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Development of a novel screening platform for identifying genetic pathways regulating axon regeneration
Lo, Tsz
Lo, Tsz
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Thesis/Dissertation
Date
2022
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Bioengineering
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http://dx.doi.org/10.34944/dspace/7990
Abstract
In the event of nervous system trauma, there are currently no treatments for functional loss due to thefailure of the mature mammalian central nervous system (CNS) to regenerate. Reduced intrinsic growth
ability is believed to be a factor in attributing to the persistent functional deficits in neurological disorders
such as spinal cord injury. Our candidate-based genetic screen allows us to examine and reveal several
novel targets and pathways that have never been implicated in axon regeneration. However, we still lack a
complete understanding of the repertoire of genetic factors that can promote or inhibit axonal regrowth
after neural damage.
Given that neurons have polarized morphology with distinct cellular compartments, microfluidic
platforms had gained considerable impact in neuroscience research. Furthermore, disrupting gene
expression is a common approach to understanding the loss-of-function disease mutations. Due to its
many advantages, CRISPR technology is an attractive tool to irreversibly remove the gene of interest by
targeting its DNA.
The overall goal is to identify negative regulators in axon regeneration. Here, we performed candidatebased studies to assess novel candidates in neural regulation (Piezo, Atr, Nup188) and developed several
novel axon transection microfluidics platforms that cater to various needs of current research. Results of
this integrative approach can either be individually exploited to further neuroscience research or be taken
together to result in a list of negative regulators that are potentially suitable as axon disconnection therapy
targets.
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