Obiettivo The aim of this project is to try to understand the complex molecular mechanisms involved in DNA editing, repair and recombination during immunoglobulin class switch recombination (CSR) and somatic hypermutation (SHM). We have developed a series of PCR-based assays to study in vivo generated CSR junctions and the pattern of mutations introduced in the immunoglobulin variable region genes in human B cells, allowing us to characterize CSR and SHM in patients with immunodeficiency due to defect(s) in DNA repair/recombination. Novel in vitro CSR assays, based on GFP expression, allowing quantitative measurement of substrate recombination, are also being developed. In addition, we have initiated an evolutionary analysis of the function and structure of activation-induced deaminase, an essential molecule involved both in CSR and SHM, aiming to identify CSR specific-cofactor(s). Combining these approaches, we will be able to define the DNA repair pathways involved in CSR and SHM. The suggested project requires access to patients with various defects in the DNA repair pathways. Many of these diseases are exceedingly rare. However, through worldwide collaboration, we have obtained samples from a majority of the diagnosed patients. We are also refining the existing screening methods and developing novel methods, that will allow identification of additional patients both with recognized and new diseases caused by mutations in DNA repair pathways. Finally, we hope to be able to address the question whether illegitimate CSR events are associated with predisposition to lymphomagenesis in patients with immunodeficiency/DNA repair defect(s), by analyzing the CSR induced chromosomal breaks and translocations in these patients. A large-scale sequencing project is also planned to characterize the CSRnome in B-cell lymphoma samples. Campo scientifico engineering and technologycivil engineeringstructural engineeringstructural health monitoringnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicineoncology Programma(i) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) ERC-SG-LS6 - ERC Starting Grant - Immunity and infection Invito a presentare proposte ERC-2009-StG Vedi altri progetti per questo bando Meccanismo di finanziamento ERC-SG - ERC Starting Grant Istituzione ospitante KAROLINSKA INSTITUTET Contributo UE € 1 888 166,00 Indirizzo Nobels Vag 5 17177 Stockholm Svezia Mostra sulla mappa Regione Östra Sverige Stockholm Stockholms län Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Qiang Pan Hammarström (Dr.) Contatto amministrativo Kim Von Schoultz (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Beneficiari (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto KAROLINSKA INSTITUTET Svezia Contributo UE € 1 888 166,00 Indirizzo Nobels Vag 5 17177 Stockholm Mostra sulla mappa Regione Östra Sverige Stockholm Stockholms län Tipo di attività Higher or Secondary Education Establishments Ricercatore principale Qiang Pan Hammarström (Dr.) Contatto amministrativo Kim Von Schoultz (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato