Dissertations, Theses, and Capstone Projects

Date of Degree

9-2024

Document Type

Dissertation

Degree Name

Ph.D.

Program

Biology

Advisor

Anuradha Janakirman

Committee Members

Stefan Pukatzki

Christine Li

Haiping Cheng

David Dubnau

Subject Categories

Cell Biology | Life Sciences | Microbiology

Abstract

E. coli cell envelope is a complex multilayered structure that serves as the initial line of defense against harmful environments and toxic substances like antibiotics. This structure is composed of an outer and an inner membrane separated by the periplasmic space and a thin peptidoglycan cell wall. These lipid-rich membranes contain nearly 30% of the cell's proteome and several of these membrane proteins participate in envelope biogenesis functions. Membrane homeostasis is therefore essential for cell functionality and survival and is accomplished by coordinating the synthesis of membrane components such as phospholipids and lipopolysaccharides with cell growth and division. Each lipid component requires a continuous supply of fatty acids, which are mostly derived from de novo synthesis. Given the energetic cost associated with fatty acid biosynthesis (FAB), this process is tightly regulated at different levels to ensure the systematic distribution of lipids between these processes. Although significant advancements have been made in comprehending the regulatory mechanisms of FAB in specific conditions, a comprehensive model that encompasses all aspects of regulation and the consequence of its dysregulation remains to be developed. Over a third of membrane proteins have unknown or poorly understood functions, and many factors that regulate important aspects of lipid homeostasis likely remain unknown. In this thesis, I describe the molecular characterization of two such proteins and their likely roles in regulating lipid pathways.

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