Cells in the human body continuously change behaviour in response to physical and chemical cues from the extracellular environment. For example, immune cells migrating towards lymph nodes encounter environments with heterogeneous physical properties. They respond to these different mechanical stimuli by changing activity, migratory behaviour, and interior organization. Similarly, cancer cells undergo profound modifications as they invade tissues, and changes in the physical properties of the tumour microenvironment can modify their migratory ability. In both examples, the cellular responses arguably also involve changes in gene transcription and the underlying mechanisms remain unresolved yet.
Mechanical forces as compression, shear, tensile stress, and hydrostatic pressure are some of the main microenvironmental physical signals to which cells in the human body are continuously exposed. These mechanical forces have fundamental effects on cell behavior through reprogramming of gene transcription. However, how mechanical signals induce epigenetic changes on chromatin with consequent activation or inactivation of specific transcription factors is poorly understood.
Project
The aim of this project is to identify molecular mechanisms regula?ting gene expression induced by nuclear deformation. It will be studied how such physical sig?nals are transduced to the nucleus and induce epigenetics reprogramming on histone tails to modulate gene expression.
In this project, the master student will learn cellular and molecular biology techniques to identify alterations in molecular complexes induced by cell confinement. In more detail, the response of human fibroblasts to compression will be compared to non-confined cells, and potential molecular mechanisms will be identified using the following methods:
Methods
This project will use techniques in biochemistry, cellular and molecular biology, including:
- recombinant DNA technology
- protein expression and purification
- immunoprecipitation
- Western blotting
- cell culture
- cell transfection
- RNA interference
- immunofluorescence and state-of-the-art microscopy techniques, and use of different microscopes available at the NorMic imaging platform
- quantitative image analysis using software such as ImageJ, Imaris, etc.
Workplace and environment
The project will be performed at the Department of Biosciences in the groups of Cinzia Progida and Jonas Paulsen. The groups consist of researchers at different stages of their careers (Master, PhD students, post-docs, and an experienced technician).