Publications

We report bi-allelic loss-of-function variants in OLA1 (Obg-like ATPase 1) as the cause of a novel neurodevelopmental disorder (NDD) characterised by intellectual disability, developmental delay, and joint hypermobility. This is the first study to link OLA1 to a neurodevelopmental disorder. Functional studies in C. elegans confirmed the pathogenicity of the identified variants, establishing OLA1 as a new disease gene and expanding our understanding of the molecular basis of NDDs.

Cranioectodermal dysplasia (CED) is a rare ciliopathy characterised by skeletal and ectodermal abnormalities, renal failure, and liver fibrosis. We identified a homozygous frameshift variant in CILK1 (encoding an ICK-related kinase that phosphorylates IFT-B components) as the causative mutation in a consanguineous family, expanding the genetic landscape of CED and confirming CILK1/DYF-5 as a disease gene through functional validation in C. elegans.

We describe a novel form of inter-ciliary communication called juxtaposed cilia-cilia elongation (JCE), in which adjacent cilia physically join tip-to-tip. Using C. elegans fluorescence imaging, we show that ARL13B (the Joubert syndrome GTPase) regulates JCE in a BBSome-dependent manner — loss of ARL-13 or BBS components abolishes joining, directly linking this process to ciliopathy-associated machinery.

We establish CC2D1A as a ciliopathy gene by demonstrating that loss of function causes a multisystem syndrome encompassing intellectual disability, heterotaxy, renal dysplasia, and abnormal cerebrospinal fluid flow. Functional studies in C. elegans and patient-derived data confirm pathogenicity, expanding the phenotypic spectrum of transition zone-associated ciliopathy genes.

CilioGenics is an integrated computational method that predicts novel ciliary genes by combining co-expression networks, protein–protein interactions, evolutionary conservation, and proximity to known ciliary loci. Published in Nucleic Acids Research, it recovers established ciliary genes with high precision while predicting new candidates — directly addressing the incomplete genetic diagnosis rate in ciliopathies.

We describe a CRISPR/Cas9-based pipeline for introducing patient-derived missense variants into the C. elegans orthologous gene to functionally distinguish pathogenic from benign variants. The approach — applied to ciliopathy genes including WDR31 and CILK1 — provides a rapid and cost-effective route to variant classification that complements computational prediction tools.

We identify WDR31 as a novel ciliary protein and show it acts redundantly with GTPase-activating proteins ELMOD and RP2 to regulate intraflagellar transport (IFT) complex assembly and BBSome recruitment. Triple mutants in C. elegans show severe IFT defects with accumulation of IFT-B components and impaired anterograde and retrograde transport, revealing a previously unknown layer of cilia entry regulation.

CiliaMiner is a manually curated database covering 55 distinct ciliopathy disorders with over 4,000 clinical manifestations and 507 disease genes. It classifies diseases as primary, secondary, or atypical ciliopathies based on symptom analysis and subcellular localisation data, and provides ortholog information across six model organisms including C. elegans, zebrafish, and mouse.

RPI-1, the C. elegans ortholog of human DCDC2 (a doublecortin domain protein associated with nephronophthisis), is shown to act redundantly with NPHP-4 (Nephronophthisis 4) in regulating cilia biogenesis. Single mutants show mild defects; double mutants display severe ciliary phenotypes, revealing a genetic interaction relevant to nephronophthisis pathogenesis.

A step-by-step protocol for using ConVarT to search for human missense variants at conserved positions in non-human model organisms. The protocol guides researchers through query construction, result interpretation, and integration with functional databases to accelerate variant prioritisation in rare disease genomics.

A detailed quantitative protocol for measuring intraflagellar transport (IFT) train speed and frequency in living C. elegans using TIRF microscopy. The method enables precise comparison of anterograde (kinesin-2 driven) and retrograde (dynein-2 driven) IFT kinetics in wild-type and mutant animals, and is directly applicable to studying ciliopathy gene function.

ConVarT is a web-based search engine that systematically matches human missense variants to equivalent positions in C. elegans, zebrafish, mouse, and other organisms. By enabling cross-species variant lookup, it dramatically accelerates functional prioritisation of variants of uncertain significance (VUS) identified from patient whole exome and genome sequencing.

MSABrowser is a lightweight JavaScript tool for interactive visualisation of multiple sequence alignments, genetic variants, and functional annotations directly in the browser — no installation required. It enables researchers to inspect conservation at patient variant positions across species and overlay experimental annotations, supporting variant interpretation workflows.

Tubulin glutamylation — a post-translational modification of the ciliary axoneme — is shown to respond dynamically to environmental stimuli in C. elegans sensory cilia via the p38 MAPK pathway. This finding links signal transduction pathways to ciliary tubulin code regulation, with implications for understanding how cilia adapt to external conditions.

Genome-wide prediction of G-quadruplex (G4) forming sequences in E. coli reveals a conserved structural switch between G4, hairpin, and duplex conformations at regulatory regions. This work identifies putative G4 motifs in bacterial genomes and provides a computational framework for studying non-B DNA structures as potential gene expression regulators.

The Joubert syndrome GTPase ARL13B is shown to be restricted to an Inv-like subdomain of the ciliary membrane by a combination of active anterograde transport and diffusion barriers at the transition zone. This compartmentalisation is essential for ARL13B function and represents a fundamental principle of ciliary membrane organisation relevant to Joubert syndrome pathogenesis.

Endocytosis machinery — classically associated with membrane internalisation — is shown to play an unexpected role in facilitating protein and membrane transport into C. elegans sensory cilia. This study reveals a non-canonical function for endocytic genes in ciliary membrane homeostasis and provides new insight into the mechanisms controlling ciliary membrane composition.

The AP-1 clathrin adaptor complex, canonically involved in intracellular vesicle trafficking, is shown to be required for cilium formation and to cooperate with the Rab GTPase RAB-8 in ciliary membrane transport in C. elegans. This work establishes a direct role for clathrin-mediated trafficking machinery in ciliogenesis.

The Joubert syndrome protein ARL13B is shown to localise to ciliary membranes and to stabilise IFT-mediated protein transport in C. elegans. Loss of ARL-13 disrupts ciliary membrane composition and IFT dynamics, providing the first in vivo functional characterisation of ARL13B in a genetic model organism and establishing C. elegans as a platform for Joubert syndrome research.

A comprehensive review of intraflagellar transport (IFT) — the bidirectional motor-driven movement of multi-protein complexes along the ciliary axoneme that is essential for cilia assembly, maintenance, and signalling. This early review synthesises molecular characterisation of IFT-A and IFT-B subcomplexes, motor proteins, and cargo, and frames the emerging connection between IFT defects and ciliopathies including Bardet-Biedl syndrome and Joubert syndrome.