Submission Date

7-23-2026

Document Type

Paper- Restricted to Campus Access

Department

Biochemistry & Molecular Biology

Faculty Mentor

Erica Gorenberg

Comments

Presented during the 28th Annual Summer Fellows Symposium, July 24, 2026 at Ursinus College.

The file available for download is a PowerPoint slide presentation.

Project Description

Protein aggregation is a defining feature of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), often driven by liquid–liquid phase separation (LLPS). TAR DNA-binding protein 43 (TDP-43) is a key aggregation-prone protein in these diseases, with its low-complexity domain (LCD) implicated in mediating protein–protein interactions, phase separation, and aggregation. This study investigates whether the LCD of TDP-43 is sufficient to recruit other proteins into aggregates. To investigate this, recombinant constructs were generated using Gibson assembly to fuse full-length TDP-43 and its LCD to red and green fluorescent proteins, respectively (RFP and GFP). These constructs will be expressed in Saccharomyces cerevisiae to allow visualization of protein localization and aggregation in vivo. Fluorescence microscopy will be used to assess colocalization between full-length TDP-43 and LCD-containing fusion proteins. We hypothesize that the LCD region of TDP-43 is sufficient to direct other proteins to TDP-43 aggregation sites, resulting in observable colocalization of fluorescent signals. Characterizing the role of the LCD in protein recruitment will provide insight into how we can take advantage of this innate ability of the LCD region and target chaperones to protein aggregates.

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