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Principal Investigator: Maxwell Clark Coyle
Organization: HARVARD UNIVERSITY
Fiscal Year: 2024
Award: $73,408
Funding agency: National Institute of General Medical Sciences
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.
Terms: <ATP-protein phosphotransferase><Action Potentials><Advisory Committees><Alleles><Allelomorphs><Anemone><Animals><Behavior><Behavioral><Bio-Informatics><Biochemical><Biochemistry><Bioinformatics><Biological Chemistry><Biology><Bionomics><Cell Body><Cell Communication><Cell Communication and Signaling><Cell Differentiation><Cell Differentiation process><Cell Function><Cell Interaction><Cell Physiology><Cell Process><Cell Signaling><Cell-to-Cell Interaction><Cells><Cellular Function><Cellular Physiology><Cellular Process><Cellular biology><Cellularity><Chemotaxis><Cloning><Collaborations><Communication><Complex><Cues><Data><Decision Making><Ecology><Electrophysiology><Electrophysiology (science)><Engineering><Environment><Esthesia><Eukaryota><Eukaryote><Event><Evolution><Family><Foundations><Gene Family><Gene Transfer Techniques><GeneHomolog><Genetic><Genetic Engineering><Genetic Engineering Biotechnology><Genetic Engineering Molecular Biology><Genome><Habitats><Homolog><Homologous Gene><Homologue><Intracellular Communication and Signaling><Intracellular Second Messenger><Kinase Family Gene><Knock-out><Knockout><Learning><Liquid substance><Measures><Mediating><Microfluidics><Microscopy><Modeling><Molecular><Nervous System><Neural Receptors><Neurologic Body System><Neurologic Organ System><Neurophysiology / Electrophysiology><Neuroreceptors><O element><O2 element><Octopus><Organism><Output><Oxygen><Physiologic><Physiological><Physiology><Preparation><Property><Protein Kinase><Receptor Protein><Recombinant DNA Technology><Second Messenger Systems><Second Messengers><Sensation><Sensory><Sensory Receptors><Shark><Signal Transduction><Signal Transduction Systems><Signaling><Stimulus><Subcellular Process><Swimming><System><Task Forces><Testing><Transgenesis><advisory team><behavior response><behavioral response><bio-informatics tool><bioinformatics tool><biological signal transduction><cell behavior><cell biology><cellular behavior><cellular differentiation><delta pH><deltapH><desensitization><electrical property><electrophysiological><fluid><genetically engineered><genome editing><genomic editing><global gene expression><global transcription profile><glycogen synthase a kinase><hydroxyalkyl protein kinase><innovate><innovation><innovative><interest><liquid><living system><model organism><novel><pH gradient><patch clamp><perceptual stimulus><pharmacologic><phosphorylase b kinase kinase><physicochemical phenomena related to the senses><preparations><receptor><response><sensory integration><sensory mechanism><sensory stimulus><sensory system><signal transduction second messengers><skills><small molecule><tool><transcriptome><voltage><µfluidic>