Griffith, Amber
(2019)
Characterizing The Cellular Response To Nitrogen-doped Carbon Nanocups For Potential Application In Understanding The Abscission Delay Pathway In Mammalian Cells.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Cytokinesis is the separation of two daughter cells after successful chromosome segregation. Occasionally cells face challenges during the end of cell division. I specifically investigate how cells deal with the challenge of chromatin trapped in the cleavage plane. It is understood that cells have developed a mechanism where they delay cytokinesis until the chromatin is cleared. This mechanism is conserved in yeast, mammalian cells and drosophila[1-4]. In mammalian cells, Aurora B is thought to be a key protein in delaying cytokinesis[4, 5]. What is yet to be understood is how trapped chromatin leads to the reactivation of Aurora B at the end of cytokinesis. I have explored the nature of this pathway, using fluorescence microscopy and live cell imaging. My data suggest that post-translational modifications on Aurora B changes when lagging chromatin is trapped in the cleavage plane. To understand the mechanism in more detail, I propose using carbon nanoparticles, specifically carbon nanotubes, to mimic lagging chromatin and help further characterize the pathway allowing cells to modulate cytokinesis in response to chromatin in the cleavage furrow.
In collaboration with Dr. Star in the chemistry department by using their synthesized material, I investigate how cells react to the exposure of nitrogen-doped carbon nanocups (NCNCs). Originally, NCNCs were developed to aid in delivering drug to tumors, and have been studies in mouse systems and in neutrophils[6, 7]. In my study, I have demonstrated that NCNCs are capable of entering cells, they have minimal cytotoxic effects, and protein-conjugated NCNCs can successfully enter cells. This primes NCNCs as a potential tool to be used as a signaling platform to recapitulate the abscission delay pathway in cells undergoing normal cytokinesis.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
25 September 2019 |
| Date Type: |
Publication |
| Defense Date: |
23 May 2019 |
| Approval Date: |
25 September 2019 |
| Submission Date: |
7 August 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
94 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Biological Sciences |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Biology
Cell Biology
Nanotubes
Nanotechnology |
| Date Deposited: |
25 Sep 2019 15:33 |
| Last Modified: |
25 Sep 2019 15:33 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/37320 |
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