N.L. prepares to raise the bar in bench-to-bedside genomics

Published: June 21st 2022

The pieces are coming together that could soon make Newfoundland and Labrador a leader in bench-to- bedside genomics, with the capacity to attract significant research and to change the lives of many Canadians and others with genetic-based disorders.

Central to this vision, doggedly pursued for a decade by molecular geneticists, Drs. Darren O’Rielly, at Eastern Health, and Terry-Lynn Young, at Memorial University of Newfoundland, is the new multimillion-dollar Centre for Translational Genomics in St. John’s. A joint initiative by Eastern Health and Memorial University, the CTG will be operated by Eastern Health.

For two molecular geneticists, Dr. Terry-Lynn Young, Memorial University of Newfoundland and Dr. Darren O’Rielly, Eastern Health, the new Centre for Translational Genomics is a dream come true for their home province, Newfoundland and Labrador.

The CTG’s suite of gene sequencing equipment, housed in the university’s medical school, is now undergoing validation. The star of the impressive collection is an Illumina NovaSeq 6000, the highest throughput second-generation sequencer on the market. 

Dr. O’Rielly, now the centre’s director, expects all systems will be firing by fall, or early next year, for a phase-one focus on hereditary diseases.

When it comes to capability, he said, “We have a full gamut for a comprehensive array of services to both researchers as well as clinicians,” he said.

When fully operational, the CTG, will offer clinical germline and somatic testing, in addition to a range of different sequencing options. Germline mutations are inherited while somatic ones are not. Somatic testing is usually done on tumors, often to provide personalized care.

No longer will the majority of samples have to be shipped outside the region for sequencing and analysis. This change alone, once the CTG is fully functioning, promises faster turnaround times for researchers, clinicians and patients.

Primarily conceived as a Newfoundland and Labrador enterprise, the centre has a close secondary aim to serve Atlantic Canada. To help realize the project, Genome Atlantic supplied a letter of support to tap the Atlantic Canada Opportunities Agency’s (ACOA’s) Atlantic Innovation Fund.

In addition, Genome Atlantic accessed its Genomics Opportunity Review Program to fund a business case assessment to support the ACOA submission. “That was really helpful,” said Project Co-Lead, Dr. Young. “It gave both us and our funders, and the institutions involved, confidence that what we were building would actually have clients at the end of the day, besides just Eastern Health – just the health care providers.”  

Funding for the CTG came from the Atlantic Canada Opportunities Agency, via its Regional Economic Growth Through Innovation program; from the Government of Newfoundland and Labrador, through the Department of Industry, Energy and Technology; and from the Health Care Foundation of Newfoundland and Labrador, as  well as the Janeway Children’s Hospital Foundation, the Dr. H. Bliss Murphy Cancer Care Foundation, Eastern Health and Memorial University of Newfoundland.

“In phase two, which is focused on sporadic diseases that includes most cancers,” Dr. Rielly explained, “there is an opportunity to partner with several of the different big pharma companies. And there’s also other companies in this realm, within Atlantic Canada, that have expressed an interest and willingness to use our centre as well.”

Generating researcher interest in the new centre should pose few difficulties, given the province’s extensive population of genomic isolates – that is, inhabitants separated into distinct groups that have historically avoided genetic mixing through intermarriage for various reasons, including geography. Sometimes referred to as Newfoundland’s founder population, it includes the province’s indigenous residents and those whose trace their ancestry to the European settlers. For anyone in genetic research, this is a dream population begging for study.

Equally attractive will be integrated research and clinical services, a key objective that Drs. O’Rielly and Young are working hard to facilitate.

They are hoping to significantly cut the time between the discovery of a gene-caused medical condition and the clinical response, by periodically re-analyzing sequencing data on patients. This would be done as new knowledge is translated from peer-reviewed research in the literature and in-house data confirm a genetic variant to be the source of a specific medical disorder. The move would end the need for multiple retests and shave years off the current gap between gene discovery and clinical action.

Dr. Young traces the impetus for the CTG to her experience with Arrhythmogenic Right Ventricular Cardiomyopathy or ARVC, a genetic heart disease that can trigger sudden death. It affects a great many Newfoundlanders and Labradorians, and in 2008 Dr. Young and her colleagues chased the cause to a single mutation on a single gene, TMEM43.

The potential hit home, she said, “once we realized if we could connect both the research side and the diagnostic side…we could really make a huge impact.”  They connected those dots and today, a simple blood test can diagnose ARVC, and an implanted defibrillator can protect sufferers from cardiac death.

With the centre established, work is now focused on generating projects, building networks of researchers and bioinformaticians as well as partnerships and collaborations to actualize their vision of a centre for Canadian excellence in translational genomics. Work is proceeding apace on all fronts.

“We’ve got a huge project now with the Terry Fox Institute Marathon of Hope Initiative, where they’re looking at all the different types of mutations that happen to single genes and to many genes within tumors, cells and tissues,” said Dr. Young. “All the Atlantic provinces are working together as one node,” Dr. O’Rielly said. The massive project is being divided up among different institutions in the region to keep the work in Atlantic Canada, he added.  The Atlantic node of the initiative is Dr. Sherri Christian, Department of Biochemistry, Memorial University of Newfoundland.

Collaborations and partnerships have already been established with colleagues at the IWK Health Centre in Halifax, N.S. Dr. O’Rielly said they are looking at common challenges, sharing resources and datasets, as well as working to establish common practices, so that the CGT can eventually process samples from the IWK seamlessly and the two organizations can provide backup for each other.

Undoubtedly, the centre will be a regional asset, but the major beneficiaries are expected to be Newfoundlanders and Labradorians, due to their close proximity to the CTG and their ease of access to the new services provided through Eastern Health. Research on the province’s genetic isolates, which includes most of its residents, is also expected to grow exponentially now because of the CTG.