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Molecular Characterization of Autophagic Cell Death

Exploring the molecular mechanisms essential to autophagy and cell death with genetic, genomic, molecular and proteomic approaches using Drosophila and mammalian cell lines.

Project Leaders Sharon Gorski
Project Co-Investigators Gregg Morin
Involved Organizations
Genome Sciences Centre
Funding Agencies
Canadian Institues of Health Research

Overview

Autophagic cell death is a morphologically based term used to describe cell death that is associated with features of autophagy.  The molecular basis of the relationship of autophagy to cell death is not well understood.

The main objectives of this program are to identify and characterize genes that are required for apoptosis, autophagy, and/or autophagic cell death, and to investigate the relationships between these processes. Initial discovery and characterization of genes will be conducted using the model organism Drosophila. Further validation and characterization of select genes will be conducted in mammalian cell lines. Current avenues of investigation include the following:

  1. RNAi-based screen for Drosophila genes that affect steroid hormone-regulated cell survival and cell death.

  2. Identification of common regulators of apoptosis and autophagy. This study involves the development of an efficient flow cytometry and RNAi-based screening method for the identification of autophagy-related genes, and its subsequent application to known Drosophila cell death genes.
  3. Functional characterization and protein-protein interaction analysis of a Drosophila autophagic cell death related gene.  
  4. Screening and analysis of candidate regulators of autophagy in human cancer cell lines.

 

Recent Publications by our Research Team:

  • Chittaranjan S, McConechy M, Hou YC, Freeman JD, DeVorkin L and Gorski SM. Steroid hormone control of cell death and cell survival: molecular insights using RNAi. Plos Genetics. 2009, 5(2) e/000379.
  • Hannigan AM, Gorski SM. Macroautophagy: The key ingredient to a healthy diet? Autophagy. 2009 Feb 3;5(2): 140-51.Abstract
  • Hou YC, Hannigan AM, Gorski SM. An executioner caspase regulates autophagy. Autophagy. 2009, May;5(4):530-3.Abstract
  • Hou YC, Chittaranjan S, Gonzalez S, McCall K and Gorski SM. Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis. The Journal of Cell Biology. 2008, Sept. 22;182(6):1127-39.
  • Qadir M, Kwok B, Dragowska WH, To KH, Le D, Bally MB, and Gorski SM. Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Research and Treatment. 2008 Dec;112(3):389-403.Abstract
  • Klionsky DJ, Abeliovich H, Agostinis P, Agrawal D….....Gorski SM et al… Guidelines for Monitoring Autophagy in Higher Eukaryotes. Autophagy 2008 Feb;4(2): 151-175. (multi-author/institution review)
  • Copeland JM, Bosdet I, Guo M, Freeman JD, Guo M, Gorski SM* and Hay BA. Echninus, required for interommatidial cell sorting and cell death in the Drosophila pupal retina, encodes a protein with homology to ubiquitin-specific proteases. BMC Developmental Biology. 2007 Jul 5;7(1):82- . *Co-corresponding author
  • Akdemir F, Farkas R, Chen P, Juhasz G, Medvedova L, Sass M, Wang L, Wang X, Chittaranjan S, Gorski SM, Rodriguez A, Abrams JM. Autophagy occurs upstream of or parallel to the apoptosome during histolytic cell death. Development. 2006 Apr;133(8): 1457-1465.

 



Contact Information

For all project related inquires please contact us.

Stephanie McInnis, Project Coordinator
Genome Sciences Centre, BC Cancer Agency
Email: smcinnis@bcgsc.ca
Phone: 604-675-8000 x 7965
Fax: 604-675-8178