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IMPACT SIGNED
Immune Mechanisms of Necrotic DNA Phagocytosis by Neutrophils: A Role for Integrins
Total Cost €
0EC-Contrib. €
0Partnership
0Views
0IMPACT project word cloud
Explore the words cloud of the IMPACT project. It provides you a very rough idea of what is the project "IMPACT" about.
frequently
debris
molecule
vivo
labelling
inflammatory
phagocytes
integrity
severe
tlr9
coated
showing
injury
levels
receptor
liver
day
intravital
body
internalize
good
hypothesis
favor
subset
combine
cr3
microscopy
coverslip
trauma
remove
models
inherently
recruited
connected
sensing
organisms
removal
death
loses
improper
left
reports
scarce
necrotic
plasma
mediated
billions
degrade
promotes
confocal
pro
atherosclerosis
understand
multicellular
phagocytic
damage
cell
abundant
membrane
peptides
mechanical
integrins
adhesion
vitro
acute
cells
unknown
sites
phagocytose
act
therapies
necrosis
chemical
cellular
neutrophils
cd18
amount
complement
thermal
candidates
dna
beta2
thought
deposit
diseases
surprise
erythematosus
modulation
existence
express
phagocytosis
release
eliminate
activation
lupus
bind
cd11b
Project "IMPACT" data sheet
The following table provides information about the project.
| Coordinator |
KATHOLIEKE UNIVERSITEIT LEUVEN
Organization address contact info |
| Coordinator Country | Belgium [BE] |
| Total cost | 178˙320 € |
| EC max contribution | 178˙320 € (100%) |
| Programme |
1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility) |
| Code Call | H2020-MSCA-IF-2018 |
| Funding Scheme | MSCA-IF-EF-ST |
| Starting year | 2020 |
| Duration (year-month-day) | from 2020-01-01 to 2024-01-01 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | KATHOLIEKE UNIVERSITEIT LEUVEN | BE (LEUVEN) | coordinator | 178˙320.00 |
Map
Project objective
Cell death is inherently connected to the existence of multicellular organisms. Our body loses billions of cells a day due to thermal, mechanical or chemical damage in a cell death process with loss of plasma membrane integrity and pro-inflammatory properties known as necrosis. Organisms face necrosis frequently, thus, there must be specific pathways to remove the large amount of cellular debris left behind. In this way, it is no surprise that improper removal of cellular debris, such as DNA, is associated to inflammatory diseases as lupus erythematosus, acute liver injury, atherosclerosis and severe trauma. Removal of necrotic debris is thought to be mediated by phagocytes, although reports showing it are scarce. Neutrophils, a subset of phagocytes, are good candidates for debris removal since they are abundant and quickly recruited to necrotic sites. The means used by neutrophils to identify, internalize and degrade necrotic DNA are currently unknown, thus, the main objective of my project is to understand how neutrophils phagocytose and eliminate necrotic DNA debris. Neutrophils express the DNA-sensing receptor TLR9, which is not a phagocytic receptor. However, they also express very high levels of beta2 integrins such as CD11b/CD18, which act as adhesion molecule and as complement receptor (CR3). The release of necrotic DNA promotes complement activation in vivo through several pathways, therefore, my hypothesis is that neutrophils use beta2 integrins to bind and phagocytose complement-coated necrotic DNA. To assess the role of beta2 integrins, TLR9 and complement in phagocytosis of necrotic DNA by neutrophils, I will combine a novel in vitro method (DNA deposit in coverslip) with an in vivo approach (confocal intravital microscopy). I will also develop novel peptides for DNA labelling and modulation of phagocytosis, which I will use in both models. The findings of this project will directly favor the development of novel therapies for inflammatory diseases.
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No valid XML
lastchecktime (2024-04-19 22:34:56) correctly updated