Microbiome and Epigenetics: Two Keys to the development of Personalized Medicine
Open Access
- Author:
- Malys, Tyler
- Graduate Program:
- Integrative Biosciences
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- October 16, 2014
- Committee Members:
- Cooduvalli S Shashikant, Dissertation Advisor/Co-Advisor
Ross Cameron Hardison, Committee Member
Michael Mugo Mwangi, Committee Member
Matam Vijay Kumar, Committee Member
Peter John Hudson, Special Member - Keywords:
- Microbiome
Epigenetics
Personalized Medicine
Agriculture
Pathogen Identification
Erythropoiesis
Pakistan
Gene Expression - Abstract:
- This dissertation has two parts: first describes the analysis of microbiomes of the lower respiratory tract of healthy and diseased chickens. The second describes the epigenetic landscape that determines the gene transcription levels in the erythroid differentiation model. Multicellular animals are complex machines and can no longer be thought of as stand alone organisms. Animals host microbial communities termed microbiomes, which play vital roles in many aspects of an animals life including immune function and nutrient processing. Animal physiology and habits have been shown to affect resident microbiome composition, which in turn affect animal physiology. Understanding host microbe interactions and their ramifications is thus essential in my pursuit to understand human health. Further complicating matters, each microbiome interacts with only a subset of host cell types. Nearly every host cell contains identical DNA yet express radically different phenotypes. These differences in phenotype are brought about by epigenetic effect. Epigenetic factors represent heritable changes, which are not apparent in DNA sequence alone. They include items such as histone modifications, transcription factors and DNAse hypersensitive sites. Epigenetics vary amongst individuals but also amongst cell types within individuals. Understanding epigenetic regulation of gene transcription is essential to understanding human health and has gained much interest in the development of personalized medicine. I conducted fundamental research aimed at advancing both the understanding of resident microbiome and also epigenetic gene regulation. Microbiome studies were conducted in Chickens from Pakistan with the primary goal of identifying potentially novel emerging infectious diseases. I also studied epigenetic gene regulation in an in vitro model system for erythroid maturation. I found that the lower respiratory microbiome of healthy chickens was dominated by relatively few bacterial taxa. Moreover the microbiome of healthy chickens varied with respect to the environment. I was also able to identify differences in microbiome composition between healthy and diseased birds, suggesting the discovery of potential novel pathogens representing emerging infectious disease in the region. In my model system for erythroid maturation I found epigenetic landscape near the transcription start site (TSS) to be sufficient to predict a gene as actively transcribed or silent. Moreover, I was able to relate change in epigenetic landscape with change in gene transcription level in cases of extreme transcription level change. Overall, these results indicated epigenetic landscape near the TSS sets a gene as either permissive or non permissive with respect to transcription.