morphological, functional and immunological processes. Several of these processes differed between the two contrasting conditions, whereas others were not affected be the experimental treatments. By inferring gene association networks, we observed that an infection with Salmonella considerably changes the behavior of intestinal tissue as well as the regulation of the underlying molecular processes. For each contrasting condition, we identified a specific set of potential high-level regulator genes (hubs). We hypothesize that these hubs are steering systems behavior. Bioinformatic analysis of the hubs suggested that the disturbance with Salmonella is associated with a shift from transcriptional regulation in the non-disturbed tissue to cell-cell communication in the disturbed tissue. Furthermore, the generated mathematical model describes the dynamics of the cellular components of the immune system as well as the dynamics of the invading pathogen well. The model was able to predict the cellular immune response of the host against an invading pathogen. We developed basic knowledge of (molecular) processes that are associated with different physiological conditions of intestinal tissue and we acquired global views on adaptation mechanisms of the intestine, including the regulation thereof. This information can be used to formulate new hypotheses about behavioral aspects of the gut, for the discovery of new biological mechanisms, and ultimately for the development of tools and rational strategies to improve intestinal functionality and health, either via diet and/or the host genotype. Such developments are urgently required to diminish the incidence and impact of intestinal diseases in farm animal species and to reduce the use of antibiotics in animal husbandry.  

AB - Intestinal health is an important condition for sustainable animal production. Since it is known that there is significant variation in intestinal health and functionality, there is much to gain in this respect. However, to fully exploit the biological potential of the animal’s gastro-intestinal tract, the mechanism and regulation of major intestinal processes need to be unraveled first. In addition, identification of key components and processes involved in intestinal adaptation mechanisms may help to identify internal and external factors that influence the health and functioning of the gut. Improved knowledge in this area may contribute in defining rational strategies to improve sustainable animal production. Traditionally research used reductionist approaches and focused on specific components or isolated processes related to intestinal functioning. However, the recent developments in the areas of genomics and computational sciences provide tools and methods that allow studying the system of the gut as a whole. In this thesis we have set first steps in the use of such Systems Biology approaches towards the identification of the key components and processes involved in intestinal functioning and health. We investigated molecular processes associated with gut development in chickens under two extreme contrasting conditions. We used an infection with Salmonella immediately after hatch and control animals to create the two contrasting phenotypic conditions. We used microarray-based genome-wide mRNA profiling to identify patterns of gene expression and cellular processes associated with each conditions. Comparisons between the two conditions and the application of modeling approaches revealed genes, groups of genes, molecular pathways, gene networks, and high level regulators of system behavior. We also used a mathematical modeling approach to describe the dynamics of cellular components of the immune system and their corresponding interactions under the same two contrasting conditions. We identified different temporal gene expression profiles associated with morphological, functional and immunological processes. Several of these processes differed between the two contrasting conditions, whereas others were not affected be the experimental treatments. By inferring gene association networks, we observed that an infection with Salmonella considerably changes the behavior of intestinal tissue as well as the regulation of the underlying molecular processes. For each contrasting condition, we identified a specific set of potential high-level regulator genes (hubs). We hypothesize that these hubs are steering systems behavior. Bioinformatic analysis of the hubs suggested that the disturbance with Salmonella is associated with a shift from transcriptional regulation in the non-disturbed tissue to cell-cell communication in the disturbed tissue. Furthermore, the generated mathematical model describes the dynamics of the cellular components of the immune system as well as the dynamics of the invading pathogen well. The model was able to predict the cellular immune response of the host against an invading pathogen. We developed basic knowledge of (molecular) processes that are associated with different physiological conditions of intestinal tissue and we acquired global views on adaptation mechanisms of the intestine, including the regulation thereof. This information can be used to formulate new hypotheses about behavioral aspects of the gut, for the discovery of new biological mechanisms, and ultimately for the development of tools and rational strategies to improve intestinal functionality and health, either via diet and/or the host genotype. Such developments are urgently required to diminish the incidence and impact of intestinal diseases in farm animal species and to reduce the use of antibiotics in animal husbandry.  

KW - fowls

KW - intestines

KW - biological development

KW - gene expression

KW - transcriptomics

KW - animal health

KW - poultry diseases

KW - intestinal physiology

KW - immunology

KW - mathematical models

KW - kippen

KW - darmen

KW - biologische ontwikkeling

KW - genexpressie

KW - transcriptomica

KW - diergezondheid

KW - pluimveeziekten

KW - darmfysiologie

KW - immunologie

KW - wiskundige modellen

M3 - internal PhD, WU

SN - 9789462575325

PB - s.n.

CY - S.l.

ER -