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The Centre for Phenogenomics (TCP) – accelerating discoveries from nose to tail

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TCP is a world-class facility owned and operated by The Hospital for Sick Children and Mount Sinai Hospital. It opened in 2007 and has transformed strategic investments by the Hospitals, the Canada Foundation for Innovation (CFI), and Genome Canada into a unique national resource to provide critical tools (mouse and more recently rat models) and services that enables biomedical research of the highest caliber across the country. State-of-the-art infrastructure and technologies are combined at TCP to support excellent research and help companies succeed. TCP was designated a national research facility by the CFI in November 2014, and a Genomics Innovation Network Node by Genome Canada in April 2015. TCP is also a founding member of the International Mouse Phenotyping Consortium which was recognized as a distributed global infrastructure by the G7’s Ministers of Science in 2017.

TCP’s facility is uniquely programmed to design, produce, manage, analyze, and distribute mouse models to enable hypothesis-driven discovery, purpose-drive translational studies, and preclinical bioavailability, safety, and effect evaluation for therapeutic discovery. Quality assurance of processes and quality control of data and products is a priority at TCP. The Model Production Core provides services for embryonic stem (ES) cell- and Cas9 RNA-guided nuclease (Cas9 RGN) genome editing-derived mouse and rat production, genetic quality control, and colony management to deliver experimental cohorts. TCP is licensed to provide Cas9 RGN to academic and industry researchers so the customer is able to use the model. The Clinical Phenotyping Core provides services for comprehensive or customized user-focused analysis of gene function, mutant gene dysfunction, or validation of drug target and evaluation of treatment effect across diverse areas of biology, disease, or therapeutics in mice. This Core uses non- or minimally invasive phenotyping tests to identify abnormalities. The Pathology Core provides services for necropsy, gross pathology, histology, immunohistochemistry, semi- and quantitative image analysis, and histopathology to correlate genetic or compound-associated changes with tissue structure and disease. The Cryopreservation & Recovery Core provides state-of-the-art embryo, ES cell, and sperm services, and global acquisition and distribution so customers can get the models they need and access secure and convenient storage and distribution of their rodent models. All data generated from each of the Cores belongs to the customer.

Recently, TCP expanded to establish the Infection & Inflammation Core directed by Dr. Silvia Vidal at McGill University. Dr. Vidal is globally recognized as an expert in the genetics of susceptibility and resistance to infection. A purpose-built Biosafety Level 2 and Biosafety Level 3 facility, this Core extends TC P’s services to enable genome-wide assessment of genes and variants associated with resistance or susceptibility to infectious disease. Colonization with bacterial, viral, fungal, or parasitic agents is available to model host response to infection and explore preventative or therapeutic proof-of-principle. Antigen-induced inflammatory disease models are also available to users to assess host response to in vivo immunological challenges such as neuro- or intestinal inflammation.

TCP is supported by its multidisciplinary Informatics Team that provides web-enabled access for users (on-line requests, service descriptions, service fees, guidelines, reports) and the informatics software, databases, infrastructure, and interfaces necessary to support TCP’s operation. A Senior Biostatistician was recently recruited to provide study design and statistical analysis services using available software tools and approaches or developing bespoke methods if needed by the customer.

TCP’s mission is to help you with your research whenever we can add value. The facility’s Services Coordinator provides pre-sales support, information flow, project coordination, timely and complete access to data, and post-delivery follow-up to users. To find out more, go to TCP, or email services@phenogenomic.ca.

Precision Health Initiative – Rare Diseases: Clinical Implementation Projects

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Genome Canada has launched a national initiative for the clinical implementation of precision health, focusing on a rare disease pilot program as a foundational step. This initiative features three main components:

  1. A national rare disease cohort is envisioned to be established through the collection and sequencing of 30,000 samples from rare disease patients and their families.
  2. A national platform is being set up to provide mechanisms and best practices for the collection and sharing of data, including privacy policies, informed consent and other ethical and legal frameworks.
  3. Clinical implementation will advance through working with provincial and regional centres and partners to establish clinical sites and achieve regulatory approval and accreditation.

In order to initiate this ambitious program, Genome Canada is encouraging the submission of projects to the Genomic Applications Partnership Program (GAPP) that will translate research into clinical implementation with the goal of having genome sequencing offered as a clinical genetic test within an established diagnostic and clinical care pathway for rare diseases. The other activities in the Precision Health Initiative – Rare Diseases will be advanced through other funding mechanisms.

Eligibility Criteria

  1. Applications will be required to meet the eligibility criteria for GAPP funding in general. That is, projects must:
  • develop and apply a genomics-derived tool, product or process to an opportunity or need defined by the Receptor(s);
  • focus on late stage R&D that will position the innovation for near term implementation / commercialization;
  • be co-led by an Academic and a Receptor organization in partnership, with active and necessary roles for both; and,
  • have the potential to generate significant social and/or economic benefits for Canada.

The GAPP Guidelines provide full information on eligibility.

Furthermore, in order to be considered eligible as a Rare Diseases Clinical Implementation Project, projects must also:

  • focus on using precision health approaches in rare diseases that are ready to be implemented in partnership with an existing publicly funded health care delivery organization (at the provincial or regional level that has the technological and organizational infrastructure needed to support the project).  The organization should have the capabilities to implement clinical and laboratory workflows; install or upgrade local informatics systems linked to a central data repository; and, validate/benchmark technology platforms.
  • analyze province specific health technology assessment data to determine the clinical utility, cost utility and cost effectiveness of genomic sequencing.
  • commit to working with other rare disease clinical implementation projects funded through this mechanism to share best practices and harmonize data capture.
  • commit to data sharing, data standards, consents and other policies that comply with the guidelines for the overall initiative and are consistent with the principles and policies of the Global Alliance for Genomics and Health, the International Rare Diseases International Research Consortium and the FAIR Guiding Principles for scientific data management and stewardship.

For more information, please contact Helen Petropoulos, Director, Commercialization & Programs.

Celebrating the microbes in, on and around us!

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Microbes help support all life on our planet.  Although invisible to the naked eye, our survival depends on them.

Microbes are the trillions of microorganisms – bacteria, viruses, fungi, protists, archaea and algae – found in and on every living thing, such as in our gastrointestinal tract, or in a plant, or in the soil surrounding a plant. Different species of microbes form diverse and complex communities, and when combined with a host or environment, that microbial ecosystem is called a microbiome.

Microbiomes affect our lives in many ways.  For example, microbial ecosystems help recycle nutrients in soil needed by crops, break down pollutants and provide much of the oxygen we breathe, and help humans and animals digest food and ward off disease.

Ontario Genomics is proud to support scientific teams across Ontario and their cutting edge microbiome research in Canada’s health, agriculture, bioproducts, water and mining sectors.  To learn more about their amazing work and how it’s helping to drive healthier lives, a healthier planet, and healthier economies, check out the projects featured below.

Combating crop disease without pesticides
Project Leader: Dr. Manish Raizada (University of Guelph)
News_20180627_MicrobiomeDay-01Some of the most serious fungal pathogens affecting corn enter the grain through the sperm-transmitting channels of the silks, leading to hundreds of millions of dollars in cumulative crop losses in Ontario and Canada, as well as the accumulation of toxins in the grain that affect the health of both humans and livestock. Manish N. Raizada’s lab at the University of Guelph is working to discover probiotic microbes that seek and destroy harmful pathogens which can be applied to combat the crop diseases afflicting grain farmers, reduce reliance on pesticides, and build more sustainable and effective industry practices. Learn more

Eliminating harmful bacteria for food safety & health
Project Leaders: Dr. David Edgell & Dr. Gregory Gloor (University of Western Ontario)
News_20180627_MicrobiomeDay-02Dr. David Edgell and Dr. Gregory Gloor of the University of Western Ontario are working to develop and test a novel microbial control system to enable the selective elimination of individual bacteria from a mixed population of bacteria. Their dual nuclease-based CRISPR microbial control system has broad-ranging applications in biomedical research, industrial food-related processes, and human health. Learn more

Personalized medicine & drug efficacy for IBD patients
Project Leaders: Dr. Alain Stintzi (University of Ottawa), Dr. David Mack (Children’s Hospital of Eastern Ontario), in partnership with Biotagenics
News_20180627_MicrobiomeDay-03The more than 1,000 different species of bacteria that colonize our gastrointestinal tract are collectively known as our microbiome. Alain Stintzi and David Mack are working in partnership with Biotagenics to design simple and quick tests to reveal the optimal treatment for IBD patients. Their work will enable personalized treatment plans based on each patient’s characteristics and can be used to easily monitor each patient’s progress and modify treatment plans if needed. These tests will help clinicians use the right drug at the right time for the right patient. Learn more

Understanding the impact of antibiotics for neonatal intensive care
Project Leaders: Dr. Michelle Science (SickKids)& Dr Bryan Coburn (University Health Network)
News_20180627_MicrobiomeDay-04Michelle Science at SickKids and Bryan Coburn from the University Health Network are utilizing Ontario Genomics’ SPARK program to discern the impact of antibiotic use on the microbiome of the vulnerable neonate population during a critical period of development. The results of their work will provide important information to guide decision-making and prescribing practices for infants and neonates in health care facilities to improve patient outcomes. Learn more

Improving groundwater remediation
Project Leaders: Dr. Elizabeth A. Edwards & Dr. Radhakrishnan Mahadevan (BioZone at the University of Toronto)
News_20180627_MicrobiomeDay-05Most microbes in the environment live in close association with one another in mixed communities. These communities maintain high levels of complex interactions exchanging nutrients, vitamins and other chemicals. Through Ontario Genomics’ SPARK program, Elizabeth Edwards and Radhakrishnan Mahadevan of BioZone at the University of Toronto are developing computational models to not only boost the efficiency of dechlorination in groundwater remediation, but also to pave the way for other applications in complex microbial communities such as in the human gut and in deep marine sediments. Learn more

Reducing sulphur contamination in mining wastewaters
Project Leaders: Dr. Lesley Warren (University of Toronto), Dr. Jillian Banfield (UC Berkeley)
News_20180627_MicrobiomeDay-06Mining wastewaters contain sulphur compounds which can cause toxicity. An international team led by Lesley Warren at the University of Toronto and Jillian Banfield at the University of California, Berkeley is applying genomics, geochemistry and modeling to develop innovative monitoring, management and treatment tools. These innovations will safeguard the quality in receiving waters, better monitor, manage and reduce toxicity, and generate new tools to support cost-benefit decision-making. Learn more

Competitive Dairy Production
Project Leader: Dr. Gisele LaPointe (University of Guelph) in partnership with Parmalat
News_20180627_MicrobiomeDay-07Gizele LaPointe and her team at the University of Guelph have partnered with Parmalat Canada to better understand the microbiota of cheese and increase its manufacturing capacity using metagenomic, metaproteomic and metabolomics tools to meet the requirements of cheddar cheese production. These innovations will improve manufacturing processes and controls, significantly increase production capacity of high quality aged cheese, and increase revenues for dairy farmers. Learn more

Website: www.WorldMicrobiomeDay.com
Twitter: @WMicrobiomeDay
Hashtag: #WorldMicrobiomeDay
Instagram: WorldMicrobiomeDay
Facebook: www.facebook.com/WorldMicrobiomeDay

SynBio is booming at Western University

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Synthetic biology is an exciting discipline that sits at the crux of the intersection between design, biology, computing and manufacturing. This emerging field applies the “Design-Build-Test” principles of engineering to biology and leverages all that has been discovered through genomic studies and DNA sequencing.
Recently, Western University announced that it will be starting degree programs in synthetic biology at both the undergrad and graduate levels. In large part, these programs have been made possible thanks to the support of Western University’s Interdisciplinary Development Initiatives (IDI) Program – which provides seed funding for projects that further the university’s research and teaching mission, attract scholars and graduate students and bring it prestige.
We spoke to the team that spearheaded the initiative – David Edgell, Kathleen Hill & Bogumil Karas (the “IDI Team”) – to find out more about what Western’s synthetic biology (SynBio) program hopes to achieve.

What does the SynBio community look like at Western?
What you notice first about the SynBio@Western community is the enthusiasm, growth and diverse membership. You can find SynBio researchers in many different faculties (Science, Medicine & Dentistry, Engineering and Arts and Humanities). What caught our eye at the very beginning was the number of students engaged in synthetic biology. These students were looking for more opportunities for academic training and research experience in this broad field. We also noticed industry requests for student training in research and business in the synthetic biology field. We recognized that there is key expertise within the community at Western in designing microbes and applying synthetic biology approaches to agriculture and health sectors. We saw a need for the development of student training in this important area.

What led to successfully securing IDI Program support for synthetic biology?
There were a number of pieces in place that helped with the application. First, the student engagement, faculty research expertise, environment of collaboration at Western, the recent development of professional graduate programs, the greater engagement with industry and the entrepreneurial spirit and experience at Western set up a fantastic context to assemble a structure to formally enable student training in SynBio. Second, our researchers have also taken the SynBio discoveries to the lecture halls and redesigned courses to encompass interdisciplinary learning in this field. We have enjoyed collaborative teaching with faculty in the Sciences, Medicine and Arts and Humanities. There has been growth in student clubs and communities in genetics, ethics and synthetic biology. Third, we have been enjoying the growth in our seminar series and annual symposium that have helped raise the profile of SynBio research across campus. In addition, we already have a SynBio start-up (Designer Microbes Inc.) operating from Western’s incubator, The Stiller Center, which hopefully will inspire more students to start up their own companies after graduation. Continued funding successes in synthetic biology projects are adding fuel to the individual and collaborative research programs, and are also helping to raise the profile of synthetic biology at Western. We would also like to acknowledge and thank Ontario Genomics for its support of synthetic biology – which helped contribute to the success of Western University’s IDI proposal.

Why is the IDI program a good fit for synthetic biology?
The underlying motivation behind the IDI program at Western is to promote research and teaching initiatives that involve the participation and collaboration of individuals across discipline boundaries. Synthetic biology by its nature is interdisciplinary, encompassing research and teaching from genetics, biochemistry, engineering, computational biology, and ethics. Thus, the goals of the SynBio@Western proposal were perfectly aligned with Western’s vision for interdisciplinary initiatives. Moreover, the research and academic community in synthetic biology at Western were already developing into an example of what is envisioned in the IDI program. The IDI program at Western has an established record of success for providing a framework and structure that nurtures new initiatives through their early years, and providing funding in areas that are difficult to fund over multiple years through traditional granting mechanisms.

What outcomes do you hope to achieve by the end of the funding period?
We will see a collaborative graduate research program, scholarship awards that will support undergraduate and graduate research, the ability to bring high-quality scientists to Western for a Synthetic Biology seminar series, and support to continue the annual Synthetic Biology Symposium at Western.

Are there other SynBio degree-granting programs in Canada or abroad?
Synthetic biology is a rapidly growing field and yes, in our research, we identified different communities that are developing in Canada and globally. Degree programs are not numerous and so this initiative is really in the first wave of formal training programs, and we have the opportunity to make a unique path in student training. Currently under development for September 2019 is an undergraduate degree program in Synthetic Biology that will be jointly hosted by the Departments of Biochemistry and Biology at Western that will provide students with formal classes in synthetic biology as well as opportunities to participate in synthetic biology research projects.

Now in its third year, tell us about Western’s annual SynBio Symposium
The Synthetic Biology Symposium 3.0 is coming up on Thursday July 26, 2018 on Western’s campus. The Symposium, initially organized by Murray Junop, started as way to encourage interest and collaboration in synthetic biology research at Western. The first symposium was a resounding success, and it helped with the recruitment of Bogumil Karas to Western from the J. Craig Venter Institute. With key support from Ontario Genomics, the Symposium grew in the second year to over 200 participants from Western and other institutions, including McMaster, Waterloo and University of Toronto. A key objective of the Symposium was to provide a venue for undergraduate (including iGEM teams), graduate and postdoctoral trainees to present their synthetic biology research. This year, we are hoping to capitalize on momentum in grant successes to forge meaningful and productive collaborations with synthetic biologists from academic and biotechnology sectors, and we encourage all interested parties to attend. Our Twitter feed is https://twitter.com/Synbiosymp and the website is https://www.synbiowestern.com/. RSVP now – early registrations will be given priority for talks or posters (Early Bird period ends on June 26th). We hope to see you on July 26th!

Is Western University connected to other Canadian SynBio initiatives?
Yes, we are actively engaged with colleagues about upcoming synthetic biology initiatives. In particular, interest is growing in creating a Canadian component of the Genome Project – Write initiative, which aims to build on sequencing collected during Genome Project – Read to build synthetic chromosomes and organisms from the ground up. The first GP-Write Canada meeting is being organized by Vincent Martin (Concordia) and Bogumil Karas and will take place on August 13-14 in Montreal (https://www.gpwritecanada.com/).

Do you have any plans for further collaboration to strengthen these ties?
There are indeed opportunities to strengthen ties. We look forward to this through our upcoming Synthetic Biology Symposium and our sharing of research ideas with visitors and collaborators. We look forward to adding to speakers to the Western Synthetic Biology seminar series, and we are keen to assemble communities of researchers for future funding initiatives for synthetic biology research projects.

What is your vision for a successful SynBio community in 5 to 10 years?
We would like to see a seamless pathway for our students upon entering Western as undergraduates to gain academic and research training in leading edge Synthetic Biology science that will help them transition into their careers in SynBio-related areas. We envision close collaborative ties with industrial partners and other postsecondary programs in Canada, and hope that this IDI will lead to a greater synthetic biology presence in the biotechnology sector through spinoffs that develop as a result of training and research supported through the IDI. With the development of an undergraduate degree in Synthetic Biology and a Collaborative Synthetic Biology Graduate Program, we envision Western as the “go-to” destination for training and research in synthetic biology in Canada.

TCAG: The genomics powerhouse with a friendly face

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Founded in 1998 by Canadian genomics pioneers Drs. Lap-Chee Tsui and Stephen Scherer, The Centre for Applied Genomics (TCAG) provides world-leading infrastructure, technical expertise, and experimental and informatics support for innovative research in genomics. TCAG is located on a full floor of the Research Institute of The Hospital for Sick Children (SickKids), in the Peter Gilgan Centre for Research and Learning in downtown Toronto, and is affiliated with the McLaughlin Centre and the University of Toronto. The centre is a founding member of Canada’s Genomics Enterprise (CGEn), a national genomics platform that is one of the Major Science Initiatives funded by the Canada Foundation for Innovation (CFI) as a national platform critical to Canada’s research success. Its friendly staff of approximately 100 includes highly skilled bioinformatics, statistics, and laboratory personnel, core facility managers, embedded researchers, Associate Investigators, and an administrative team. The group works closely with client scientists to ensure success of their projects.

TCAG contains individual core facilities that collectively form a full-service, end-to-end genomics pipeline that can accommodate projects from the very small to the very large. These include cores in Informatics & Biostatistics, Sequencing, Microarrays & Genotyping, and Cytogenomics & Biobanking. The facilities are run by highly experienced managers (with an average of 8 years in the role), who consult with TCAG clients to ensure optimum experimental approaches. Data are generated on a fee-for-service, cost-recovery basis, and belong to the client. TCAG data handling and analysis activities take advantage of the SickKids High Performance Computing Facility (HPF) and HPC4Health Compute Canada node, both housed in our PGCRL building, as well as cloud-based resources. The centre also developed and hosts the Database of Genomic Variants (DGV). Last year, the DGV website was visited over 230,000 times by users from 88 different countries and is cited in over 350 publications every year.

Importantly, TCAG supports projects across a wide variety of disciplines: not only human biomedical research, but also in areas as diverse as agriculture and agri-food, fisheries and oceans, biopharma research, translational diagnostics, public health, bioinformatics, biostatistics, environmental sciences and biodiversity, and many other disciplines. Work for client projects is acknowledged in hundreds of publications per year, from the over 800 Principal Investigator scientists using TCAG’s services annually.

There have been many milestones in TCAG’s long history, some of which are highlighted below:

  • Since 2006, TCAG has provided services to over 2,200 laboratories: 85% from Canada including all ten Canadian Provinces; 45 countries; 331 academic institutions (universities, teaching hospitals and colleges); 157 companies (58% Canadian), and 49 government or NGO institutions. Dozens of trainees (students, fellows, visiting scientists, clinician-scientists, etc.) have trained within the facility.
  • TCAG is the first genome centre in Canada to install and operate Illumina HiSeq X whole genome sequencers; these are run alongside Illumina NovaSeq and other HiSeq instruments, and many other technologies including those for single-cell genomics (10X Genomics Chromium), single-molecule, long-read nanopore sequencing (PacBio Sequel), sensitive quantitative detection methodologies (digital droplet PCR, qPCR), and an extensive slate of targeted genotyping (Agena, Taqman, etc.) and genomic analysis resources.
  • TCAG developed the Ontario Population Genomics Platform repository that contains over 2,500 cell lines, DNA and demographic data from healthy controls, and has comprehensively genotyped over 850 of these. These data and population control DNA samples are available as a public resource.
  • Under the leadership of current Director Stephen Scherer, and in collaboration with Google, Verily, BioTeam and DNAstack, TCAG leads the Autism Speaks “MSSNG” project, generating whole genome sequences from 10,000 members of families with autistic children. Over 8,000 genomes have been completed to date, with analysis of the first 5,200 reported in Nature Neuroscience. The capacity and capabilities built for MSSNG have resulted in many benefits to TCAG clients. One recent example is the development of an improved pipeline for whole-genome copy number variation analysis.
  • TCAG has leveraged a total of over $223 million in funding over the past 20 years, including over $93 million in billed, cost-recovery services contributing to research studies in Canada and around the world. Major funding partners include CFI, the Ontario government’s Ministry of Research, Innovation and Science, Genome Canada, CIHR, the SickKids Foundation, and the McLaughlin Centre of the Unversity of Toronto.

Our group at The Centre for Applied Genomics will be pleased to help you with your research. Contacts for specific TCAG facilities can be found on our website. For general inquiries, please get in touch with TCAG’s Manager, Jo-Anne Herbrick, at (416) 813-8140, or jherbrick@sickkids.ca.