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Polyphosphate Utilization in Living Systems of Mammals and their Effects

Project description

Understanding polyphosphate role in mammals

Polyphosphates (polyP) are essential in mammalian cells for energy metabolism, blood coagulation and signalling. Revealing their functions in mammals will enhance our understanding of their role in human health. Supported by the Marie Skłodowska-Curie Actions programme, the PULSE project will explore how polyP levels influence cellular activity. It will measure metabolic activity, transcriptional changes and morphological alterations by manipulating polyP abundance in specific subcellular compartments through the expression of polyphosphate kinase and exopolyphosphatases. The project will also investigate the role of polyP in liver health and acetaminophen toxicity using a novel mouse model. Additionally, it will include human tissue samples from the UKE facility to examine polyP levels in relation to specific pathologies.

Objective

PULSE: Polyphosphate Utilization in Living Systems of Mammals and their Effects. Here, we propose to uncover how mammalian systems utilize polyphosphate (polyP) and what roles it may play in health. First, we introduce a novel approach to understand how polyP levels affect cellular activity. We propose measuring metabolic activity, transcriptional differences, and morphological conditions induced by manipulating the abundance of polyP in specific subcellular compartments. To do this, we have developed a system to express either polyphosphate kinase (PPK) or exopolyphosphatases (PPX) in specific compartments to increase or decrease the polyP levels, respectively.

We further propose to interrogate the role polyP plays in liver health and acute liver damage caused by acetaminophen (APAP) toxicity. We will use a novel mouse model with ectopic expression of PPX to decrease the level of polyP present in the liver to determine the effect of polyP abundance on liver tissue response to acute APAP injury. We will analyze the pathology of the tissue through multiple methods including serum biomarkers, histopathology, immunohistochemistry, intravital multi-photon imaging, and pulsed-infrared laser-based tissue proteomics. In addition, using human patient samples from the UKE facility, we can analyze polyP levels in human tissue based on human-specific pathologies, allowing us to expand our study to include patient-relevant data.

At the conclusion of this project, we will substantially expand the baseline understanding of how mammalian systems utilize polyP. With the work from our mouse model, we will have a clearer understanding of what role polyP plays in the health of mammals. The additional data we will generate from human patient samples will allow us direct understanding into the role of polyP in human health as well.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF
Net EU contribution
€ 202 125,12
Address
Martinistrasse 52
20251 Hamburg
Germany
Region
Hamburg Hamburg Hamburg
Activity type
Higher or Secondary Education Establishments
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Total cost
No data