With the remarkable capacity to form complete individuals from tiny body fragments, planarian flatworms represent a valuable model organism for research on cellular and molecular mechanisms of regeneration. One important objective in this field is to determine how changes in gene expression are triggered in response to injury, in order to initiate the regenerative response. The overall goal of this project is to addresses the hypothesis that the nonsense-mediated mRNA decay pathway (NMD), a cellular surveillance mechanism with emerging roles in stem cells and their division progeny, orchestrates posttranscriptional control of gene expression during regeneration.
Specific aims i nclude 1) analyzing the effects of RNAi knockdown of conserved NMD factors on cellular events that occur following amputation, including stem cell proliferation and migration to the wound site; 2) identifying planarian NMD target mRNAs through an RNA-Seq approach, and determining their specific functions using RNAi and in situ hybridization; and 3) determining how specific transcripts are designated for NMD. Completion of the proposed objectives will improve our understanding of how gene expression is regulated during regeneration, and has the potential to reveal new avenues for clinical intervention in the treatment of human injury or degenerative disease. Additionally, the project will afford undergraduate students at Keene State College an opportunity to engage in discovery- based research relevant to the rapidly growing field of regenerative medicine.

Public Health Relevance

The field of regenerative medicine seeks the development of new treatments for tissue loss or damage resulting from physical injury or disease. By studying naturally occurring regenerative processes in simple model organisms, conserved repair mechanisms representing candidate clinical targets can be identified and characterized. The goal of this proposal is determine the role of one such mechanism, the nonsense-mediated mRNA decay pathway, in the dramatic regenerative abilities of planarian flatworms.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15GM126456-01
Application #
9442417
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Salazar, Desiree Lynn
Project Start
2018-02-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2020-01-31
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Keene State College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
110379158
City
Keene
State
NH
Country
United States
Zip Code