Ciliopathy Research Group

Group Leader: Colin A Johnson, Reader in Molecular Neuroscience

Molecular genetics of ciliopathies

In recent years, an ever-increasing number of inherited diseases, of previously unknown aetiology, are caused by defects in primary cilia and basal bodies. The aim of the Ciliopathy Research Group is to gain novel insights into the molecular mechanisms of early embryogenesis and neurodevelopment, by elucidating the role of primary ciliary and basal body function with key pathways of development.

My group identified mutations in the first gene, TMEM67, for a severe autosomal recessive malformation syndrome, called Meckel-Gruber syndrome (MKS) that is characterized by renal cystic dysplasia and central nervous system malformations (published in Nature Genetics, 2006). MKS is the most severe condition in a suite of developmental conditions known as “ciliopathies” that caused by defects in the structure or function of priamry cilia. We aim to understand the molecular pathogenesis of this disorder, and other ciliopathies such as Joubert syndrome (JBTS) with neurological or ophthalmological features.

Funding from a Sir Jules Thorn Charitable Trust annual Award for Biomedical Research has enabled us to develop a programme of work to identify new recessive disease genes. The aims of this resource are to recruit consanguineous families with an autosomal recessive condition for research studies. This enables novel disease-causing genes to be identified by using autozygosity mapping. Once a gene has been identified then accurate molecular diagnostic tests can be developed and translated into NHS service provision. This has immediate patient benefit, for local families that were originally recruited for the research, and for other families with the same condition that are referred for diagnostic testing by clinicians throughout the UK and the world. As a research grouping, we have identified a remarkable 30 recessive disease genes in just over three years, with many scientific insights gained into the normal processes of tooth formation, embryogenesis and eye development. A recent example is the identification of mutations in MEGF10 as a cause of the early-onset myopathy EMARDD (published in Nature Genetics, 2011).

Ciliopathy 2

All of the recent gene discovery work has relied on access to next generation sequencing and collaboration with a unique grouping of researchers and clinicians. Whole exome sequencing now allows disease-causing mutations to be quickly identified in a disease gene even without any initial mapping work, and we are using this approach for those families that have not previously been suited for traditional genetic mapping. This work has also enabled further grant funding from the Medical Research Council and the British Heart Foundation to pursue this gene discovery strategy. We are interested in identifying new genes for MKS and JBTS by using the strategy of autozygosity mapping and whole exome sequencing, but we will also continue the functional characterization of proteins localized to the ciliary transition zone, such as meckelin/TMEM67, an orphan receptor encoded by the TMEM67 gene. A particular interest in the medium term is to understand the genetic basis of the variability in clinical features (even within individual families) for the ciliopthies and autosomal dominant immunological conditions.

The Ciliopathy Research Group contributes to an EU FP7 Collaborative Project/Large-scale Integrating Project (“SysCilia”) for systems biology approaches to dissect cilia function and its disruption in human genetic disease at the molecular level. A major component of the “SysCilia” project has been the recent completion of a whole genome reverse genetics screen for genes that can contribute to ciliogenesis or cilia maintenance. The screen is based on automated visual recognition of cilia using a high-throughput high content imaging microscope. The major imperative for this research has been the estabishment of a "systems medicine" approach to collating and interoggating very large data-sets. This data includes hits from our reverse genetics screen, combined with sequence variants from human patients ("forward genetics"), with the aim of using the intergrated data-sets for diagnostic and prognostic clinical benefit.


Professor Colin Johnson – Group Leader, Reader
Dr Matthew Adams – Research Fellow
Zakia Abdelhamed - Post-Doctoral Research Fellow
Shabana Khan, Clinical Research Nurse
Dr Clare Logan - Post-Doctoral Research Fellow
Ms Subaashini Natavaja - Research Assistant
Mrs Katarzyna Szymanska - Research Assistant/PhD student
Dr Gabrielle Wheway - Post-Doctoral Research Fellow
Dr. Verity Hartill, Clinical Research Fellow
Ekram Shoaib, PhD Student
Ruth Hughes, PhD Student
Warren Herridge, Placement Student


Abdelhamed ZA, Wheway G, Szymanska K, Natarajan S, Toomes C, Inglehearn C, Johnson CA (2013). Variable expressivity of ciliopathy neurological phenotypes that encompass Meckel-Gruber syndrome and Joubert syndrome is caused by complex de-regulated ciliogenesis, Shh and Wnt signalling defects. Hum. Mol. Genet. 22: 1358-72.

Logan CV, Lucke B, Pottinger C, Abdelhamed ZA, Parry DA, Szymanska K, Diggle CP, van Riesen A, Morgan JE, Markham G, Ellis I, Manzur AY, Markham AF, Shires M, Helliwell T, Scoto M, Hübner C, Bonthron DT, Taylor GR, Sheridan E, Muntoni F, Carr IM, Schuelke M, Johnson CA (2011). Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nat. Genet. 43: 1189–1192.

Huang L*, Szymanska K*, Jensen VL*, Janecke AR, Innes AM,Davis EE, Frosk P, Li C, Willer JR, Chodirker BN, Greenberg CR, McLeod DN, Bernier FP, Chudley AE, Müller T, Shboul M, Logan CV, Loucks CM, Beaulieu CL, Bowie RV, Bell SM, Adkins J, Zuniga FI, Ross KD, Wang J, Ban MR, Becker C, Nürnberg P, Douglas S, Craft CM, Akimenko M-A, Hegele RA, Ober C, Utermann G, Bolz HJ, Bulman DE, Katsanis N, Blacque OE, Doherty D, Parboosingh JS, Leroux MR+, Johnson CA+, Boycott KM+.(2011) TMEM237, a novel protein associated with Joubert syndrome related disorder, expands the role of the TMEM family at the ciliary transition zone. Am J Hum Genet 89: 713-730 (* joint first authors, + joint corresponding authors).

Valente EM*, Logan CV*, Mougou-Zerelli S*, Ho Lee J*, Silhavy JL, Brancati F, Iannicelli M, Travaglini L, Romani S, Illi B, Adams M, Szymanska K, Mazzotta A, Eun Lee J, Tolentino JC, Swistun D, Salpietro CD, Fede C, Gabriel S, Russ C, Cibulskis K, Sougnez C, Hildebrandt F, Otto EA, Held S, Diplas BH, Davis E, Mikula M, Strom CM, Ben-Ze’ev B, Lev D, Sagie TL, Yaron Y, Krause A, Boltshauser A, Elkhartoufi N, Roume J, Shalev S, Munnich A, Saunier S, Inglehearn C, Saad A, Alkindy A, Thomas S, Vekemans M, Dallapiccola B, Katsanis N, Johnson CA+, Attié-Bitach T+, Gleeson JG+ (2010). Mutations in TMEM216, encoding a novel tetraspan protein, perturb ciliogenesis and cause Joubert (JBTS2), Meckel (MKS2) and related syndromes. Nat. Genet. 42: 619-625. (* joint first authors, + joint corresponding authors).

Smith UM*, Consugar M*, Tee LJ, McKee BM, Maina EN, Whelan S, Morgan NV, Goranson E, Gissen P, Lilliquist S, Aligianis IA, Ward CJ, Pasha S, Punyashthiti R, Malik Sharif S, Batman PA, Bennett CP, Woods CG, McKeown C, Bucourt M, Miller CA, Cox P, Algazali L, Trembath RC, Torres VE, Attie-Bitach T, Kelly DA, Maher ER, Gattone VH 2nd, Harris PC+, Johnson CA+, (2006). The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat. Genet. 38: 191-6. (* joint first authors, + joint corresponding authors).


British Heart Foundation, Clinical Research Training Fellowship (for Dr. Verity Hartill), lead supervisor “Congenital heart disease gene identification by whole exome medical resequencing". Aug. 2013-July 2016.

Newlife Foundation for Disabled Children, ; principal investigator, "Therapeutic interventions in preclinical animal models of severe ciliopathies". May 2013-Apr. 2015.

Medical Research Council, principal investigator, "Ciliopathy disease gene identification by whole exome medical resequencing". Feb. 2013-Jan. 2016.

Medical Research Council-DTG studentship, co-supervisor, "The role of MEGF10 in muscular dystrophies and myopathies". Oct. 2012-Sept. 2015.

Kid's Kidney Research, principal investigator, "Functional Characterization of Wnt signalling defects in mouse models of human ciliopathies". Sept. 2011-Aug. 2013.

EU FP7 “SysCilia” Collaborative Project / Large-scale Integrating Project for systems biology approaches for basic biological processes relevant to health and disease: “A systems biology approach to dissect cilia function and its disruption in human genetic disease”, principal investigator for University of Leeds work packages, June 2010-May 2015.

The Sir Jules Thorn Charitable Trust Award for Biomedical Research “An international resource for autozygosity mapping of autosomal recessive disease genes in consanguineous families”, principal investigator, Jan. 2010-Aug. 2016.


Competitive fully funded PhD scholarships are available within the Faculty Graduate School.

Self-funded students are always welcomed to apply for postgraduate study. International students must meet the entry requirements for English. Bench fees are required.

Please email for informal enquiries.

Related Links

Centre for Autozygosity Mapping

Ciliopathy Alliance UK