Functional, molecular, and biophysical aspects of temperature activation of an insect thermosensory ION channel

Active Project Grant Awarded Last action

Award ID
F31NS145533
Recipient
Awarding agency
Obligated
$44,703

Award facts

Assistance listing
93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders
Completion date 0% complete
Place of performance
Evanston, IL 60208, USA

Award details come from USAspending.gov.

Description

Abstract
Temperature sensing is an important constituent of the human somatosensory and pain systems, and a number of conditions originate from or include dysfunctional or aberrant ability to sense thermal stimuli. However, many of the principles and mechanisms of thermosensation remain unknown. At the core of a thermosensory neuron's ability to detect changes in external temperature are specific thermosensory ION channels that are directly activated (GATED) by temperature in specific ranges. The best known thermosensory channels belong to the transient receptor potential (TRP) family and are the main mediators of hot and cold sensation in humans. Temperature sensing is an ancient and fundamental sensory modality, and yet thermosensory neurons do not appear to universally use TRP channels as thermosensors. For example, in insects, key molecular thermosensors seem to have independently evolved from families of ION channels that are otherwise populated by olfactory (IRS) and gustatory (GR) receptors. Here, I propose to study the mechanism of temperature gating of GR28B.D, a recently described ION channel that functions as the main transducer of innocuous heat in drosophila and that is molecularly and structurally unrelated to the TRP channels. By comparing temperature- sensitive and temperature-insensitive variants of GR28B in vitro (and by producing chimerae between the two), my work will reveal the molecular determinants of heat gating of GR28B.D. Moreover, I will produce chimeric constructs starting from GR28B.D sequences that belong to fly species adapted to different thermal environments to understand how activation mechanism may have changed across evolution. Finally, I will explore the possibility that GR28B.D may be used in the context of heat seeking by blood-sucking tsetse flies. My proposal is relevant from a fundamental perspective because IT will reveal new mechanisms of heat sensing by an ION channel that is structurally unrelated to trps, while also potentially laying the groundwork for a better understanding of heat seeking in insect vectors of disease.

Quick answers

Who received award F31NS145533?

F31NS145533 was awarded to Northwestern University by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on December 1, 2026.

How much is award F31NS145533 worth?

$44,703 has been obligated on F31NS145533.

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