David W. Andrews

Biography

Our research areas include cancer chemotherapy, the molecular mechanisms by which Bcl-2 family proteins regulate apoptosis, the assembly of proteins into the cellular membranes, high-content screening, the development of new fluorescence microscopes and automated image analysis techniques. We are studying the mechanisms by which the Bcl-2 family of proteins regulate selective programmed cell death (apoptosis) of cancer cells. We are particularly interested in determining how cells respond to chemotherapy drugs. The Bcl-2 family proteins that we study include those that initiate cell execution (Bax and Bak), as well as those that inhibit (Bcl-2, Bcl-XL, Mcl-1) or promote (Bim, Bid, Bad) the process. Our recent data indicate an unexpected role for binding to membranes in regulating how Bcl-2 family proteins interact with each other. We believe that by studying protein to protein interactions where they take place-in the membranes of live cells-we will be able to identify more effective therapies. Examining protein to protein interaction is one of the most challenging areas of cell biology. To extend our analyses to live cells and to include measurements of the effects of drugs and drug candidates we have developed new approaches, instruments and software. With industrial partners we are developing new automated microscopes that provide both time and chromatic spectral data that we use to measure protein to protein interactions and to perform drug mechanism studies. These instruments generate data sets containing millions of images. In order to analyse these images we have written new machine learning software for image analysis and cell classification. Our current imaging techniques include automated fluorescence microscopy, fluorescence lifetime imaging, fluorescence correlation spectroscopy, single molecule imaging and hyperspectral imaging. Our imaging research recently culminated in the establishment of a new $9-million image-based screening facility at Sunnybrook Research Institute.

Research Interest

Molecular membrane biology,Cancer research,High-content screening,Automated image analysis,Apoptosis