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Unraveling the role of O-glycosylation in pancreatic ductal adenocarcinoma.

Project description

Glycosylation in pancreatic cancer

Glycosylation is a common post-transcriptional modification of both proteins and lipids. It plays a central role in the regulation of cell function and immune responses. Pancreatic ductal adenocarcinoma (PDAC) is characterised by distinct glycosylation patterns. With the support of the Marie Skłodowska-Curie Actions programme, the GlycoPDAC project will investigate how glycosylation drives PDAC progression. Researchers will focus on specific glycosylating enzymes and identify which proteins they modify as well as their impact on tumour behaviour and immune evasion. By uncovering subtype-specific glycosylation mechanisms, the project aims to reveal new biomarkers and therapeutic targets to improve early detection and treatment strategies for PDAC.

Objective

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive cancer type, with a 5-year survival rate of just 10%. This is primarily due to late-stage diagnosis and resistance to current treatments. Therefore, understanding the molecular mechanisms driving PDAC progression is critical for developing more effective diagnostic and therapeutic approaches.
Glycosylation, one of the most prevalent post-translational modification, is fundamentally altered in PDAC. The two clinically significant subtypes present in PDAC, called Classical and Basal, have distinct glycosylation profiles that affect tumor cell biology and its interactions with the microenvironment and immune system. Despite its importance, the particular mechanisms involved are poorly understood.
This project aims to elucidate how glycosylation drives PDAC, by characterizing the glycoproteins involved in different subtypes. We are particularly focus in the glycosylation enzymes GalNAc-T1 and GalNAc-T3, which have fundamental yet distinct roles in Classical and Basal cancer cells. However, their substrate proteins and underlying mechanisms remain largely unknown. Using bump-and-hole engineering, combined with click chemistry and mass spectrometry, we will pinpoint the glycoprotein substrates and glycosylation sites modified by these isoenzymes, offering unparalleled insight into the roles of glycans in PDAC.
We will also characterize the biological functions of these glycoproteins through biochemical, cell biology, and immunological methods. By revealing how these glycoproteins influence cancer cell biology and immune recognition, this project could uncover novel mechanisms involved in PDAC progression, which can lead to the identification of new biomarkers or therapeutic targets, potentially improving patient outcomes.

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

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
1 MIDLAND ROAD
NW1 1AT London
United Kingdom

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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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