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Mechanisms Driving Regenerative Neurogenesis in Planarians

Award Number: R01NS128096
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2027

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Mechanisms Driving Regenerative Neurogenesis in Planarians - Project Summary Humans regenerate tissue of the brain and spinal cord poorly. Failure to regenerate missing or damaged cells impedes survival and recovery after neurodegenerative disease, stroke, traumatic or ischemic injury, or developmental error. Unlike humans, other animals can effectively repair dramatic injuries or damage within the central nervous system. Free-living freshwater flatworms called planarians possess extraordinary regenerative abilities, including flawless regeneration and replacement of all brain and nerve cord tissues. After tissue loss or damage, planarians remodel existing tissue and use adult pluripotent stem cells to replace diverse cell types, including dozens of types of neurons. Planarians create neurons in appropriate ratios and then repattern and reconnect neurons to targets to restore function. The long-term goal is to discover the molecular and cellular basis of robust neural regeneration using planarians. Toward that objective, the first specific aim is to identify and characterize factors important for regenerative neurogenesis from pluripotent stem cells, focusing first on regeneration of dopaminergic neurons. Four transcription factor-encoding genes important for regeneration and maintenance of dopaminergic neuron subtypes have already been discovered. The following specific aims will provide critical information about how environmental cues promote brain regeneration by pluripotent stem cells in vivo. The second specific aim is to test the hypothesis that neurogenesis is upregulated in planarians after injury, through wound-induced signaling mechanisms. The third specific aim is to test the hypothesis that planarian neurogenesis is driven by polarity cues so that new neurons of the correct types are created in the proper locations. The proposed work in this application is conceptually innovative because of the use of a highly regenerative model organism to explore regenerative neurogenesis and because of the development of new molecular and behavioral assays (e.g. DAP-Seq, live prey assays). The proposed research is significant because it will provide a foundational understanding of successful neural regeneration in response to injury, with a long-term goal of identifying pathways or molecular mechanisms that could be leveraged to improve human regenerative therapies.


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: 2025 ( Subtotal = $377,500 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/6/2025	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2024 ( Subtotal = $366,175 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/16/2024	NON-COMPETING CONTINUATION	$366,175
														Subtotal = $366,175

Issue Date FY: 2023 ( Subtotal = $377,500 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/16/2023	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2022 ( Subtotal = $333,900 )
2022	2022	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/9/2022	NEW	$333,900
														Subtotal = $333,900

Grand Total All Awards = $1,455,075

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Mechanisms Driving Regenerative Neurogenesis in Planarians

Award Number: R01NS128096

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/15/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2027

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