PLOIDYNET · The impact of chromosomal instability on health: Molecular causes and consequences of aneuploidy

Aneuploidy, an abnormal number of chromosomes, is a hallmark of cancer cells, affecting the majority of all human tumours. Aneuploidy arises when errors occur during mitosis, as the duplicated chromosomes are distributed between the two new daughter cells. Paradoxically, aneuploidy appears to have detrimental consequences for the physiology of untransformed cells in vitro, inhibiting rather than stimulating proliferation. This suggests that cancer cells have acquired mutations that help them cope with aneuploidy. Although it is clear that aneuploidy can contribute to cancer, the molecular consequences of aneuploidy remain elusive, as does how aneuploidy contributes to malignant transformation. The scientific aim of this network is to determine and compare the molecular consequences of different levels of aneuploidy, both in vivo and in vitro. Our network will train 9 Early Stage Career and 2 Experienced researchers in the aneuploidy field. To this aim, we are combining the expertise of labs that study the causes of aneuploidy with labs that induce aneuploidy in model organisms and study its consequences and also with labs that focus on the development of therapeutics that selectively kill aneuploid cell progeny. Our network is comprised of 11 full participants in 4 member states and 1 associated country and one associated partner, and includes 3 commercial enterprises. Within this network, we will provide technical training through research projects, but also through workshops and dedicated courses organized by the participants of this network. A significant part of the training will be provided by the industrial partners. Participating investigators and trainees will meet at a yearly conference to exchange and discuss results. Trainees will thus become experts in the field of aneuploidy while rapidly building up a scientific network for themselves, putting them in an excellent position to become future leaders in this field.