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Engineering Neuroresilience: Investigating Tardigrade Neuroprotection to Identify Translatable Strategies

Award Number: K99AG097967
ORGANIZATION: NATIONAL INSTITUTE ON AGING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Engineering Neuroresilience: Investigating Tardigrade Neuroprotection to Identify Translatable Strategies - PROJECT SUMMARY: The stability and resilience of the nervous system and the long-term survival of neurons are critically important to human health. Many neurological and neurodegenerative disorders result in irreversible and debilitating loss of neuronal function and vital synaptic connectivity. Currently, over 87 million people suffer from lasting impairments resulting from stroke, and 57.4 million people worldwide suffer from neurodegenerative diseases, which will increase precipitously as our population continues to age. The proposed research will explore how nervous systems are maintained when faced with exposure to extreme environmental stressors, with the aim of identifying new approaches to prevent neuronal damage during the normal aging process and in the diseased state. To evaluate neuronal resilience in extreme conditions, we will use the hyper-resilient invertebrate species, the tardigrade Hypsibius exemplaris, which has the unique ability to survive near-complete desiccation, osmotic stressors, near-complete anoxia and, as I recently discovered, 1 million times the force of earth’s gravity (hypergravity) for over 30 minutes. These animals survive osmobiosis and anoxia by entering a cryptobiotic (inanimate) state of metabolic suspension, accompanied by gross morphological and physiological changes. Following reanimation from cryptobiosis, the animals return to normal movement in minutes, following a brief period of visibly uncoordinated movement. This suggests that the tardigrade nervous system remains grossly unperturbed or readily recovers from these stresses. A critical question is how a nervous system remains stable to such extraordinary stresses. The proposed research will test the hypothesis that the tardigrade nervous system undergoes rapid morphological, physiological, and molecular changes and is equipped with specific neuroprotective molecular tools to maintain or rapidly return to homeostasis. I will first explore anatomical changes to synapse density and neuronal ultrastructure during osmotic and anoxic shock by direct visualization of nervous system architecture using eFIB-SEM and TEM. These studies will generate the first whole-animal connectome for H. exemplaris, among the most compact nervous systems of any limbed animal and will directly compare the reference connectome with subsampled TEM reconstructions of cryptobiotic states (Aim 1). Further, I will assess behavioral and physiological impacts of cryptobiosis by functional imaging of neuronal activity and direct quantification of interlimb coordination and locomotive behaviors (Aim 2). Finally, using RNAi knockdown, I will assess the requirement of selected candidate proteins identified from existing transcriptomic datasets in promoting nervous system resilience and analyze their impact on survival and neural function (Aim 3).


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 = $123,066 )
2026	2026	UNIVERSITY OF CALIFORNIA, SANTA BARBARA	3227 CHEADLE HALL	SANTA BARBARA	CA	93106	SANTA BARBARA	USA	Aging Research	000	1	9/4/2026	NEW	$123,066
														Subtotal = $123,066

Grand Total All Awards = $123,066

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Engineering Neuroresilience: Investigating Tardigrade Neuroprotection to Identify Translatable Strategies

Award Number: K99AG097967

ORGANIZATION: NATIONAL INSTITUTE ON AGING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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