Application of Molecular Evolutionary Principles to Functional Enhancement of a Proto-Synapse

This project seeks to enhance and explore synaptic function by replacing specific synaptic genes with their deep ancestral homologues. The work draws upon the rich and relatively unexplored diversity of molecular machines within the kingdom of the Protista, precursors to animals present on the earth for about 1.2 billion years. Present within these organisms are genes with deep homologies to synaptic genes that function in proto-synaptic structures at the base of the animal kingdom. However, animals drew upon only a small fraction of this enormously diverse gene set. We propose that the highly diverse set of genes in Protista (single cell eukaryotes) with homology to modern synaptic genes, but lost in the animal lineage, offer a means to enhance synaptic function and/or serve as heuristic tools to probe synaptic function. Many of the most significant advances in biology have utilized genes from distant organisms, e.g green fluorescent protein from the jellyfish Aequorea Victoria, channel rhodopsin for optogenetics from green algae Chlamydomonas reinhardtii, and Cas9, Cas12 and Cas13 endonucleases for CRISPR from bacteria and archaea.