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

Award Number: F31NS145533
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2026
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Functional, molecular, and biophysical aspects of temperature activation of an insect thermosensory ion channel - PROJECT SUMMARY/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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $44,703 )
2026	2026	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/11/2026	NEW	$44,703
														Subtotal = $44,703

Grand Total All Awards = $44,703

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

Award Number: F31NS145533

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2026

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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