Publications
Biallelic KIF24 Variants Are Responsible for a Spectrum of Skeletal Disorders Ranging From Lethal Skeletal Ciliopathy to Severe Acromesomelic Dysplasia
Reilly et al. together with our ESR (11) Alice Tata has identified mutations in gene KIF24, which encodes a kinesin family member controlling ciliogenesis. The six affected individuals had different levels of skeletal disorders and in vitro experiments showed that primary cilia assembly was severely impaired. This study is the first report implicating KIF24 variants as the cause of a skeletal dysplasia.
Biochemically validated structural model of the 15-subunit intraflagellar transport complex IFT-B
Petriman et al. together with our two fellows: ESR (1) Nevin Zacharia and ESR (13) Magdalena Georgieva has described structures of intraflagellar transport complex IFT-B. They we used Alphafold computation and designed model was validated using cross-linking/mass-spectrometry data on reconstituted IFT-B complexes, X-ray scattering in solution, diffraction from crystals as well as site-directed mutagenesis and protein-binding assays. This study bridges a gap in understanding of the IFT-B structure and allows for the mapping of ciliopathy variants in context of the IFT-B complex.
Primary cilia sense glutamine availability and respond via asparagine synthetase
Maria Elena Steidl from Alessandra Boletta’s group together with our fellow ESR (6) Anne Nielsen study how primary cilia sense available nutrients. They found out that primary cilia can adjust their length in response to nutrient availability via glutamine-mediated anaplerosis facilitated by asparagine synthetase (ASNS) localized at the base of the cilia. Ciliated cells respond to nutrient deprivation with cilia elongation and reducing glutamine-dependent mitochondrial anaplerosis which can be restored by glutamine supplementation. Their data indicate a role for cilia in responding to, and possibly sensing, cellular glutamine levels via ASNS during metabolic stress.
Generation of induced pluripotent stem cell line carrying frameshift variants in NPHP1 (UCSFi001-A-68) using CRISPR/Cas9
Our PhD fellow ESR (8) Emma Dyke has succesfully generated an induced pluripotent stem cell line carrying mutation in Nephrocystin 1 (NPHP1) gene with CRISPR/Cas9 technology. NPHP1 protein localizes to the transition zone of primary cilium and loss of NPHP1 function alters the structure of the transition zone and leads to defects in ciliary morphology, including decreased percentage of ciliation, altered ciliary length, and mislocalisation of ciliary proteins.
DLG1 functions upstream of SDCCAG3 and IFT20 to control targeting of polycystin-2 to the primary cilium
Our fellow Csenge Kata Rezi (ESR7) investigated a potential role of DLG1 in regulating ciliary composition in kidney epithelial cells. Her new article (currently available on BioRxiv) shows that DLG1 is a key component regulating ciliary trafficking pathway and intracellular trafficking into the primary cilium.
Interactome Analysis Reveals a Link of the Novel ALMS1-CEP70 Complex to Centrosomal Clusters
Unraveling protein networks inside and at the base of primary cilia is a key task of our fellow Shibu Antony (ESR 3). In this new article he has contributed to the study of interactome of ALMS1, protein associated with Alström syndrome. They revealed a key interaction of ALMS1 with CEP70 for ALMS1 stabilization at the basal body. This study provides candidate lists of ALMS1 interactors that might help in deeper understanding of ALMS1 in cilia-related functions.
Rare homozygous cilia gene variants identified in consanguineous congenital heart disease patients
Congenital heart disease (CHD) is a term for any cardiac defect present at birth. Multiple factors can contribute to the etiology of this disease, including genetic factors. New study (currently available on medRxiv) done by our fellow Daniel A. Baird (ESR 12) has studied the contribution of recessive genotypes in CHD. The analysis revealed involvement of ciliary genes and their indispensable role in cardiac septation.
Fluid shear stress triggers cholesterol biosynthesis and uptake in inner medullary collecting duct cells, independently of nephrocystin-1 and nephrocystin-4
Nephronophthisis (NPH) was the focus of interest of our fellow Giulia Ferri (ESR 10). During her PhD studies she contributed to the article investigating the role of NPHP1 and NPHP4 in the mechanoresponse to the fluid shear stress in renal epithelial cells. This study revealed a mild role of these proteins in flow sensation and uncovered a novel signaling pathway induced by shear stress.
Here you can find all publications such as research articles or reviews where our ESRs are authors (with the acknowledgement of the EU funding for the SCilS-ITN grant).