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Molecular Mechanisms Controlling Immunity, Fertility, and Longevity

Naim, Nikki (2022) Molecular Mechanisms Controlling Immunity, Fertility, and Longevity. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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[img] Microsoft Excel (Supplementary File 1. smRNAseq of tcer-1 mutants)
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[img] Microsoft Excel (Supplementary File 2. mRNAseq of tcer-1 mutants)
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[img] Microsoft Excel (Supplementary File 3. Overlap analysis of smRNAseq and mRNAseq datasets)
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[img] Microsoft Excel (Supplementary File 4. Selection of smRNA candidates through which TCER-1 might suppress immunity)
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[img] Microsoft Excel (Supplementary File 5. Fluorescence scoring of QDPR-1-GFP strains)
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[img] Microsoft Excel (Supplementary Table 2.1 RNA-seq results of nhr-49;glp-1 and glp-1 strains)
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[img] Microsoft Excel (Supplementary Table 3.1 (a-e) Effect of transgenic TCER-1 expression driven by tissue-specific promoters on lifespan of different strains on E. coli OP50 diet)
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All organisms must balance their cellular resources to invest in life processes such as reproduction, immunity, and longevity to persist as a species. For this reason, animal fertility often wanes during an immune response and vice versa. Increased reproductive activity has also been associated with reduced lifespan in many species. Studies suggest that animals possess genetic mechanisms which coordinate such life history traits, yet, the molecular mechanisms underlying these reproduction-immunity-longevity (RIL) relationships remain largely unexplored. The nematode Caenorhabditis elegans is a model organism which has long been used to characterize conserved genetic regulators of reproduction, immunity, and longevity. Work from our laboratory, which identified that two C. elegans transcription factors, NHR-49 and TCER-1, impact RIL processes therefore opened avenues to investigate RIL coordination in animals. NHR-49, proposed functional homolog of the vertebrate protein, PPARα, is a nuclear hormone receptor noted to promote lifespan and lipid homeostasis. TCER-1, shown to promote lifespan and fertility, is the C. elegans homolog of the human transcription and elongation splicing factor, TCERG1. My work exploring RIL coordination by these factors has shown that NHR-49 promotes both immune resistance and longevity but acts in distinct tissues to regulate these traits. Studying TCER-1 revealed that the protein additionally suppresses immunity while promoting fertility, supporting previous hypotheses that TCER-1 enacts RIL tradeoffs. Further characterization based on these findings showed that TCER-1 likely promotes small RNA production to suppress immunity in fertile animals. The results of these projects therefore describe (a) new functions of well-studied proteins in the RIL dialogue, (b) new mechanisms of context-dependent regulation by these genes, and (c) new effectors of these pathways. These findings support emerging concepts in aging biology that genetic mechanisms which control reproduction, immunity, and longevity are both distinct and interconnected. For humans, these studies may uncover what immune mechanisms are suppressed in fertility and how to target drugs that improve health as well as lifespan.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Naim, Nikkinin27@pitt.edunin270000-0002-2005-7202
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberCarlson, Anneacarlson@pitt.edu0000-0003-2724-1325
Committee MemberLamitina, Toddstl52@pitt.edu0000-0001-7332-9075
Committee MemberPandey, Udaiudai@pitt.edu0000-0002-6267-0179
Committee MemberTsang, Michaeltsang@pitt.edu0000-0001-7123-0063
Committee ChairYanowitz, Judithjly23@pitt.edu0000-0001-6886-8787
Thesis AdvisorGhazi, Arjumandghazia@pitt.edu0000-0002-5859-4206
Date: 7 March 2022
Date Type: Publication
Defense Date: 16 February 2022
Approval Date: 7 March 2022
Submission Date: 2 March 2022
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 261
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Genetics and Developmental Biology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Aging, Longevity, Immunity, Fertility, Reproduction, C. elegans
Date Deposited: 08 Mar 2022 04:22
Last Modified: 07 Mar 2024 06:15


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