H2020Индивидуална стипендия2020–2022

xenCAKUT · CRISPR/Cas9 based kidney disease modeling to elucidate novel genetic drivers and therapeutic targets in X. tropicalis

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2020-10-01 → 2022-09-30
Финансиране от ЕС: 191 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Генетичните причини за вродени дефекти на бъбреците и пикочните пътища се изучават чрез моделиране с жаби Xenopus tropicalis. Това помага за разбирането на механизмите зад детските и възрастни бъбречни заболявания, които натоварват европейните здравни системи.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

CRISPR/Cas9 based kidney disease modeling to elucidate novel genetic drivers and therapeutic targets in X. tropicalis

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) collectively refer to a diverse group of malformations occurring during embryonic kidney and urinary tract development which underlie a major percentage (40%) of paediatric end-stage renal disease (ESRD) cases. CAKUT is also significant contributing factor to chronic kidney disease (CKD) in adults. CKD is becoming an increasing challenge for the European healthcare systems as it is estimated that between 3.3% and 17.3% of the EU population has reduced kidney function and is at high risk of becoming dependent on renal replacement therapies. In xenCAKUT, we intended to yield insight in the genetics of kidney disease using the amphibian animal model xenopus tropicalis.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

CRISPR/Cas9 has untapped potential for disease modeling in the diploid amphibian model organism Xenopus tropicalis (X. tropicalis). Here, I propose to employ state-of-the-art CRISPR/Cas9 technologies (in vivo CRISPR Screening, ShCAST, CRISPR-NSID) to address two current unmet clinical needs in congenital anomalies of the kidney and urinary tract (CAKUT). First, I will generate a novel animal model for autosomal dominant polycystic kidney disease (ADPKD) and investigate the role of a potential new druggable therapeutic target (ALDH1A1). Second, I propose to couple CRISPR screening methods to classical Xenopus animal cap differentiation assays to identify genes essential in the differentiation of pluripotent precursor cells towards pronephric structures. I intend to perform in vivo validation of hits to identify genes which underlie CAKUT development in X. tropicalis. Because a molecular diagnosis for CAKUT can currently only be made in about 20% of the clinical cases, the further elucidation of underlying genetic causes for CAKUT is of major clinical relevance. In vivo validated Xenopus CAKUT disease causing genes will be integrated with clinician networks (ERKNet, NEOCYST). This interdisciplinary approach will use well-established techniques from developmental biology, state-of-the-art CRISPR/Cas9 approaches, light-sheet-microscopy and machine-learning based phenotyping protocols to model common genetic forms of kidney disease using the diploid vertebrate model X. tropicalis.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT ZURICH · ZurichКоординаторШвейцария