Genes to affordable medicines - Stream 1-B1

The Structural Genomics Consortium (SGC) is a not-for-profit public-private partnership research organization that aims to accelerate the discovery of new medicines through open science. This Mitacs cluster will bring together SGC’s industry and academic collaborators to work together towards new and affordable medicines for challenging diseases. Sixty-three post-doctoral fellows will spend 2-3 years developing open source tools and knowledge for previously understudied proteins, thereby unlocking new areas of biology and identifying new opportunities for drug discovery.

Targeting the ubiquitin system function through GID4 - Year two

Protein turnover is an incompletely understood aspect of biology, important for various processes including adaption to environmental stimuli. Over 500 protein complexes (E3 ligases) are involved in marking proteins for degradation, but only a small number of these E3 ligases are well characterised. The current project seeks to develop chemical inhibitors of GID4—a key component of an E3 ligase complex called C-terminal to LisH (CTLH). This E3 ligase is thought to play a role in nutrient sensing and autophagy, which are both implicated in chemotherapy resistance of cancer cells.

Investigating WD repeat protein function in the nucleolar biology and cancer

Ribosome biosynthesis is one of the most multifaceted and energy-demanding processes in biology. It involves over 250 factors that transiently associate with the nascent pre-ribosome in a well-orchestrated manner. Importantly, increased ribosome biogenesis has a critical role in cancer initiation and progression. Owing to the advances in cryo-electron microscopy, this pathway's detailed mechanism started to be revealed, setting the grounds for new therapeutic interventions. The current project seeks to develop chemical probes for WD repeat proteins, a new drug target class.

Genes to affordable medicines - Stream 1-A1

The Structural Genomics Consortium (SGC) is a not-for-profit public-private partnership research organization that aims to accelerate the discovery of new medicines through open science. This Mitacs cluster will bring together SGC’s industry and academic collaborators to work together towards new and affordable medicines for challenging diseases. Sixty-three post-doctoral fellows will spend 2-3 years developing open source tools and knowledge for previously understudied proteins, thereby unlocking new areas of biology and identifying new opportunities for drug discovery.

Genes to affordable medicines - Stream 1-A2

The Structural Genomics Consortium (SGC) is a not-for-profit public-private partnership research organization that aims to accelerate the discovery of new medicines through open science. This Mitacs cluster will bring together SGC’s industry and academic collaborators to work together towards new and affordable medicines for challenging diseases. Sixty-three post-doctoral fellows will spend 2-3 years developing open source tools and knowledge for previously understudied proteins, thereby unlocking new areas of biology and identifying new opportunities for drug discovery.

Targeting SARS-CoV-2 (COVID-19) methyltransferases (nsp14 and nsp10-nsp16 complex) toward developing small molecule antiviral therapeutics - Part 2

COVID-19 pandemic has brought the world to standstill with more than 55 million people infected to-date and more than 1.34 million mortality so far. It has literally brought the health care systems in many countries to the breaking point, if not beyond. The economic consequences have been devastating with millions of people out of work. We are taking a novel approach by focusing on two SARS-CoV2 (COVID-19) methyltransferases that are essential for viral replication. Both enzymes (nsp14 and nsp16) are druggable.

Genes to affordable medicines - Stream 2-L

The Structural Genomics Consortium (SGC) is a not-for-profit public-private partnership research organization that aims to accelerate the discovery of new medicines through open science. This Mitacs cluster will bring together SGC’s industry and academic collaborators to work together towards new and affordable medicines for challenging diseases. Sixty-three post-doctoral fellows will spend 2-3 years developing open source tools and knowledge for previously understudied proteins, thereby unlocking new areas of biology and identifying new opportunities for drug discovery.

Defining epigenetic drivers of primary and metastatic medulloblastoma - Year two

Medulloblastoma (MB) is the most common childhood brain cancer. Current treatment for these tumors is invasive involving irradiation of the entire brain and spine. Although some types of MB respond well, others have an abysmal prognosis, and the lack of less invasive therapies means that children undergoing treatment suffer from severe developmental defects and reduced quality of life.

Epigenetic Regulators of Anticancer Drug Response

The effectiveness of cancer drugs depends on several factors which are governed by the genetic and ‘epigenetic’ code of cancer cells. The epigenetic code comprises those heritable modifications that bookmark DNA and DNA-associated proteins to guide the expression of genetic attributes without changing the DNA sequence. This epigenetic code is written, read, and erased by a group of proteins known as epigenetic regulators.

Structural characterization and mechanism-based inhibition of TMPRSS2, a human protease that activates SARS-CoV-2

The novel SARS-Coronavirus-2 becomes activated and is infective after interacting with the human TMPRSS2 enzyme, as it primes the virus to enter and hijack lung cells for viral replication. By designing drugs using a strategy that has shown success in inhibiting enzymes structurally similar to TMPRSS2 and understanding the exact shape of this enzyme in greater detail, highly specific drugs can be engineered to block SARS-CoV-2 activation and alleviate symptoms contributing to COVID-19 mortality.

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