Each month, the OVPR highlights the past month’s sponsored research funding awarded to Tufts’ investigators, including both a list of funded awards and one or more featured project abstracts.
You can download the list of September’s awardees by clicking the button below. In September, Tufts researchers received 57 awards for extramural funding from federal, foundation, and corporate sponsors.
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This month we are highlighting two awards. The first, awarded to Dr. Noorjahan Pajwani, Professor of Opthalmology, is her NIH funded project ‘The role of galectin-8 in the regulation of corneal infection and inflammation.’ The second, awarded to Dr. Matthias Scheutz, Professor of Computer Science, is his Air Force Office of Scientific Research funded project ‘Enabling Trusted Human-Like Artificial Teammates.’ Information about each project is available below.
PI: Noorjahan Pajwani
Title: The role of galectin-8 in the regulation of corneal infection and inflammation
Abstract: The bacterium Pseudomonas aeruginosa (PA) is a leading cause of microbial infection of the cornea. One of the serious consequences of PA corneal infection is blindness resulting from persistent corneal inflammation. Approximately 30,000 cases of microbial keratitis occur annually in the United States. The innate immune system is the first line of defense against pathogens and is initiated by pattern recognition receptors which respond to invading microbes. It is known that IL-1β plays an important role in the induction of immune response in PA keratitis. In the classical immune response to bacterial infection, generation of mature IL-1β is a two-step process. The first step is the induction of pro-IL-1β expression, which is generally achieved by TLR-mediated activation of NF-B pathway that results in the induction of pro-IL-1β. A second signal then triggers the assembly of inflammasomes leading to the cleavage of caspase-1. Active (cleaved) caspase-1 cleaves pro-IL-1β to generate active IL-1β, which is secreted from the cell to mediate downstream inflammatory effects that clear the infection. Recently, we have made an exciting observation that galectin-8 knockout (Gal-8 KO) mice are resistant to PA infection. Additional pilot studies revealed that Gal-8 has the potential to regulate the activation of both TLR and inflammasome pathways. The goal of this project is to characterize the role of Gal-8 in the regulation of PA-induced immunopathology, and to develop effective strategies for prevention and regression of uncontrolled inflammatory response that results in extensive damage to the cornea and visual impairment. In Aim 1, in an effort to understand the mechanisms that render Gal-8 KO mice resistant to PA keratitis, we will test the hypothesis that Gal-8 has the capacity to dampen inflammasome-mediated generation of mature IL-1β to influence innate immune response. Specifically, in this Aim, using Gal-8 KO mice and Gal-8 deficient macrophages and neutrophils, we will characterize the role of Gal-8 in the regulation of the inflammasome pathway in PA keratitis. In Aim 2, we will determine whether Gal-8 influences the outcome of PA keratitis by modulating neutrophil elastase and/or TLR pathway. To better characterize the role of Gal-8 in the pathogenesis of PA keratitis, in Aim 3A, we propose to perform transcriptome and cytokine/chemokine proteome analyses of PA-infected corneas of WT and Gal-8 KO mice, and WT and Gal-8 KO macrophages and neutrophils. In Aim 3B, studies will be performed to determine whether Gal-8 can be targeted to control overactive immune response and corneal inflammation in the mouse model of PA keratitis. We expect that the proposed study will provide ground-breaking data, not only for understanding the molecular mechanism of PA keratitis, but also for the development of novel, galectin-based therapy that can treat blinding immunopathology resulting both from bacterial keratitis, as well as from other ocular disorders, such as corneal graft rejection and dry eye disease.
PI: Matthias Scheutz
Funder: Air Force Office of Scientific Research
Title: Enabling Trusted Human-Like Artificial Teammates
Abstract: Please see the following article prepared by the School of Engineering for more information about this project: https://engineering.tufts.edu/news/2018/10/artificial-teammates