UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Professor Phil Beales

Telephone Number:  0207 905 2277



Phil Beales is head of Genetics and Genomic Medicine at ICH, Director of the Centre for Translational Genomics (GOSGENE) and head of the Cilia Disorders Laboratory (CDL). His research interests centre on rare diseases, especially the ciliopathies, a class of disorders caused by defects in the formation or function of the cilium.

This focus on ciliopathies stems from a long term interest in Bardet-Biedl syndrome (BBS) a genetically heterogeneous disorder characterized primarily by retinal degeneration, obesity, polydactyly and renal malformations. Following his medical training at King's College and UCL, Phil was drawn to research, initially into the genetics of diabetes, insulin resistance and obesity. He became interested in BBS with the idea that understanding the pathomechanism of this rare disease may give broader insights into more common disease etiology. In 2003 the CDL was instrumental in establishing primary cilia dysfunction as causative in BBS, a finding that was at the spearhead of the now thriving field of ciliopathy research.

A wide array of disorders characterized by a diverse yet overlapping range of phenotypes have now been shown to stem from ciliary dysfunction. As a result the research interests of the CDL have broadened beyond just BBS and our research now encompasses how and why ciliary dysfunction leads to the range of phenotypes observed across the ciliopathy spectrum. The emphasis of the lab has recently shifted towards translational science and we are now actively engaged in ciliotherapeutics to define targets that could be exploited for treatment of these debilitating conditions.

Main Interests/Achievements

The Ciliopathies

Traditionally our efforts have been concentrated on understanding the normal cellular and developmental roles of cilia proteins and how collectively they give rise to the phenotypes observed. To this end we have developed several tools including modelling the diseases in cell lines and model organisms such as Danio Rerio and Mus Musculus. We also continue to closely study the human BBS phenotype and have previously reported on the genetic epidemiology, natural history, novel phenotypes, genotype-phenotype correlation, and the behavioural and neurological aspects seen in this disorder.

In the years following our work linking BBS to cilia many phenotypically similar diseases were also found to be ciliopathies. However research done in this lab was the first to show that some chondrodysplasias are also caused by ciliary dysfunction. The finding that mutations in  the intraflagellar transport (IFT) component IFT80 were causative in JATD has led to the discovery of a whole class of skeletal ciliopathies including JATD, the short rib polydactyly syndromes, Sensenbrenner/CED and Mainzer-Saldino. Causative genes have now been found for most of these, the vast majority of which also encode components of the core IFT complexes. Work to define precisely how and why defects in IFT lead to the skeletal phenotypes observed in this class of ciliopathies is ongoing.

We also work on a range of other areas related to the ciliopathies which include:

• The role of transcription factors in regulating expression of cilia proteins

• The biology of cilia formation and intraflagellar transport

• The relationship of cilia proteins to intracellular signalling pathways

• The relationship between the cilium and the cytoskeleton

Most recently we have begun focusing on establishing therapies for the ciliopathies. We are actively engaged in a range of projects encompassing both drug based and gene therapy approaches to try and find novel treatment options for these conditions.

3MC Syndrome 

3MC syndrome is a rare recessive disorder comprising characteristic craniofacial patterning defects including cleft lip and/or palate, learning difficulties, umbilical and distal limb defects.  We recently positionally cloned two genes, COLEC11 and MASP1 both of which encode proteins with key roles in the lectin complement pathway.  We demonstrated that COLEC11 has chemotactic properties that regulate cell migration such as the neural crest cells during embryogenesis.  This study links for the first time complement components with developmental disorders and indicates how we may come to better understand craniofacial development. 

Early-onset syndromal and non-syndromal obesity

We maintain a strong interest in the genetics of early-onset obesity largely through the study and understanding of single gene disorders. Our approach is simply that by gaining a greater understanding of the genetics and biology of rare disorders such as BBS, Alstrom, Cohen, Albrights hereditary osteodystrophy and MOMO to name but a few, we can apply the common biochemical pathways to the more complex disorders.


This gene discovery facility was established in 2010 to provide comprehensive novel mutation detection in patients with orphan diseases. GOSGENE is funded by the Specialist Biomedical Research Centre (GOSHICH) and will fund as well as undertake the experimental work required for individual PIs/clinicians from diverse backgrounds who may not have the relevant genetics expertise. We use a wide range of techniques including traditional linkage, autozygosity mapping and increasingly Next Generation sequencing. We also undertake detailed analysis of NGS datasets using dedicated bioinformaticians. 



2014 - 2016 NIHR Translational Research Collaboration - Paediatrics Cross Cutting ThemeTitle: "Deep phenotyping in Bardet-Biedl and Alstrom Syndromes", Award: Joint with Prof Tim Barrett (BCH) - £465,000
2013 - 2016 Dutch Kidney Foundation, Title: "Combatting juvenile kidney failure in renal ciliopathies", Award: £314,993
2013 - 2015 NEWLIFE, Title: "Investigation of the role of the compliment pathway in 3MC syndrome and craniofacial development". Award: £120,000
2012 - 2015 Wellcome Trust Strategic Award/MRC contribution. Title: Human Induced Pluripotent Stem Cell Resource (co-applicant). Award: £12m to Sanger Institute/KCL (Durbin/Watt)
2010 - 2015 EU Framework Programme 7 - SYSCILIA. Title: Systems biology of the cilium and disease. Award: EURO 529,000 

Recently completed grants

2012 - 2014 Wellcome Trust Senior Research Fellowship in Clinical Science. Title: "Investigating the role of primary cilia in development and disease". Award: £332,000
2011 - 2013 NIHR (GOSH/ICH) Biomedical Research Centre. Title: Establishment of GOSgene - centre for gene discovery. Award: £565,000
2010 - 2011 NEWLIFE. Title: "Identification of two 3MC syndrome genes". Award: £10,500
2009 - 2012 Medical Research Council. Title: "The role of cilia in development of hyperinsulinaemia and insulin resistance". Award: £457,350
2009 - 2011 NEWLIFE. Title: "Defining molecular heterogeneity in ciliopathies". Award: £119,998
2007 - 2012 Wellcome Trust Senior Research Fellowship in Clinical Science .Title: "Investigating the role of primary cilia in development and disease" . Principal investigator/fellow: PL Beales . Award: £1,530,000