UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Dr Chiara Bacchelli


I lead a group focused on Translational Genomics and Stratified Medicine at UCL Institute of Child Health within the Centre for Translational Genomics - GOSgene. Funded by the Great Ormond Street Hospital Biomedical Research Centre of the NIHR, GOSgene opened in February 2010 to facilitate rapid gene identification in uncharacterised rare genetic diseases as part of the 'Molecular Basis of Childhood Disease' Theme.

My work and interest in genetics began during my PhD working on rare congenital disorders with Professor Peter Scambler (Molecular Medicine Unit, ICH). I then worked with Professors Bobby Gaspar and Adrian Thrasher in the Molecular Immunology Unit (ICH) on the genetic characterization of primary immunodeficiencies. After a period at the Institute of Cancer Research working in the Section of Cancer Genetics lead by Professor Nazneen Rahman, I returned to UCL to facilitate the formation of GOSgene.

During the course of my career I have acquired a vast repertoire of molecular genetic techniques with focus on disease gene identification through linkage analysis, homozygosity mapping and next generation sequencing. My current work in GOSgene focuses on the use of exome and whole genome sequencing approaches coupled with advanced data analysis to deliver diagnostic tools for rare diseases. These will be tools for gene identification in affected individuals to help improve diagnostic testing, genetic counselling, family planning options, prenatal service development and personalised healthcare.

Main Interests/Achievements

My two main research areas of interest are rare diseases research and developing strategies for delivering stratified and precision medicine.

Rare Diseases Research. There are over 6,000 known rare diseases, often life-threatening or chronically debilitating. Collectively rare diseases are not rare and they affect 350 million people worldwide. In the UK, 1 in 17 people will be affected by a rare disease at some point in their life. This amounts to approximately 3.5 million people affected in the UK. 75% of rare diseases affect children and are often of genetic origin but only a quarter has a definitive molecular cause identified. Usually there is no effective treatment, but screening for early diagnosis, followed by suitable care, can improve quality of life and life expectancy.

The aim of my research in GOSgene is to accelerate the identification of yet unknown pathogenic genes in rare diseases by implementing the latest next generation sequencing technology. This research is critical to understand the pathophysiology and natural history of rare diseases, to identify potential therapeutic targets, discover new biomarkers, and ultimately adequately evaluate treatments and therapies.

Personalised Medicine is the next generation of medicine and healthcare research with the potential to provide significant benefits to patients and effect strategic shifts in the way healthcare is delivered in the clinic. Personalised medicine uses an individual's genetic profile to guide decisions made in regard to the prevention, diagnosis, and treatment of a disease. Developing new diagnostic tests and expanding the use of biomarkers enabling the identification of the molecular cause of a disease will ultimately support the development of novel more precisely targeted treatments. It has been estimated that only 30-70% of patients respond positively to drugs. Stratifying in advance groups of patients who have a greater likelihood of responding to a particular therapy or avoiding adverse effects based on their unique genetic and environmental profiles is the aim of personalised (or stratified) medicine.

Approaches implemented:

- Development of new diagnostic tests utilizing whole exome, whole genome or targeted gene panels sequencing

- Patient stratification strategies based on individual's genotype

- Advance bioinformatics tools for big data analysis

- Identification of biomarkers for precision medicine implementation

- Integration of -omics data

- Development of companion diagnostic tests


Our research team GOSgene has thus far studied 179 families that are drawn from 62 different rare disease clinical phenotypes. Exome sequencing in >400 samples has been performed. A number of these projects are at present on-going but so far we have been able to identify 41 causative genes (66% success rate). Of these candidate genes, 24 (58%) are novel genes, never been described before to be associated with disease.

Grants (last 5 years/Current)

2013 - 2017NIHR Biomedical Research Centre - Fellowship in Translational Genomics and Stratified Medicine awarded to Dr Chiara Bacchelli
2012Daniel Courtney Trust Charity; Principal Investigators: N Shah, C Bacchelli. Project title: "Exome sequencing in patients with microvillus inclusion disease" 
2010Biomedical Research Centre - Experimental research; Principal Investigator: K Gilmour, Co-investigators: HB Gaspar, C Bacchelli, N Lench, CN Cale. Project title: "Development of a next generation sequencing assay to screen children for twenty genes known to cause severe combined immunodeficiency (SCID)"