Molecular tuning of sensory systems in octopus - All organisms sense and adapt to changes in their environment. Alterations in organismal state can lead to
epigenetic changes that dramatically influence how an animal interacts with its environment. How organisms
acutely alter sensation based on their behavioral state is not well understood. Octopuses are incredible sensory
specialists that use ‘taste by touch’ chemotactile sensation to interact with their environment. This sensory
system is mediated by specialized chemotactile receptors (CRs) that detect poorly soluble molecules, such as
those secreted by prey. If prey is unavailable for prolonged periods, do octopuses adapt to become more
sensitive predators? One mechanism octopus might deploy to adapt is epigenetic adenosine to inosine (A-to-I)
editing. Octopuses readily diversify their proteomes through editing mRNA transcripts by swapping adenosine
for inosine, which is interpreted as a guanosine during translation. This process allows a single gene to produce
multiple different translated proteins with potentially new functions. I will test the hypothesis that manipulation of
organismal state biases preferential A-to-I editing to transiently alter protein sequence and function and modulate
the detection of environmental signals most salient to the specific organismal state. Such a mechanism could
tune the unique octopus chemotactile sensory system to be more sensitive to prey molecules when hungry. This
project will utilize a multifaceted approach spanning from RNA biology to animal behavior, providing me with
ample opportunity to learn new concepts, techniques, and establish an independent trajectory following my
postdoctoral training. My diverse advisory team will provide expert guidance in cell physiology (Nicholas Bellono),
RNA biology (Amy Lee), channel structure-function (Ryan Hibbs), and animal behavior (Venkatesh Murthy). In
these studies, I will use molecular and biochemical approaches to identify which CRs are targets of RNA editing
or are preferentially translated in response to distinct organismal states, such as starved versus fed (Aim 1). Our
preliminary data demonstrate that octopuses edit protein-coding regions of CRs during periods of starvation.
After identifying the spectrum of CR variants, I will characterize the biophysical properties of recoded CRs against
unedited CRs to determine the functional consequences of state-dependent editing (Aim 2). I will focus my
analysis on ligand sensitivity and ion permeation, which could account for increased sensitivity to prey molecules
or altered neural signaling. Finally, I will leverage these discoveries to understand how the acute editing of
individual proteins affects adaptive organismal sensation (Aim 3). I will carry out behavioral assays to test
whether specific changes in protein function correlate with altered behavior across starved and fed octopuses.
For example, if starvation-induced RNA editing of CRs alters sensitivity to prey molecules to enhance prey
detection, I will test the threshold for chemically induced arm movement in behaving octopuses. Investigating
how organisms can acutely regulate protein structure and function to alter behavior is novel and will provide
fundamental insight into mechanisms of translation, signal transduction, and evolution.
