Für den Inhalt der Angaben zeichnet die Projektleitung verantwortlich.
This project is one of the five winners of the call 2014 «Rare Diseases - New Approaches».
Project partners: Clinical Center, National Institutes of Health, Bethesda, MD, USA; Centre for Molecular Medicine, Department of Pediatric Medicine and Surgery, CHUV, Lausanne
Förderbeitrag: CHF 250'000
Dauer: 05.2015 - 04.2017
Handlungsfeld: Rare Diseases, 2009 - 2014
Prof. Dr. Fabio Candotti
Lausanne University Hospital (CHUV)
Division of Immunology and Allergy
Rue du Bugnon 44, BU44 07/2308
1011 Lausanne (Schweiz)
- fabio.candotti@chuv. ch
Primary immunodeficiency diseases (PID) are a heterogeneous group of rare disorders that affect the immune system and cause an increased number of serious infections in affected individuals. Most patients affected with PID are identified in childhood, but an increasing number of conditions interfering with the normal function of the immune system are also discovered in adult individuals. About 250 forms of PID are currently known and while several conditions have easily recognizable clinical presentations, in many cases different diseases have overlapping and common clinical features. In addition, atypical presentations of well-known syndromes often complicate the clinical interpretation. Genetic analysis offers the possibility of establishing a definitive diagnosis, which is of paramount importance to make prognostic assessments and to provide patients and families adequate clinical management and genetic counseling. The objective of this project is, therefore, to establish a diagnostic platform that will allow to determine the genetic component that underlies the disease phenotype. A complementary objective of the project is to characterize the mechanisms of the immune systems that are affected by the genetic mutations, which will provide additional notions of how the immune system develops and works in health and disease.
Was ist das Besondere an diesem Projekt?
This project will take advantage of the recent revolution of genomic analysis brought about by the development of high-throughput, next generation sequencing (NGS) methods to perform screening of genes responsible for known forms of PIDs, as well as of candidate genomic regions that may be implicated in the pathophysiology of still undefined immunologic defects. Using cutting edge methods of molecular and cellular biology (e.g. CRISPR/Cas-9, iPS cells), this project will develop cellular models that recapitulate the immune defects observed in humans, which will inform the developments of new forms of therapies for PIDs.
We have identified 362 genes that are either known to be at the basis of or can be hypothesized to be associated with various forms of PIDs. A library of primers covering the coding sequences of such genes has been generated that results in around 5500 amplified sequences. This NGS platform will be validated using DNA samples from healthy control subjects and patients affected with known forms of PID. We foresee these milestones to be reached within the first quarter of 2016. Acquisition and testing of patient samples from clinical cases is ongoing. Cellular modeling of genetic causes of PID will begin the second quarter of 2016.
Am Projekt beteiligte Personen
Fabio Candotti, Professeur Associé UNIL fabio.
Stéphanie Georget-Droz, PhD, stephanie.
Elettra Santori, PhD Student elettra.
Davide Mercuri, Administrative Manager davide.
Letzte Aktualisierung dieser Projektdarstellung 17.10.2018