LSI investigators received nine new research grants totaling nearly $7.9 million in the latest Canadian Institutes of Health Research (CIHR) funding round, with an application success rate of 32.1% compared to the national average of 17.6%. The CIHR Project Grant program is highly competitive, and our investigators deserve kudos for their hard-earned success.
Richa Anand, Strategic Research Development Manager in the LSI, helped many LSI researchers prepare for this, and previous successes in CIHR and other competitions. The Research Services and Communications Core would be happy to assist in preparing new or revised applications for Spring 2020.
Below is a list of the investigators who received project grants this round and a summary of their research projects, which can also be found on the CIHR website.
Dr. Franck Duong was awarded $864,450 over 5 years for his project, entitled: “Development of a peptide-based membrane mimetic for solution studies in membrane protein research”.
Membrane proteins are a vital component of cells. Until recently, membrane proteins were not studied as extensively as cytosolic proteins. This is due to the propensity of membrane proteins to aggregate outside of a membrane environment during their isolation using detergents. Dr. Duong’s lab has developed a novel method of stabilizing membrane proteins — the “peptidisc” uses multiple copies of a unique peptide that wraps around membrane proteins, keeping them stable, soluble, and free of detergent effects. This technology will enable researchers to better study membrane proteins to understand their structure and activity, and how they interact with others proteins in the cell and with their environment.
Dr. Marc Horwitz was awarded $918,000 over 5 years for his project, entitled: “In vivo modeling of EBV’s role in the development of Multiple Sclerosis”.
Epstein-Barr virus (EBV) causes infectious mononucleosis (mono) and is believed to play a role in causing multiple sclerosis (MS). The goal of Dr. Horwitz’s research is to understand how the molecular and cellular changes that occur during latent EBV infection increase susceptibility and progression of MS, and specifically, elucidate the contribution of B cells, which are the target of latent EBV infection.
Dr. James Johnson had two successful applications. He was awarded $1,090,125 over 5 years for his project, entitled: “Mechanisms linking reduced circulating insulin to insulin sensitivity and longevity”.
High circulating insulin is a prominent feature of the worldwide epidemic in obesity and type 2 diabetes. Dr. Johnson’s group previously showed that a modest reduction in insulin secretion improves insulin sensitivity, a hallmark of metabolic health, and extends lifespan. For this project, they will conduct experiments to further understand the relationship between energy metabolism and aging, and determine how a small reduction in insulin can have such positive effects.
Dr. Johnson was awarded $1,090,125 over 5 years for a second project entitled: “Mechanisms by which hyperinsulinemia promotes pancreatic cancer”.
It has been suggested that excess insulin contributes to cancer initiation and/or progression, but this has never been tested directly in a way that can address cause and effect. The Johnson lab showed that a relatively modest reduction in insulin leads to a clear reduction in the early stages of pancreatic cancer. With this new project, they will determine how excess insulin promotes cancer, and whether the effects of insulin act directly on the cancer cells, or indirectly by altering something else in the body or the cells near the tumours. Their findings will have major implications for both cancer prevention via modification in nutrition or lifestyle, and for cancer treatment by inhibition of insulin signalling in tumours.
Dr. Hongshen Ma was awarded $524,026 over 3 years for his project, entitled: “Non-contact screening technology to expedite cell line development for antibody production”.
Antibodies are naturally produced by the body’s immune cells as defense against infection, and can also be used as a medicine to treat a wide range of diseases, including cancer, multiple sclerosis, and rheumatoid arthritis. A key barrier in developing antibody-based medicines is producing sufficient quantities for various stages of rigorous testing. Dr. Ma’s research will develop a technology to increase the productivity of cell lines used to produce antibodies, reduce the timelines required to develop antibody-based medicines, and thereby make the process more cost-effective.
Dr. Josef Penninger was awarded $868,275 over 5 years for his project, entitled: “Investigating the role of the BH4 pathway in Parkinson’s Disease (PD)”.
Parkinson’s disease (PD) affects 1 in 500 people in Canada. This devastasting neurodegenerative disorder results from the loss of cells in the brain that produce dopamine, a chemical that controls the body’s movements. The Penninger lab recently showed that tetrahydrobiopterin (BH4), a molecule that is essential for the functioning of enzymes that produce dopamine and other brain chemicals, has a second role in T cell activation by controlling mitochondrial bioenergetics. They hypothesize that BH4 controls mitochondrial processes in the nervous system, since mitochondria play a role in the deterioration of nerve cells in neurodegenerative diseases such as PD. In this project, the Penninger lab will test the role of BH4 in PD and whether increasing BH4 production can reduce the disease. They will further study the effects of BH4 in cells from patients to demonstrate the therapeutic potential of BH4 in PD.
Dr. Kenji Sugioka was awarded $745,875 over 5 years for his project, entitled: “Dissecting the flow-induced symmetry-breaking of animal cell division”.
Cytokinesis is a critical step in cell division that separates a dividing cell into two daughter cells. By controlling the position and orientation of division, cytokinesis can affect the arrangement of cells in space, which is important for the development of the animal. However, defects in cell division orientation are associated with cancer cells. The Sugioka lab studies the contribution of cortical flow, the cell surface flow of the motor protein myosin, and its role as a driving force in the spatial control of cytokinesis. They use state-of-the-art microscopy to study cortical flow in multiple modes of spatially controlled cytokinesis during the development of the model organism Caenorhabditis elegans. Their work is expected to expand the frontiers of cell division research, and due to the similarities between C. elegans and mammalian proteins involved in cell division, their findings will inform the study of human diseases such as cancer.
Dr. Guy Tanentzapf was awarded $921,825 over 5 years for his project, entitled: “The regulation of cell-matrix adhesion in mouse development and tissue homeostasis”.
The Tanentzapf lab will study how molecules called integrins are regulated in the body and how this regulation contributes to tissue formation and repair. Integrins are proteins found on the surface of cells that link cells to the extracellular matrix, a mixture of complex sugars and proteins that forms the base upon which tissues are built. Specifically, they will look at the contribution of integrins in (1) fibroblasts, which are specialized cells important in tissue repair, (2) melanocytes, which give skin its pigmentation, and (3) platelets, which are responsible for blood clotting. They aim to understand how integrins are controlled during human development and tissue maintenance, and also provide insight into how dysregulation of integrin function leads to disease.
Dr. Calvin Yip was awarded $856,800 over 5 years for his project, entitled: “Investigating the structure and function of the human autophagy regulatory EPG5”.
Autophagy is an essential “junk removal” system used by all cells in our bodies to package large objects such as cellular organelles and protein aggregates and deliver these packages to the “cellular incinerator”, the lysosome, for breakdown. Autophagy malfunction affects the normal balance between production and breakdown and has been shown to lead to a wide range of human diseases from neurodegeneration, cancer, to infectious diseases. Dr. Yip’s group aims to obtain a comprehensive understanding of how autophagy operates at the molecular level by studying the protein machinery that coordinates this multi-step process. They will focus on EPG5, a recently identified component of this machinery, and use sophisticated microscopy and crystallography techniques to obtain detailed structural information about this protein and figure out how EPG5 recognizes junk packages. In the long term, their research may lead to the development of targeted therapeutics for the treatment of human diseases where autophagy malfunction has occurred.