Event Title

Cytoplasmic Aggregates Of Human Tdp-25 Protein In C. Elegans Challenge Proteostasis

Location

Lobby in front of Auditorium

Start Date

19-4-2019 11:00 AM

Department

Biology

Description

Proteostasis, the process by which a cell maintains protein production, folding, and degradation is critical for survival; however, the fidelity of this process declines with age. Disturbance of proteostasis contributes to many age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), leading to the accumulation of misfolded proteins. Patients with this disease accumulate an aggregated form of the ALS associated protein TDP-43 in neurons, suggesting a disruption in proteostasis. Here, we are using the nematode C. elegans to examine how a toxic fragment of TDP-43, called TDP-25, challenges proteostasis. C. elegans is our model of choice because of its short life cycle, its transparent nature, and conservation of genes with human homologues. We have generated multiple transgenic lines expressing fluorescently tagged TDP-25 in the body wall muscles of the animal. Using gel electrophoresis followed by Western Blot Analysis, I will evaluate the steady state level of TDP-25 in each of the three transgenic lines during development and aging. Furthermore, the aggregation state of TDP-25 will be monitored with an expectation that the aggregation level increases with age. The strain with the highest steady state level will be identified and then aggregation will be examined. We anticipate a high level of TDP-25 will lead to an increase in aggregation in aging animals by challenging proteostasis.

Comments

Cindy Voisine is the faculty sponsor of this poster.

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Apr 19th, 11:00 AM

Cytoplasmic Aggregates Of Human Tdp-25 Protein In C. Elegans Challenge Proteostasis

Lobby in front of Auditorium

Proteostasis, the process by which a cell maintains protein production, folding, and degradation is critical for survival; however, the fidelity of this process declines with age. Disturbance of proteostasis contributes to many age-related neurodegenerative diseases, such as Amyotrophic Lateral Sclerosis (ALS), leading to the accumulation of misfolded proteins. Patients with this disease accumulate an aggregated form of the ALS associated protein TDP-43 in neurons, suggesting a disruption in proteostasis. Here, we are using the nematode C. elegans to examine how a toxic fragment of TDP-43, called TDP-25, challenges proteostasis. C. elegans is our model of choice because of its short life cycle, its transparent nature, and conservation of genes with human homologues. We have generated multiple transgenic lines expressing fluorescently tagged TDP-25 in the body wall muscles of the animal. Using gel electrophoresis followed by Western Blot Analysis, I will evaluate the steady state level of TDP-25 in each of the three transgenic lines during development and aging. Furthermore, the aggregation state of TDP-25 will be monitored with an expectation that the aggregation level increases with age. The strain with the highest steady state level will be identified and then aggregation will be examined. We anticipate a high level of TDP-25 will lead to an increase in aggregation in aging animals by challenging proteostasis.