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ErikaLEnglish_Dissertation_finaldraft_21MAY26
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Dissertation
BRAIN PEPTIDOGLYCAN DETECTION AND SIGNALING LINKED TO SLEEP
Doctor of Philosophy (PhD), Washington State University
2025
Abstract
Sleep regulation includes a range of inputs and associated mechanisms which come together to influence how and when sleep manifests locally within cellular networks and globally over time. Regulatory components include genetic factors and small molecules, which have local influence on various cell types and associated networks, and the environmental fluctuations sensed over time which guide sleep regulatory circuits, such as seasonal changes in light and temperature. Together, these inputs and the outputs to which they are linked, are coordinated to maintain sleep. The holobiont condition is important for balanced organismal health including guiding sleep physiology. Resident microbes and the products they produce, including constitutively released bacterial cell wall fragments, have a role in host sleep regulation. Bacterial cell wall peptidoglycan and the smaller muropeptide constituents are sleep promoting compounds. Peptidoglycans are in brain in varying amounts; fluctuations occur with time-of-day and after sleep loss with brain area specificity. The peptidoglycan receptor, peptidoglycan recognition protein 1 (Pglyrp1), is important for guiding brain peptidoglycan levels and responses to sleep loss. Pglyrp1 guides sleep rebound amount and the molecular gene expression changes for genes previously linked to cytokine, growth factor, and immune functions following sleep loss. Together, brain peptidoglycan, its receptors, and the host signaling pathways they influence provide a tonic stimulus to support bi-directional communication involved in sleep regulatory function at the local and global scales.
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Details
- Title
- BRAIN PEPTIDOGLYCAN DETECTION AND SIGNALING LINKED TO SLEEP
- Creators
- Erika English
- Contributors
- James M. Krueger (Advisor)Franck Carbonero (Committee Member)Alan Goodman (Committee Member)Michael Konkel (Committee Member)Jon Oatley (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Molecular Biosciences
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 201
- Identifiers
- 99901393403201842
- Language
- English
- Resource Type
- Dissertation