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Investigating the Role of Mechanosensation in Axon Regeneration and Developing a Novel Screening Platform for Regulators of Regeneration / Leann Miles.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Miles, Leann, author.
- Language:
- English
- Subjects (All):
- Neurosciences.
- Biophysics.
- Biochemistry.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Local Subjects:
- Neurosciences.
- Biophysics.
- Biochemistry.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Physical Description:
- 1 online resource (179 pages)
- Contained In:
- Dissertations Abstracts International 84-08B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.
- Ann Arbor : ProQuest Dissertations & Theses, 2022
- Language Note:
- English
- Summary:
- A major focus in the field of neuroregeneration has shifted towards identifying intrinsic molecular machineries that trigger or suppress regenerative responses so that these factors can be manipulated as potential therapeutic targets. While injury paradigms in different model organisms have been established and serve as useful screening platforms, most have only been candidate-based screens that leave the majority of the genome unexplored. Therefore, new strategies are needed to identify and elucidate factors that regulate regeneration. In doing so, we can increase the rate and/or extent of axon regrowth to improve functional recoveries in the adult mammalian CNS and PNS. To address this, my thesis work is comprised of two approaches 1) to validate and characterize hits from our lab's candidate-based screens to deepen our understanding of regulators of regeneration 2) establish a platform to conduct large-scale genetic screens for regeneration mediators. Through a candidate-based screen, we know that the RNA repair and splicing pathway regulates regeneration through Rtca, a 3'-terminal phosphate cyclase involved in the unconventional splicing of Xbp1, a stress sensor. Our mechanistic studies show that Rtca regulates the expression of other proteins, namely Piezo (a mechanosensitive cation channel) and the small GTPase, Rab10, in Drosophila.Characterizing these factors has led us identify the Piezo-Atr axis as a mediator of how mechanical force regulate regeneration. Our findings also implicate the potential role of vesicular transport in axon repair and our novel discovery that Golgi outposts might also regulate axon growth reveals a phenotype not yet reported. By establishing our microfluidics system, we will be able to perform CRISPR-based (clustered regularly interspaced short palindromic repeat sequences) unbiased screen in our neural injury paradigm and contribute to our knowledge of agents involved in neuron repair.
- Notes:
- Source: Dissertations Abstracts International, Volume: 84-08, Section: B.
- Advisors: Song, Yuanquan; Committee members: Ostap, Michael; Janmey, Paul; Song, Hongjun; Huang, Xi.
- Department: Biochemistry and Molecular Biophysics.
- Ph.D. University of Pennsylvania 2022.
- Local Notes:
- School code: 0175
- ISBN:
- 9798374413014
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
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