The award highlights, once again, the necessity and the enormous impact of Basic Research in our understanding of fundamental principles of life, and in the development of innovative therapies for major diseases. Only 40 years have passed since the original molecular characterization of Notch in the fruitfly, by Dr. Artavanis-Tsakonas in 1985, and in the nematode worm, by Dr. Iva Greenwald in 1989.

Today, major biotechnology companies are developing Notch-targeted therapeutics for many human diseases. It is worth mentioning that one of the two international meetings of the now populous Notch scientific community is held biannually in Athens and sponsored by the Fondation Santé, a non-profit organization that also supports Greek researchers; in alternate years the American Notch meeting is part of the prestigious Gordon Conference series.

Excerpts from the Foundation’s description:

Drs. Spyros Artavanis-Tsakonas, Iva Greenwald and Gary Struhl are awarded for establishing our foundational understanding of Notch signaling, defining how this pathway works at the molecular level and how it influences cell fate, development, and tissue patterning.

Notch was first identified over 100 years ago as a mutation that causes notches in the wings of fruit flies (Drosophila). Over time, it became clear that Notch defines an evolutionarily conserved gene network involved in diverse aspects of development in many different species, including mammals. Pioneering genetic and molecular work by Dr. Artavanis-Tsakonas led to the cloning of the Drosophila Notch gene and other components of the pathway. Notch turned out to be a membrane-bound receptor defining the central element of a cell signalling pathway that interacts with another membrane-bound molecule on adjacent cells, leading to intracellular signaling and changes in cell fate.

Dr. Greenwald discovered and cloned the Notch gene LIN-12 in nematodes (C. elegans), elucidated its fundamental role in cell fate specification, and identified many core components of the pathway, including the intramembrane protease Presenilin implicated in Alzheimer's Disease. Drs. Greenwald and Struhl together proposed that Notch functions as a membrane-tethered transcription factor that is cleaved to release the cytosolic domain, which enters the nucleus to control gene expression. Dr. Struhl then pioneered the use of chimeric proteins to validate the cleavage model and demonstrate that Notch is activated in response to mechanical force exerted by ligands.

Drs. Artavanis-Tsakonas, Greenwald and Struhl’s findings have had far-reaching implications for both basic science and medicine, particularly in identifying the role of Notch signaling in diseases such as cancer and developmental disorders, and shared components with neurodegenerative diseases like Alzheimer's.

More info: https://www.gairdner.org/resource-hub/2025-canada-gairdner-award-winners