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CL_Exocytosis SIGNED

“Molecular dissection of cytotoxic lymphocyte exocytosis

Total Cost €

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EC-Contrib. €

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Partnership

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 CL_Exocytosis project word cloud

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Project "CL_Exocytosis" data sheet

The following table provides information about the project.

Coordinator
KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
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 Coordinator Country Sweden [SE]
 Total cost 173˙857 €
 EC max contribution 173˙857 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 173˙857.00

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 Project objective

My PhD experience in the field of immunology focused on deciphering vesicular pathways underlying T cell activation profoundly motivated my move to Dr. Bryceson’s lab, which offers a unique opportunity to explore cytotoxic lymphocyte (CL) exocytosis in the context of human disease. Cytotoxic lymphocyte exocytosis is critical for life, with mutations in genes required for cytotoxicity causative of severe, early-onset hyperinflammatory syndromes. Genetic studies have identified several cytosolic proteins required for CL exocytosis. However, understanding of how these proteins cooperate for exocytosis, their interaction partners and how their activities are regulated is still limited. I propose strategies to gain insight to the molecular regulation of human CL exocytosis. First, prompted by genetic studies, I aim to study the contribution of two distinct Munc13-4 isoforms to lymphocyte cytotoxicity by dissecting their role in cytotoxic granule (CG) exocytosis using advanced live-cell imaging as well as identifying their interaction partners using quantitative mass spectrometry (MS). Second, recycling endosome (RE) have recently been implicated in CG exocytosis, delivering syntaxin-11, an effector molecule required for CG fusion, to the plasma membrane. I plan to use a high-throughput MS approach to identify RE constituents and cargo in order to define new components that may be critical for CG exocytosis. Results will provide novel mechanistic insights to CL exocytosis, which will also be relevant for other exocytic systems. Providing detailed molecular understanding of lymphocyte cytotoxicity in both healthy and pathological conditions, insights promise to guide improved diagnosis and therapy of immune disorders associated with defects in lymphocyte cytotoxicity. Yearning to build a successful academic career, the excellence of the host laboratory will allow me to successfully purse this project and expand technical expertise and my scientific horizon.

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The information about "CL_EXOCYTOSIS" are provided by the European Opendata Portal: CORDIS opendata.

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