Publication Date

8-2020

Date of Final Oral Examination (Defense)

8-12-2020

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biology

Supervisory Committee Chair

Allan Albig, Ph.D.

Supervisory Committee Member

Julie Thom Oxford, Ph.D.

Supervisory Committee Member

Kenneth A. Cornell, Ph.D.

Supervisory Committee Member

Richard S. Beard, Ph.D.

Abstract

The Notch signaling pathway is a core component of multicellularity; enabling cells to directly communicate with both their neighbors and the surrounding microenvironment. These signals are translated directly through the Notch proteins, where a fragment of Notch transitions into the nucleus to act as a co-transcription factor, setting into motion a host of physiological responses. Commonly involved in pathways that define a cell’s identity and fate decisions, what appears to be a simplistic pathway instead exists in a state of high-tunability and strict control. Missteps in this pathway are generally embryonically lethal or lead to a suite of congenital disorders and cancers. Therefore, it’s pertinent to understand the mechanisms of Notch that provide its flexibility and pleiotropic outcomes. One such property is its ability to homodimerize on DNA while within its transcriptional activation complex, resulting in an enhanced transcriptional signal of a select pool of Notch target genes. This dissertation reviews the general mechanics behind Notch signaling, discusses how the field of Notch dimerization came to be and where it stands currently, and finally, details my contributions to the understanding of this regulatory mechanism. Despite Notch’s ubiquitous function in metazoan life, there are still many mysteries behind this signaling pathway. The work detailed here describes my time spent as a basic science researcher, where my findings contribute a couple of puzzle pieces to the expansive Notch signaling field.

DOI

10.18122/td/1738/boisestate

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