Microtubules of muscle cells (in green)

Microtubules of muscle cells (in green)

The laboratories of Amy Shaub Maddox and Paul Maddox at the Institute for Research in Immunology and Cancer (IRIC) of the Université de Montréal, in collaboration with David Sherwood at Duke University in North Carolina, published recently in Developmental Cell, a new approach to observe microtubules, a common anticancer drug target, in a novel context.

Led by Benjamin Lacroix, former postdoctoral fellow in Amy Maddox’s team, the publication presents a novel in situ system using the developing egg-laying apparatus of a small model organism, the nematode worm C. elegans. Dr. Lacroix used this system to image and measure all parameters of microtubule dynamics. This work highlighted some unexpected MT behaviours specific to proliferating versus differentiated cells that could help to develop more specific therapeutic agents. In addition, the study illustrates a new way of displaying these complex data sets. This system has been developed in collaboration with Jonas Dorn, a former postdoctoral fellow in Amy and Paul Maddox’s laboratories.

“Before joining Dr. Maddox’s laboratory in 2010, I didn’t know it was possible to look at a precise behaviour such as MT dynamics in an intact animal during its development. This entire project emerged when I realized the resolution we could reach using C. elegans nematodes and the high-power microscopes in our lab. I really enjoyed looking at a very well-studied aspect of cell biology from a totally new angle » said Benjamin Lacroix, presently a postdoctoral fellow at the Institut Jacques Monod in Paris.

“Dr. Lacroix benefited from the techniques and approaches developed in my laboratory in IRIC and also through the Institute’s bio-imaging core facility. I was amazed at his creativity and hard work all aimed at understanding how the dynamics of the microtubule cytoskeleton change as cells differentiate. Dr. Lacroix is dedicated to aiding the discovery of an ideal drug would only target cancer cells and have minimal effect on normal cells”, states Amy Maddox, principal investigator at IRIC from 2007 to 2013.

Context

Amy Maddox’s team is a multidisciplinary laboratory using a combination of cell biology, developmental biology and computer science. The group uses high-resolution light microscopy and the advantages of the free-living worm C. elegans, in which most cellular processes and proteins are similar to humans. The laboratory is particularly interested in bringing cell biological approaches to more complex and physiological settings to observe cytoskeletal behaviours that cannot be readily observed in classical in vitro studies.

Microtubules are dynamic cytoskeletal filaments present and essential in every eukaryotic cell. They are particularly important during cell division during which they build a structure called the mitotic spindle. Several drugs that target microtubules are used as cancer therapies because of their ability to block cell proliferation. These drugs, such as Taxol, are efficient against numerous cancers. However, patients treated with these drugs also develop devastating side effects due to the drugs’ effect on microtubules on non-cancer cells like neurons and muscle cells. In order to develop a truly cancer-specific drug, we need to better understand the differences between microtubules in proliferative and non-proliferative cells.

Cited study:

In situ imaging in C. elegans reveals developmental regulation of microtubule dynamics.
Lacroix B, Bourdages KG, Dorn JF, Ihara S, Sherwood DR, Maddox PS, Maddox AS
Dev. Cell 2014;29(2):203-16.

About the Institute for Research in Immunology and Cancer

An ultra-modern research hub and training centre located in the heart of the Université de Montreal, the Institute for Research in Immunology and Cancer (IRIC) was created in 2003 to shed light on the mechanisms of cancer and discover new, more effective therapies to counter this disease. IRIC operates according to a model that is unique in Canada. Its innovative approach to research has already led to discoveries that will, over the coming years, have a significant impact on the fight against cancer. For more information: www.iric.ca