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Understanding Lectins' network language with chemical tools: new insights for immunological purposes.

Project description

Insight into dendritic cell function

Dendritic cells (DCs) activate the innate part of the immune system by processing and presenting antigens to T cells. Recognition of carbohydrates takes place through transmembrane C-type lectin receptors (CLRs) on DC surface. To understand how the chemical nature of these antigens influences internalisation, trafficking and presentation, scientists of the EU-funded LectiNet project propose to study the engagement of antigens on CLRs. For this purpose, they will develop heterogenous multivalent polymers as vectors to selectively deliver antigens to DCs and study the downstream events. Results will provide fundamental knowledge on the mechanism of action of the most potent antigen-presenting cells of the immune system.

Objective

Dendritic cells (DCs) are the most potent antigen-presenting cells due to their ability to prime T-cell immune responses. The numerous endocytic transmembrane receptors located on their surface can recognise and process endogenous and exogenous antigens. Despite DCs being efficient sentinels, pathogens, unfortunately, in some cases can evade their guard, and cause viral, bacterial infections, and cancer. The DCs mechanisms behind the lack or the presence of an immune response are not fully understood.
Chemistry offers powerful tools to prepare synthetic antigens, mimicking the natural one. Synthetic antigens can, not only be exploited to disclose the relationship between the antigen chemical structure and its processing by the immune cells but also used to train the immune system to fight pathogens. The overall aim of LectiNet is to reveal how cooperative engagement of human C-type lectin receptors (CLRs) on DCs surface influences antigen internalisation, trafficking, and presentation. This will be achieved by targeting CLRs with heterogenous multivalent polymers and analysing DC signaling and antigen routing. LectiNet hence will disclose multitarget polymers as vectors to selectively deliver antigens through DCs following a pre-designed pathway to fight viral infection and cancer.
In this global fellowship, I will benefit from the joint supervision of Professor Laura L. Kiessling from MIT and of Professor Paul V. Murphy from NUIG. LectiNet will provide me an excellent training to complement my current knowledge in synthetic chemistry, with immunology cell biology and polymer chemistry, placing me in a unique interdisciplinary area in the European research scenario. LectiNet will explore novel delivery strategies of vaccines for infectious disease and cancer and provide novel insights into the role of CLRs co-engagement.

Coordinator

UNIVERSITY OF GALWAY
Net EU contribution
€ 275 561,28
Address
UNIVERSITY ROAD
H91 Galway
Ireland

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Region
Ireland Northern and Western West
Activity type
Higher or Secondary Education Establishments
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Total cost
€ 275 561,28

Partners (1)