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dc.contributor.advisorWang, Jiou
dc.creatorVelasquez, Adan A
dc.date.accessioned2020-06-21T20:37:16Z
dc.date.created2020-05
dc.date.issued2020-04-30
dc.date.submittedMay 2020
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/62682
dc.description.abstractAn increasingly aging population has contributed to the rise in of age-related illness, such as Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). A major causal factor of FTD and ALS is the C9orf72 hexanucleotide repeat (GGGGCC), found in the non-coding region of C9ORF72. The C9orf72 hexanucleotide repeat has been shown to mediate disease through processes such as, formation of RAN translation products in neuronal inclusions, impaired autophagic induction, and increased autophagic flux. The C9orf72 protein forms a stable, co-dependent complex with SMCR8, a protein also involved in the onset of FTD/ALS. C9orf72 and SMCR8 also form a complex with WDR41 (CSW complex), which can bind to the FIP200 autophagy initiation complex. The C9orf72-SMCR8 complex and CSW complex can act as GAPs, and thus are able to stimulate the GTPase activity of Rab proteins. Similar to C9orf72, SMCR8 has been associated with the impairment of autophagy induction. However, SMCR8 has been shown to contribute to a decrease in autophagic flux. Given the involvement of SMCR8 and C9orf72 in the onset of FTD/ALS, identifying more information concerning the structure of these two proteins could increase our understanding of the mechanisms through which they cause disease. Thus, assays were performed to optimize the expression and purification of these two proteins. The methodology of these assays, along with recommendation for future experiments will be discussed.
dc.format.mimetypeapplication/pdf
dc.language.isoen_US
dc.publisherJohns Hopkins University
dc.subjectSMCR8
dc.subjectC9orf72
dc.titleOptimization of the expression and purification of SMCR8 and C9orf72
dc.typeThesis
thesis.degree.disciplineBiochemistry
thesis.degree.grantorJohns Hopkins University
thesis.degree.grantorBloomberg School of Public Health
thesis.degree.levelMasters
thesis.degree.nameSc.M.
dc.date.updated2020-06-21T20:37:16Z
dc.type.materialtext
thesis.degree.departmentBiochemistry and Molecular Biology
local.embargo.lift2024-05-01
local.embargo.terms2024-05-01
dc.contributor.committeeMemberHamacher-Brady , Anne
dc.publisher.countryUSA


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