Dissertations, Theses, and Capstone Projects

Date of Degree

9-2026

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy

Program

Biology

Advisor

Mandë Holford

Committee Members

Jayne Raper

Weigang Qiu

John Dennehy

Li Zhao

Subject Categories

Bioinformatics | Biology | Immunity

Keywords

Venom, Micropeptides, Immunology, Nextflow, RNAseq, Cephalopod

Abstract

Arms-race interactions such as host-pathogen and predator-prey interactions are powerful drivers of rapid molecular evolution. Many of the novel transcripts arising from these dynamics remain unannotated and poorly characterized, limiting our understanding of these biological processes. While many of these genetic changes may be inconsequential or even damaging, some result in novel compounds that are beneficial in arms-race interactions. The central goal of my dissertation is to identify and characterize rapidly evolving, previously unannotated transcripts that contribute to arms-race interactions, using two distinct but conceptually linked systems: the innate immune response and cephalopod venom evolution. In innate immunity, research has historically focused on conserved proteins, leaving the role of small peptides ≤100 amino acids (micropeptides) largely unexplored. Recent research has revealed functional micropeptides translated from short open reading frames (sORFs) of immune-related transcripts previously thought to be non-coding. This raises the possibility that a substantial and uncharacterized class of rapidly evolving immune effectors exists, with important consequences for host defense and immune regulation. Similarly, cephalopod venoms represent an understudied example of rapid evolutionary innovation. Previous research has shown that several species of cephalopods express proteins in their posterior salivary glands that are toxic to their prey. However, most of the venom gland transcriptome remains unannotated. This knowledge gap limits our understanding of how venom systems diversify and how new toxin genes emerge and evolve. To address these questions, my dissertation applies an integrated -omic approach combining RNA-seq and proteomics to systematically identify novel transcripts in immune-related cells and the posterior salivary glands of multiple coleoid cephalopod species (squid, octopus, and cuttlefish).  This approach is designed to uncover novel genes that are missed by standard annotation pipelines and to prioritize transcripts for further experimental validation.

Thesis_SupplementaryFile1.xlsx (1639 kB)
Immune micropeptides

Thesis_supplementaryFile2.xlsx (115621 kB)
Cephalopods

Thesis_supplementary file 3.docx (192 kB)
deca-ctx alignments

This work is embargoed and will be available for download on Thursday, September 30, 2027

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