Lymphocyte defects in X-linked lymphoproliferative disease

Dr. Ala Aoukaty has spent nine years investigating anti-viral and anti-tumour cells. Aoukaty’s doctoral research focused on understanding the signalling process that occurs after receptors on the surface of cells are engaged. That experience provided him with a strong background to conduct postdoctoral research on X-linked lymphoproliferative disease (XLP), a fatal disorder caused by a genetic mutation and characterized by severe infectious mononucleosis, immune deficiency and malignant lymphomas (tumours). A large Aboriginal family that carries the genetic mutation has been identified. Aoukaty will isolate and study cells from XLP patients and carriers of the disease in the family to study the abnormal immune responses at work. The research will shed light on how the immune system specifically responds to Epstein-Barr virus, which causes infectious mononucleosis, provide insights in general about lymphoproliferative disorders (diseases of immune system tissue), and enable the testing of gene replacement therapies.

Utilization of large-scale genomic yeast modifier screens in the identification of unique genes required for chromosome segregation

Chromosome segregation is a fundamentally important process for human cells. When cells divide, they normally ensure both daughter cells receive one copy of each chromosome. But defects in this process can cause cells to lose chromosomes or receive extra ones. Inaccurate chromosome segregation can lead to diseases such as cancer. Despite the importance of this process, researchers are just beginning to identify and understand the genes and molecular mechanisms involved. Dr. Kristin Baetz is investigating the genes and mechanisms needed to ensure accurate chromosome segregation. Baetz is developing a genomic screen to identify unique genes in a genetic yeast model, whose genome and cell biology are remarkably similar to that of humans. Building knowledge about chromosome instability could lead to new treatments for common forms of cancer.

Analysis of altered gene expression in YAC transgenic mouse models for Huntington disease

Research has confirmed that an inherited mutation in the huntingtin protein causes Huntington disease, a progressive and ultimately fatal neurological disorder that usually starts in mid-life. There is much more to be learned about the onset and course of the disease and there is no effective treatment. Dr. Edmond Chan is addressing those gaps by profiling gene expression in mice with Huntington disease. His research aims to identify altered patterns of gene expression that link with early, mid and late stages of the disease. The profile may identify genes involved in initiating the process that leads to progressive damage and death of brain cells. Chan will formulate and test specific theories that connect gene expression patterns with the molecular development of Huntington disease. Ultimately, genes identified in the research could suggest treatment strategies to improve quality of life for patients with the disorder.

Gene Therapy for a genetic cardiovascular disease: AAV-mediated gene transfer of a powerful, naturally occurring, LPL-S447X variant for the treatment of LPL deficiency

Dr. Colin Ross believes that studying genetics and diseases at the molecular level can open many doors for the treatment of diseases at their root causes. He’s doing exactly that in cutting edge research to develop treatments for a genetic cardiovascular disease that has the highest worldwide frequency in Canada’s French-Canadian population. People with lipoprotein lipase (LPL) deficiency are missing a key enzyme that helps break down triglycerides (fats) in the blood stream. Elevated levels of these fats can cause serious, life-threatening damage to the pancreas, heart and other organs. Ross is working on the development of gene therapy techniques to implant healthy genes into cells to restore production of the missing enzyme. He ultimately aims to develop a safe and long-term treatment for LPL deficiency.

Characterization of the Ctf3/Mcm22/Mcm16 outer kinetochore complex; a link to the yeast spindle pole body

In order for cells to grow properly, chromosomes must accurately separate to opposite poles of the dividing cell. Mistakes in this process can lead to cancer due to instability of the chromosomes. Dr. Vivien Measday is using a yeast model to study chromosome segregation. She has a particular interest in the centromere, the region of the chromosome required for proper segregation, and the kinetochore, which consists of centromere DNA and its associated proteins. Using genetic screens, Measday is identifying and characterizing kinetochore proteins. Studying these proteins will increase understanding of why chromosomal instability occurs in cancer cells and in other disorders such as Down’s syndrome.