Personalised genomic medicine moves closer with the opening of Molecular Pathology Laboratories

Imperial College London scientists are making major progress in the field of genomic medicine, thanks in part to a state-of-the-art facility that officially opens today. - News

by Sam Wong
Wednesday 25 May 2011

Imperial College London scientists are making major progress in the field of genomic medicine, thanks in part to a state-of- the-art facility that officially opens today. The Molecular Pathology Laboratories, located on the College’s Hammersmith campus, are equipped with two “next generation” genetic sequencing machines, allowing dramatic improvements in the scale and speed at which researchers can sequence DNA.

Genome technologies have advanced extraordinarily in the past five years, with sequencing capacity increasing 1,000-fold and costs falling by a factor of 10,000. The latest generation of sequencing machines enable an entire human genome to be sequenced within 10 days for less than £10,000.

Imperial’s next generation machines have been in place since June 2010. Imperial researchers, in partnership with clinicians at Imperial College Healthcare NHS Trust, are already using the new machines to pinpoint faulty genes in patients with cardiomyopathy – a disease of the heart muscle. Cardiomyopathy often runs in families, but the disease can be caused by mutations in any of a large number of genes. Tracking down the mutation responsible in a particular family could previously have taken many years, but now scientists can do so in months or weeks. Once the faulty gene has been identified, family members can be easily screened to find out if they will develop the condition later in life.

High throughput sequencing is also helping researchers to find genetic causes of familial hypercholesterolaemia, which affects around one in 500 people in the UK and causes early heart disease.

“The potential of genome science to have a major impact in medicine has been recognised since the completion of the Human Genome Project more than 10 years ago,” said Professor Tim Aitman, Chair of the Molecular Pathology Group. “Now sequencing technology has reached a critical point where the opportunities for translating the science into better individualised patient care are growing exponentially.

“The new machines sequence about five times as much DNA as previous platforms. It’s a huge increase in ability, with little increase in cost.”

Genetic diagnosis is also expected to have an important impact in cancer treatment. It is increasingly recognised that mutations in certain genes influence which drugs individual patients are likely to respond to best. For example Herceptin, which is used for treating breast cancer, only works in patients who have mutations in the ErbB-2 gene.“Through genetic diagnostics we’ll increasingly be able to catalogue mutations which cause specific cancers and tailor treatment to the individual patient,” added Professor Aitman.

The development of the new laboratories began in October 2009, when the Molecular Pathology Group at Imperial were awarded a £2 million grant from the National Institute of Health Research (NIHR) to equip and refurbish a new laboratory in G block on the College’s Hammersmith campus. This funding enabled the group to invest in two “next-gen” machines, the HiSeq 2000 and the GS Junior, both of which were the first of their type to be installed in a UK research institution.

Genetics and Genomic Medicine is one of four cross-cutting research themes in the Imperial cBRC.

Research projects in the new labs are being funded by the Imperial Comprehensive Biomedical Research Centre (cBRC), a partnership between the College and Imperial College Healthcare supported by a major award from the NIHR. Genetics and Genomic Medicine is one of four cross-cutting research themes in the cBRC.

The HiSeq 2000, manufactured by Illumina, can sequence a whole human genome in two weeks, which helps clinicians and researchers to effectively diagnose and treat patients by examining which illnesses they are genetically predisposed to developing. It should also improve diagnosis of inherited conditions such as sudden cardiac death syndrome, by allowing scientists to sequence all of the patient’s susceptibility genes, rather than the one or two genes most likely to cause the condition. The second sequencer, GS-Junior, manufactured by Roche, can sequence long stretches of DNA in just 16 hours, therefore enabling rapid diagnosis in cases such as infectious diseases.

In addition to these, a Genome Analyser IIx and a further HiSeq 2000 are now available in the MRC Clinical Sciences Centre Core Genomics laboratory, and a SOLiD 4 sequencer has been installed on the Brompton Campus, giving Imperial scientists unprecedented access to top-of-the-range sequencing technology.

The massive volume of data generated by the new machines require high performance computers, sophisticated software algorithms and expert computational scientists to interpret the sequence data. Imperial, in partnership with the MRC Clinical Sciences Centre, has invested heavily in the infrastructure and expertise needed to translate sequence data into clinically useful information.

To mark the official opening of the new laboratories, the Molecular Pathology Group is hosting a mini-symposium today, with talks by Imperial speakers including Professor Jonathan Weber, Director of Research in the Faculty of Medicine; and the Rector, Sir Keith O’Nions; as well as distinguished guests including former health minister Lord Warner.