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Role of nuclear architecture in cancer development

Objective

Nuclear shape is one of the gold standards for detection and characterization of cancers. Nonetheless the control of nuclear morphology and its relationship to malignant behaviors are still poorly understood. We propose to study the mechanisms that lead to nuclear dysmorphia and their consequence on nuclear functions such as genome integrity and migration. The first part of the research will start from a list of actin regulators that, in preliminary experiments, showed role in controlling nuclear shape and/or DNA repair. An integrated combination of cutting edge biophysical and imaging techniques will be exploited to analyze in detail the biophysical features of nuclei and to address the potential role of the different pools of actin on nuclear shape and deformability. A relevant part of the project will be dedicated to characterize the molecular mechanisms downstream of the candidate genes and to test their role in the context of 3D migration and genome integrity.
Nuclear size and stiffness represent a significant obstacle to cell migration. However, cancer cells successfully shape their nuclei to efficiently migrate through gaps with otherwise limiting dimensions. In final part of our proposal we plan to perform a RNA interference screening to isolate genes that allows migration through limiting-size pores. The candidate hits will then be studied for their role in nuclear architecture and functions.
Our proposal supports the idea that the nuclear structure might be a bridge between different hallmarks of cancer and might uncover a new layer of the control of these aggressive traits in cancer.

Field of science

  • /natural sciences/chemical sciences/inorganic chemistry/inorganic compounds
  • /social sciences/sociology/social problems/migration
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /natural sciences/biological sciences/genetics and heredity/genome

Call for proposal

FP7-PEOPLE-2013-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
Address
1 Midland Road
NW1 1AT London
United Kingdom
Activity type
Research Organisations
EU contribution
€ 231 283,20
Administrative Contact
Heather Joanne Woods (Ms.)

Participants (1)

CANCER RESEARCH UK LBG

Participation ended

United Kingdom
Address
St John Street 407 Angel Building
EC1V 4AD London
Activity type
Research Organisations
Administrative Contact
Holly Elphinstone (Ms)