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Regulation of Lipid-Droplet Alterations Upon Infection (Molecular Mechanisms at Play)

McKinzie, Sierra Rose (2022) Regulation of Lipid-Droplet Alterations Upon Infection (Molecular Mechanisms at Play). Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

The immune response is an energy intensive process. To fuel the response, organisms must effectively utilize limited resources. Consequently, fueling one physiological response can diminish resource allocation towards another. Both fertility and immunity utilize energy stores in the form of lipids to meet their energy demands. Studies in model organisms and in nature have suggested that fertility and immunity are mutually antagonistic. However, the molecular mechanisms underlying this relationship remain poorly understood. Immune response to acute pathogenic infections depends on lipid mobilization for energy. Similarly, reproduction is also highly dependent on lipid resources. Here, we have used the model organism, Caenorhabditis elegans, to address the role of lipid metabolism in the immunity-fertility relationship. These studies are based on the discoveries in the Ghazi lab that a transcription elongation and splicing factor, TCER-1, promotes fertility and represses immunity likely by modulating lipid-metabolic genes and processes. To understand how lipid stores are impacted by infection, wild-type worms expressing the lipid droplet resident protein PLIN-1, tagged with GFP (PLIN-1::GFP), were imaged after pathogenic exposure. These experiments revealed that pathogenic infection decreases individual lipid droplet size and total volume compared. This finding agrees with previous work and establishes this method as suitable for future studies investigating the impact of TCER-1 and infection on lipid droplets. Furthermore, we evaluated the impact of the loss of function of TCER-1-target lipases, lipl-1 and lipl-2, on immune resilience. In nutrient-poor conditions, lipase-like (lipl) genes are a critical factor in the mobilization of lipids. However, their role in infection response has not been studied. Preliminary data from the Ghazi lab suggests that TCER-1 represses lipl-1 and lipl-2 to inhibit immunity. Our experiments here showed that within the C. elegans immune system, both lipl-1 and lipl-2 are necessary for immune resilience. These findings suggest lipid metabolism is a crucial target of TCER-1 and verify a new method to investigate its effect on lipid droplet characteristics. They will contribute towards an increased understanding of the dynamics of immune responses and are of particular public health relevance as the COVID19 pandemic unfolds.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
McKinzie, Sierra Rosesrm121@pitt.edusrm1210000-0001-8424-478X
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorGhazi, Arjumandghazia@pitt.edughazia
Committee MemberAmrit, Francisfrancisamrit@pitt.edufrancisamrit
Committee MemberDemirci, Yesimfyd1@pitt.edufyd1
Committee MemberRoman, Bethromanb@pitt.eduromanb
Date: 6 January 2022
Date Type: Publication
Defense Date: 16 December 2021
Approval Date: 6 January 2022
Submission Date: 22 December 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 42
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Immunity, lipid metabolism, fat storage, Caenorhabditis elegans, stress resistance
Date Deposited: 06 Jan 2022 20:15
Last Modified: 06 Jan 2022 20:15
URI: http://d-scholarship.pitt.edu/id/eprint/42139

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