Interdisciplinary Initiatives Program Round 12 - 2024
Project Investigators:
Ayelet Voskoboynik, Biology
Julia Salzman, Biomedical Data Science and Biochemistry
Abstract:
The intricate interplay between host and pathogen has driven the evolution of diverse immune systems across the animal kingdom. While the adaptive immune system in jawed vertebrates confers specific and long-lasting immunity, invertebrates predominantly rely on the innate immune system for pathogen defense. However, the presence of adaptive immune system-like elements in invertebrates remains an intriguing and underexplored question.
This study proposes a collaborative investigation utilizing Botryllus schlosseri, the closest living invertebrate relative to humans, to explore the potential presence of adaptive immune system relics. Botryllus offers unique advantages due to its complex colonial life cycle and previously characterized self-non-self-recognition mechanisms. We hypothesize that ancestral adaptive immune system-like genes might have diverged significantly throughout millions of years of evolution, making them challenging to identify in Botryllus using conventional methods.
To address this challenge, we will apply SPLASH (Statistically Primary aLignment Agnostic Sequence Homing), a novel method developed by the Salzman lab, to single-cell RNA sequencing (scRNAseq) data from Botryllus blood cells. This approach will identify genes exhibiting extensive recombination, a hallmark of Ig and TCR genes in the adaptive immune system. Candidate genes identified by SPLASH will be mapped to the Botryllus genome to assess their linkage, proximity to the Botryllus Histocompatibility Factor (BHF) region, and synteny with the human MHC locus. This analysis will provide insights into potential conservation and divergence of immune system architecture across species. We will predict the 3D structures of the most promising candidate genes using AlphaFold to infer their potential functions and similarity to known immune receptors and analyze the expression patterns of these genes across various conditions, including infection with marine pathogens and allogeneic transplant rejection, to understand their potential role in Botryllus immune responses.
By integrating these analyses, we aim to: Uncover potential adaptive immune system relics in Botryllus, and advance evolutionary understanding of immune system evolution. This collaborative research holds significant potential to revolutionize our understanding of the adaptive immune system origin and pave the way for future discoveries in the field of comparative immunology and therapeutic development.
