| Project Information |
| Project Title: |
Regulation of LRIG1 and its functional role following brain injury. |
| Period: |
from: 2022-05-01
to: 2023-04-30
|
| Principal Investigator(s): |
Ouzikov, Stephanie
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| Co-Investigators: |
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| Supervisors: |
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| Previous Investigators/Supervisors: |
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| Institution: |
University of Toronto
|
| Department: |
Laboratory Medicine & Pathobiology |
| Agency: |
Canadian Institutes of Health Research |
| Program: |
Master's Award: Canada Graduate Scholarships |
| Keywords: |
BRAIN INJURY, CELL SIGNALLING INHIBITION, CELLULAR DIFFERENTIATION, CENTRAL NERVOUS SYSTEM, GENE EXPRESSION, GENE TARGETING, LEUCINE-RICH REPEATS AND IMMUNOGLOBULIN-LIKE DOMAINS 1, NEURAL STEM CELLS, NEUROGENESIS, STROKE |
| Abstract: |
Neural stem cells (NSCs) are largely quiescent in nature and divide infrequently for brain maintenance and during times of brain injury. However, even after stroke injury, these newborn neurons migrate to the lesion site, of which most NSC die. LRIG1 is a known regulator of neural stem cell quiescence in the brain and its downregulation was seen to cause an increase in neural stem cell proliferation during embryonic development. In my proposed study, my main objectives will be to further identify factors that regulate LRIG1 expression in the brain, in addition to further understanding the role that LRIG1 plays following stroke injury. This will enable us to reveal how gene expression and proliferative phenotypes are controlled in quiescent cell types. I will be using CRISPR/cas9 to knockout transcription factors with known roles in neural stem cell regulation, such as krüppel-like factor 15 (KLF15), c-Myc and others, in radial precursor cultures and look at LRIG1 expression. I will also extend these studies in vivo and use in-utero electroporation in order to knockout these transcription factors and assess LRIG1 expression. Next, I will be assessing the proliferative capacity of NSCs after inducing stroke in LRIG1 (fl/fl) mice crossed to a Nestin-CreERT2 line and use tamoxifen to induce KO of LRIG1. This study will further unlock the mechanisms by which LRIG1 expression is controlled in quiescent stem cell and reveal the functional role LRIG1 plays in the proliferation of NSCs in response to stroke injury.
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| Funding Information |
| Fiscal
Year |
Amount |
| 2022-23 |
$17,500
|
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