Cel Tissue resident macrophages are essentially present in every organ of the body and perform critical functions in immunity,tissue homeostasis and regeneration. Recent evidence shows that resident macrophages can originate from embryonicprogenitors and be maintained in tissues long term by local proliferation independently of monocytes. This self-renewalability, however, appears to decline with age, with potentially major consequences for the response to infection, theresolution of inflammation and the ability for tissue regeneration. Understanding the decline of self-renewal in the agingmacrophage may thus hold key elements for maintaining healthy tissue integrity. Drawing from analogies to stem cell self-renewal we want to decipher the molecular and cellular parameters of macrophage self-renewal and its decline with age.We want to understand the age-associated changes in gene expression and epigenetic identity of tissue macrophagepopulations with the ultimate goal to reverse age dependent decline in self-renewal and function. Results from mylaboratory have identified transcription factors that control the access to a network of self-renewal genes that are also used in stem cells. Using several complementary genetic mouse models tapping into this network we want to investigate whether its activation in resident macrophage population in vivo can rejuvenate their self-renewal capacity and revert aging related changes. These approaches will be complemented by unbiased genome wide screens in vivo using latest generation CRISPR/Cas9 genome editing technology to identify new signaling pathways guiding macrophage self-renewal and aging. Using innovate combinations of genetics and adoptive transfer protocols we will test whether this knowledge can be employed to reverse macrophage dependent loss of immune competence and failed tissue regeneration with age. Our results will lead to new general insight and potential novel cellular therapies for degenerative diseases. Dziedzina nauki medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsgenomesmedical and health sciencesbasic medicinephysiologyhomeostasis Słowa kluczowe Macrophages Self-renewal stem cell biology regeneration infection molecular genetics genetic CRISPR Cas9 screen alveolar macrophages Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-ADG-2015 - ERC Advanced Grant Zaproszenie do składania wniosków ERC-2015-AdG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-ADG - Advanced Grant Instytucja przyjmująca TECHNISCHE UNIVERSITAET DRESDEN Wkład UE netto € 1 352 846,78 Adres HELMHOLTZSTRASSE 10 01069 Dresden Niemcy Zobacz na mapie Region Sachsen Dresden Dresden, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 352 846,78 Beneficjenci (2) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko TECHNISCHE UNIVERSITAET DRESDEN Niemcy Wkład UE netto € 1 352 846,78 Adres HELMHOLTZSTRASSE 10 01069 Dresden Zobacz na mapie Region Sachsen Dresden Dresden, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 352 846,78 CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Francja Wkład UE netto € 1 147 147,22 Adres RUE MICHEL ANGE 3 75794 Paris Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 147 147,22
