Summary
DILEMMA will orient fundamental research to fill a gap in diabetes mellitus (DM) biology, by addressing a relevant biomedical problem in a cross-disciplinary manner, with great societal and economic impact. I will use a unique combination of advanced nanoscopy with protein biochemistry and cell biology.
Clinical studies identified stiffening in vascular, muscle and connecting tissues as particular mechanical fingerprints for DM. In diabetic patients advanced glycation end products are clinical biomarkers of DM that correlate with increased heart failure risk, but the mechanism of action bridging the mechanical alterations at molecular and tissue levels remains elusive. Current techniques used to inspect biochemical regulation of proteins fall short at describing the interplay between their dynamics under force and biological function. An in-depth multiscale characterization of the mechanical landscape in DM is a promising approach to identify new mechanical biomarkers able to advance therapeutic and diagnostic strategies. DILEMMA will study the fundamental link between tissue stiffening and protein glycation modifications in DM at multiple scales relevant for mechanobiology. I will explore the hypothesis that in diabetic patients lamin proteins are modified by glycation, which disrupts nuclear mechanical homeostasis. DILEMMA will have a strong impact in DM biology by providing new tools to understand how protein glycation and nuclear mechanics set the mechanical properties of cells and tissues in pathophysiological conditions.
I will receive training and education to acquire or strengthen my technical, scientific, and soft skills. This action will impact my career, representing a jump that will advance my future goal of becoming an independent young leader and establishing a unique research line at national level. DILEMMA could improve future clinical practice and reduce economic burden on the health system.
Clinical studies identified stiffening in vascular, muscle and connecting tissues as particular mechanical fingerprints for DM. In diabetic patients advanced glycation end products are clinical biomarkers of DM that correlate with increased heart failure risk, but the mechanism of action bridging the mechanical alterations at molecular and tissue levels remains elusive. Current techniques used to inspect biochemical regulation of proteins fall short at describing the interplay between their dynamics under force and biological function. An in-depth multiscale characterization of the mechanical landscape in DM is a promising approach to identify new mechanical biomarkers able to advance therapeutic and diagnostic strategies. DILEMMA will study the fundamental link between tissue stiffening and protein glycation modifications in DM at multiple scales relevant for mechanobiology. I will explore the hypothesis that in diabetic patients lamin proteins are modified by glycation, which disrupts nuclear mechanical homeostasis. DILEMMA will have a strong impact in DM biology by providing new tools to understand how protein glycation and nuclear mechanics set the mechanical properties of cells and tissues in pathophysiological conditions.
I will receive training and education to acquire or strengthen my technical, scientific, and soft skills. This action will impact my career, representing a jump that will advance my future goal of becoming an independent young leader and establishing a unique research line at national level. DILEMMA could improve future clinical practice and reduce economic burden on the health system.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101065552 |
| Start date: | 01-06-2022 |
| End date: | 31-05-2024 |
| Total budget - Public funding: | - 181 152,00 Euro |
Cordis data
Original description
DILEMMA will orient fundamental research to fill a gap in diabetes mellitus (DM) biology, by addressing a relevant biomedical problem in a cross-disciplinary manner, with great societal and economic impact. I will use a unique combination of advanced nanoscopy with protein biochemistry and cell biology.Clinical studies identified stiffening in vascular, muscle and connecting tissues as particular mechanical fingerprints for DM. In diabetic patients advanced glycation end products are clinical biomarkers of DM that correlate with increased heart failure risk, but the mechanism of action bridging the mechanical alterations at molecular and tissue levels remains elusive. Current techniques used to inspect biochemical regulation of proteins fall short at describing the interplay between their dynamics under force and biological function. An in-depth multiscale characterization of the mechanical landscape in DM is a promising approach to identify new mechanical biomarkers able to advance therapeutic and diagnostic strategies. DILEMMA will study the fundamental link between tissue stiffening and protein glycation modifications in DM at multiple scales relevant for mechanobiology. I will explore the hypothesis that in diabetic patients lamin proteins are modified by glycation, which disrupts nuclear mechanical homeostasis. DILEMMA will have a strong impact in DM biology by providing new tools to understand how protein glycation and nuclear mechanics set the mechanical properties of cells and tissues in pathophysiological conditions.
I will receive training and education to acquire or strengthen my technical, scientific, and soft skills. This action will impact my career, representing a jump that will advance my future goal of becoming an independent young leader and establishing a unique research line at national level. DILEMMA could improve future clinical practice and reduce economic burden on the health system.
Status
TERMINATEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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