# Synaptopodin and its role in Shigella flexneri intercellular spread > **NIH NIH F32** · UNIVERSITY OF COLORADO DENVER · 2024 · $76,328 ## Abstract Project Summary/Abstract Shigella are bacterial pathogens that are a major source of moderate-to-severe diarrhea, and globally, a leading cause of long-term disability and disease in children. Illness necessitates Shigella invade epithelial cells lining the colon and then spread between the cells of the epithelial monolayer. This type of spread enables bacteria to avoid immune detection while acquiring nutrients and increasing the size of their replicative niche, thus intercellular spread is essential for severe disease. To spread, Shigella repurposes the actin cytoskeleton to acquire actin-based motility within cells. Shigella that move to the plasma membrane deform it into structures known as protrusions. These protrusions are essential for spread, because they enable bacteria to push into adjacent, uninfected cells. While these macroscopic steps are known, the molecular mechanisms that drive them are much less understood. Here, I propose to study the molecular mechanisms for how synaptopodin (Synpo) promotes Shigella flexneri intercellular spread. Our data demonstrate that Synpo is required for disease caused by S. flexneri, as it is essential for the bacteria to spread between cells. We show that Synpo enables the formation of longer actin fibers within the actin tail and enhances the efficiency of protrusion formation. It is unclear how Synpo promotes these processes, my preliminary data show S. flexneri infection alters the phosphorylation state of Synpo within defined or predicted protein interaction domains. I hypothesize that the phosphorylation state of Synpo is altered during infection such that Synpo forms a complex with distinct proteins during infection, enabling the recruitment and function of these proteins at sites of bacterial protrusion formation and sites where bacteria polymerize actin. To test aspects of this hypothesis, I propose the following aims: Aim 1. To define whether phosphorylation of Synpo is necessary for S. flexneri intercellular spread. Aim 2. To define whether Synpo promotes localization of host proteins to S. flexneri during infection. The completion of these aims is likely to define new mechanisms about how Synpo functions in cells and about how bacteria spread intercellularly. These approaches will further define the role of post-translational modifications of Synpo, identify proteins that interact with Synpo, and determine how Synpo is localized to particular positions within the cell. Further, many pathogens that cause diarrhea require mechanisms similar to Shigella, suggesting that my studies are likely to yield general insights into how pathogens cause diarrheal disease. ## Key facts - **NIH application ID:** 10997892 - **Project number:** 1F32AI186544-01 - **Recipient organization:** UNIVERSITY OF COLORADO DENVER - **Principal Investigator:** Desmond J Hamilton - **Activity code:** F32 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $76,328 - **Award type:** 1 - **Project period:** 2024-08-01 → 2027-07-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10997892 ## Citation > US National Institutes of Health, RePORTER application 10997892, Synaptopodin and its role in Shigella flexneri intercellular spread (1F32AI186544-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10997892. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*