Biochemistry faculty awarded CIHR grants

Three Biochemistry faculty were awarded CIHR Project Grants as the Principal Investigators in the spring 2019 competition. Congratulations to them and their co-investigators: 

Dr. Murray Junop (Molecular Mechanisms of Non-homologous DNA End-joining)
Dr. Junop will receive $845,326 in research funding over the next 5 years to study the underlying mechanism of a form of DNA repair called non-homologous DNA end-joining (NHEJ). In this process, specialized proteins recognize double-stranded breaks in DNA and repair the damage by re-joining the DNA ends. This important step preserves genome integrity and avoids cancer.

The Junop research team will use the power of X-ray crystallography to examine the proteins involved in NHEJ at the molecular level. By doing so, insight will be gained into normal DNA repair involving NHEJ, which in turn will shed light on how this process functions abnormally to effect cancer. Such information will inform the development of cancer therapeutics.

This Project Grant will positively impact Dr. Junop’s research. He said, “Receiving CIHR funding is a tremendous asset for the lab. It will enable continuing and expanded aspects of our research, directed toward understanding the mechanisms of mammalian DNA repair, to move forward and also permit leveraging of gained information for translational applications.” 

Dr. Patrick O'Donoghue (Pathways to Neurodegeneration from Natural Human tRNA Variation)
Dr. O’Donoghue and his co-investigators [Drs. Chris Brandl (Biochemistry), Martin Duennwald (Pathology and Laboratory Medicine), and Amanda Moehring (Biology)] have been awarded $865,980 over the next 5 years to study the relationship between human tRNA variants and their contribution to neurodegeneration. Protein synthesis depends on many cellular components working together to ensure the accuracy of the amino acid sequence, which in turn controls subsequent protein folding. Major players in protein synthesis include tRNAs, which read the mRNA code and carry the corresponding amino acid to the growing polypeptide chain. Any errors by tRNAs can result in errors in protein synthesis, followed by protein misfolding and aggregation, all with potential for disease.

The O’Donoghue team will determine if certain human tRNA mutations cause mistranslation and misfolding of proteins associated with neurodegenerative disease. Their project holds promise to identify genetic mutations that cause mistranslation as an important contributor to neurodegeneration. Their data will also be relevant to other age-related diseases characterized by compromised protein quality in cells, such as cancer and cardiovascular diseases. 

Dr. Gary Shaw (Mechanisms of Ubiquitination in Neurodegeneration)
Dr. Shaw and his co-investigator, Dr. Martin Duennwald (Pathology and Laboratory Medicine), will receive $1,123,594 in research funding over the next 5 years to examine the structure and function of parkin, a protein that is defective in Parkinson’s disease. Parkin is an E3 ubiquitin ligase, which adds ubiquitin to proteins destined for degradation. Such a process ensures the removal of damaged and excess proteins from cells. Parkin also limits oxidative damage to mitochondria, which produce energy for motor control, especially in the brain.

Using NMR, Dr. Shaw and his research team will examine the three-dimensional structures and functions of parkin with and without its disease-causing substitutions to understand how resultant changes cause dysfunction in ubiquitination. Such research will provide a foundation for the future development of therapeutics for Parkinson's disease.