Chemical and Biomolecular Engineering, Department of

 

First Advisor

RajibSaha

Committee Members

Rajib Saha, Vitali Alexandrov, Yaşar Demirel

Date of this Version

7-2024

Document Type

Thesis

Citation

A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science

Major: Chemical Engineering

Under the supervision of Professor Rajib Saha

Lincoln, Nebraska, July 2024

Comments

Copyright 2024, Abraham Boluwatife Osinuga. Used by permission

Abstract

Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. In this study, we explore its de novo biosynthesis and homeostasis in Arabidopsis thaliana cell cultures, shedding light on fundamental metabolic mechanisms. Employing 15N isotope labeling and quantitative dynamic modeling approach, we obtained data with notable variations and developed a regularized and constraint-based Dynamic Metabolic Flux Analysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase (LCBK) to be critical for maintaining sphingolipid homeostasis. In silico disruptions in these enzymes were found to affect cellular viability and increase the potential for programmed cell death (PCD). Despite challenges posed by data variability, this work enhances our understanding of sphingolipid metabolism and demonstrates the utility of dynamic modeling in analyzing complex metabolic pathways. Collectively, this research exemplifies the profound potential of systems biology in unraveling intricate metabolic pathway regulations with broad-ranging implications.

Advisor: Rajib Saha

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