Publication Date
5-2024
Date of Final Oral Examination (Defense)
3-8-2024
Type of Culminating Activity
Dissertation
Degree Title
Doctor of Philosophy in Biomolecular Sciences
Department Filter
Biology
Department
Biological Sciences
Supervisory Committee Chair
Allan Albig, Ph.D.
Supervisory Committee Member
Cheryl Jorcyk, Ph.D.
Supervisory Committee Member
Daniel Fologea, Ph.D.
Supervisory Committee Member
Henry Charlier, Ph.D.
Abstract
Cellular signaling pathways are the main method of communication between cells throughout the body. Of the many complex signaling pathways, the Notch signaling pathway is an ancient, highly conserved pathway critical to most animal life. This pathway is not only able to respond to juxtracrine signals from neighboring cells, but also acts as a microenvironment sensor, allowing cells to react to a variety of situations. Thus, understanding the mechanisms behind the regulation of Notch signaling is crucial to improving our basic understanding of Notch in cell biology and development. This dissertation introduces two previously undescribed non-canonical regulatory mechanisms of the Notch signaling pathway: heterodimerization and biomolecular condensate formation. Although Notch1 homodimerization has been characterized, the details of interaction between the four Notch isoforms have yet to be fully explored. We found that not only do all four Notches heterodimerize, but that these head-to-head dimer interactions are transcriptionally relevant. The second non-canonical mechanism, LLPS condensate formation, has only begun to be discovered, with little research exploring Notch1 localization into non-membrane bound organelles. We have found that each Notch isoform differentially forms these biomolecular condensates, leaving much to be uncovered about their overall function. My work, as well as that of my colleagues, has begun to characterize an entirely new understanding of how Notch signaling works. Once thought to be a straightforward pathway, my contributions as a basic scientist have introduced a layer of complexity that will help to understand how Notch can perform a variety of functions.
DOI
https://doi.org/10.18122/td.2212.boisestate
Recommended Citation
Gazdik, Tana Ranae, "A Journey to the Center of the Cell: The Characterization of Novel Non-Canonical Mechanisms of Notch Signaling" (2024). Boise State University Theses and Dissertations. 2212.
https://doi.org/10.18122/td.2212.boisestate
