Structural Genomics Consortium

The Structural Genomics Consortium (SGC)  is an international public-private partnership incorporated as a not-for-profit organization in July 2004 that supports the discovery of new medicines through open-access research. Its core mandate is to determine the 3D structures targeting human proteins of biomedical importance and proteins from human parasites that represent potential drug targets. To date the SGC has been responsible for more than 25% of global output of new human protein structures and more than 50% of the global output of protein structures from human parasites.

The SGC is led by Aled Edwards at the University of Toronto with additional activities at Oxford University. Each site is led by a Scientific Director reporting to Edwards. The SGC began in 2003 and the first two phases of the project has delivered over and above its initial goals. Phase III of the SGC began July 1, 2011. A total of $61 million has been committed by funding partners, of which $28 million is from the public sector (including $2.5 million for one year from Genome Canada) and $33 million from the private sector, including GSK, Pfizer, Novartis, Lilly, Life Technologies, Abbott Laboratories and Takeda Pharmaceuticals, with at least two new companies requesting membership. In addition, SGC has secured at least $8M of in-kind support from pharmaceutical companies. http://www.thesgc.com/

On October 26, 2020,  on behalf of Minister of Innovation, Science and Industry Navdeep Bains, William Amos, Parliamentary Secretary (Science), announced $16 million in federal support to 10 new genomics research projects funded through Genome Canada. Provincial governments, businesses and research partners are also investing nearly $41 million in co-funding, for a total investment of almost $57 million in the areas of health, agriculture and the environment.

On June 12, 2017, the Honourable Kirsty Duncan, Minister of Science, announced a new $33 million investment to support the Structural Genomics Consortium (SGC) – a Canadian-led, international public-private partnership that conducts basic science on the structures of human proteins and releases the research to the public to accelerate drug discovery and help patients worldwide. This latest investment in the fourth phase of Canadian-based SGC activities, conducted principally at the University of Toronto, includes $11 million in federal funding through Genome Canada, $5 million through the Government of Ontario, and an additional $17 million through pharmaceutical companies. This funding will help translate scientific discoveries into cures for patients with a range of diseases such as cancer, ALS, Huntington’s disease, malaria and tuberculosis.

Quick Facts

  1. The SGC is considered a pioneer in open science. Since its inception in 2004, the SGC has shared all research results and output with no restrictions on use, and without filing patents as a core principle. This approach protects against waste and duplication of effort, and catalyzes innovation by facilitating scientific exchange that is unencumbered by intellectual property considerations.
  2. Led out of Toronto, the SGC includes sister sites worldwide, engaging an ever-broadening number of public and private sector partners that collaborate to improve the lives of patients worldwide.
  3. To date, eight pharmaceutical companies are collaborating in and co-financing SGC activities. Outcomes to date include more than 25 ongoing clinical trials and the creation of many start-up companies

Structural Genomics Consortium, Phase IV

Overview

On June 12, 2017, the Honourable Kirsty Duncan, Minister of Science, announced a new $33 million investment to support the Structural Genomics Consortium (SGC) – a Canadian-led, international public-private partnership that conducts basic science on the structures of human proteins and releases the research to the public to accelerate drug discovery and help patients worldwide. This latest investment in the fourth phase of Canadian-based SGC activities, conducted principally at the University of Toronto, includes $11 million in federal funding through Genome Canada, $5 million through the Government of Ontario, and an additional $17 million through pharmaceutical companies. This funding will help translate scientific discoveries into cures for patients with a range of diseases such as cancer, ALS, Huntington’s disease, malaria and tuberculosis.

The estimated 100,000 different human proteins constitute the key functional and structural components of our and indeed all species; they are critical to normal development and health. Each protein, which is actually a long linear chain of amino acids, is folded into an exact three dimensional shape. This, the so called protein structure, is essential data when thinking about creating molecules such as drugs that bind and modify protein function.

Since 2004, the Structural Genomics Consortium (SGC) has been working to determine the three-dimensional structure of proteins relevant to human diseases. These structures are made available online in the public domain, without restrictions on their use by industry or academia, to support early-stage drug discovery.

To date, and with ongoing support from Genome Canada and other partners, the SGC is responsible for internationally leading 13 per cent of all solved human protein structures. The SGC also leads an international program in partnership with other scientists, research agencies and pharmaceutical companies, that generates small inhibitor molecules, called chemical probes, against proteins and makes them available in the public domain. The chemical probes help researchers understand the role of a protein in normal and disease physiology and play an essential role in the early drug-discovery process.

A key area of focus for the SGC is proteins that regulate epigenetics, the study of heritable modifications to gene expression. Understanding how proteins turn specific genes on and off is important for developing therapies to treat many debilitating diseases, such as cancer and neurodegenerative and inflammatory diseases. Based on SGC science, there are now more than 25 clinical trials ongoing, including in Canada.

Another example is when, because of genetic mutations, proteins are misinformed, resulting in one of the estimated 7000 different rare diseases which affect approximately one million 2 Canadians. Here, SGC’s ability to define protein structure can make all the difference. Care 4 Rare, a Genome Canada-funded large-scale applied research project, working with the SGC has identified the structure of a protein which may hold the key to therapy for a rare seizure disorder as well as discovering small molecules which bind to this protein, potentially serving as drugs; more recently the world’s first genetic model of the condition has been created and is now poised to perform pre-clinical testing of the SGC-enabled theory.

The SGC is considered a leader in open science. By sharing all research results and output with no restrictions on use, SGC’s open science ethos protects against waste and duplication of effort, and strengthens collaboration and innovation by facilitating scientific exchange that is unencumbered by intellectual property considerations.

In its current phase, the SGC is expanding its open science collaborative network to include disease and patient foundations. The SGC is also partnering with clinicians and research hospitals to test its chemical probes on patient samples, a more predictive approach to validating new targets for drug discovery. The project will also provide training for the next generation of Canadian researchers in early-stage drug discovery.

The Canadian arm of the SGC is co-supported by eight pharmaceutical companies and the Ontario Ministry of Research, Innovation and Science (MRIS). SGC has also established a robust collaborative research and training network among Canadian institutions with support from hospital research institutes, the Bill and Melinda Gates Foundation, the Natural Sciences and Engineering Research Council (NSERC), Canadian Institutes of Health Research (CIHR) and the Mitacs program.

The wider research program includes sister SGC sites at Oxford University (UK), the University of Campinas (Brazil), the Karolinska Institute (Sweden), the University of North Carolina (USA) and Goethe University Frankfurt (Germany).

Target 2035: WDR Proteins as a Technology Testbed for Illuminating the Dark Proteome

Overview

The Structural Genomics Consortium (SGC) will create a roadmap for Target 2035 – a global initiative that will dramatically increase the translation of genomics into new medicines. This two-year project is part of SGC’s Phase V, which runs from 2020 to 2025. The initial focus is on WD40 Repeat (WDR) domain proteins, one of the largest and most disease-associated protein families in the human proteome. In collaboration with industry, the team will focus on technology optimization, and position Canada as the global leader for Target 2035.

What exactly is Target 2035? The sequencing of the human genome raised great hopes that a new era of genomic therapies would soon follow. Most biomedical research has since focused on only a small fraction of genes and proteins for which accessible research tools exist, resulting in a vast knowledge gap limiting our ability to develop new medicines for debilitating diseases like Alzheimer’s, cancer, and rare diseases. Target 2035 is an ambitious new initiative to address this gap by developing a pharmacological tool for most human proteins by the year 2035, focusing on proteins considered part of the unexplored “dark proteome”. This tremendous task will transform drug discovery but can only be achieved through a coordinated international effort. In partnership with the pharmaceutical industry, the SGC lab at the University of Toronto (SGC-Toronto) is building and leading a Target 2035 global federation of scientists to take on this challenge.

Over the course of Phase V, the team will build directly on the previous success and momentum of the SGC-Toronto, using the platform to create community-enabling pharmacological tools at an unprecedented scale. In the first two years, the project will explore a range of innovative strategies including the application of artificial intelligence (AI), with a focus on WDR proteins, to test and compare technologies for protein production, screening of chemical libraries, and optimization approaches to identify small chemical molecules that bind and/or modulate WDR domains.

The WDR protein family is largely unexplored yet harbours more ‘essential genes’ in cancer than any other protein family, is involved in many other debilitating and rare diseases, and is amenable to pharmacological inhibition. Thus, it is an ideal ‘test set’ to develop protein-based, scalable technologies, workflows and collaborative models.

The two-year pilot phase (2020-2022) will:

  • Create drug discovery enabling reagents and know-how for 15–20 WDR proteins that are part of the “dark proteome”;
  • Generate 10 highly specific open access chemical compounds or ‘probes’ to disease-relevant WDR proteins that will catalyze the launch of new drug discovery programs; and
  • Establish a knowledge translation platform in collaboration with the European EUbOPEN project to manage, integrate and disseminate open-science chemical biology data, reagents and knowledge.

This pilot is an inclusive, pan-Canadian project designed to yield significant benefits. In the near term, this includes training and capacity building, new open data to catalyze AI-driven drug discovery, knowledge and technologies to empower national and global teams, while attracting public and private support. Over the longer term, this includes stronger innovation networks in Canada, inward investment for pre-clinical and clinical trial activities, and new medicines that will have a profound impact on Canadians’ quality of life. SGC aims to replicate their success with WDR5, for which SGC and the Ontario Institute for Cancer Research (OICR) created a chemical probe, which led to a $40 million investment in Propellon Therapeutic’s leukemia drug discovery program.

Critically, Target 2035 delivers on Genome Canada’s Strategic Vision to drive high-impact research to benefit Canada. The plan addresses key societal challenges associated with the enormously complex task of developing new drugs. The team will coordinate with other global groups to lead this large-scale, interdisciplinary initiative with line-of-sight to application. The resulting reagents and know-how will lead to new medicines in Canada through translational partnerships with research institutes across the country, five Canadian biotechs and 10 global Pharma companies, and a new cohort of open science spin-offs. Target 2035 is arguably the most ambitious genome effort since the Human Genome Project and will significantly advance Canada’s role in international genomics research, with SGC at the helm.