Exploiting unicellular animal relatives to understand the evolution of sensory systems - PROJECT SUMMARY Multicellular nervous systems allow animals to sense and respond to their specific environments. Yet animals evolved from unicellular eukaryotes, in which a single cell must carry out signal transduction from sensation to behavior. Therefore, understanding how unicellular eukaryotes sense and transduce important environmental cues into specific behaviors can reveal foundational principles of cellular signaling upon which animal multicellular sensory systems are built. Choanoflagellates (choanos) are a diverse group of micro-eukaryotes that are the closest living relatives of animals. Choanos are bacterivorous, requiring them to sense and navigate changes in pH, oxygen, and metabolites within their environment to find bacterial prey. Choanos have diversified to occupy a range of aquatic habitats, providing an opportunity to understand how their sensory mechanisms evolve to meet the demands of diverse ecologies. Furthermore, while typically unicellular, some choanos also have simple multicellular forms. Here, I propose to investigate how unicellular organisms detect and respond to a range of environmental cues and how these sensory systems evolve in conjunction with diverse ecologies and the innovation of multicellularity. This project builds on my expertise in bioinformatics, microscopy, and choano genetics, while learning new skills in electrophysiology and the biochemistry of sensory systems in the lab of Dr. Nicholas Bellono (Harvard MCB), who has pioneered physiological studies of sensory systems in non-traditional model organisms such as sharks, octopuses, anemones, and more. I plan to uncover fundamental principles of sensory biology and signal transduction, as well as to help reconstruct the types of sensory systems found in the unicellular ancestors of animals. I will be aided by an interdisciplinary advisory team, including my co-sponsor Dr. Richard Losick (Harvard MCB), a rigorous molecular biologist who will push me towards a mechanistic understanding of my system. I will also collaborate with Dr. Agnese Seminara (Univeristy of Genoa), a biophysicist specializing in fluid dynamics and decision-making, as well as Dr. Ryan Nett (Harvard MCB), an expert on small molecule isolation and characterization. I will characterize choano behavior and physiology in response to pH, oxygen, and bacterial metabolites, using electrophysiology and genetically encoded Ca2+ indicator strains (Aim 1). I will identify the receptors mediating these sensory systems and use gene family evolution analyses to explore how these choano receptor families have diversified in response to divergent aquatic environments (Aim 2). Finally, I will explore how choanos integrate multiple simultaneous sensory cues (e.g. pH and oxygen) in both their unicellular and multicellular forms to understand how multicellular evolution drives the innovation and integration of sensory systems, essential for animal origins.
