Cell adhesion, mechanotransduction and breast biology

Adhesion provides a way for cells of multicellular organisms to sense their location and respond to the environment. One of the most exciting recent advances in cell and molecular biology is the realisation that physical cues from the cellular microenvironment profoundly affect cell behaviour. Thus, the elasticity of the microenvironment, and the intracellular tension that this generates, can determine gene expression. The conversion of physical cues into intracellular signals is called mechanotransduction.

My lab determines how cellular adhesion regulates breast epithelial cell proliferation and differentiation, and stem cell function. We have previously shown that cell interactions with the extracellular matrix have a profound effect of tissue-specific gene expression in this tissue. Recently we discovered that the elasticity of the local microenvironment also determines gene expression in breast cells. Current research is focussed on understanding how mechanotransduction controls the transcription of a key gene required for breast differentiation, namely prolactin-receptor.

This project provides an exciting opportunity to explore how intracellular tension controls the transcription of tissue-specific genes in epithelia. Using lentiviruses that express inducible shRNAs, you will transduce epithelial cells with candidate effector proteins, to identify the possible signalling pathways that are involved. You will also develop new ways of manipulating the forces imposed on cells and methods of measuring the forces generated within individual cells.

The overall vision of this project is to resolve how mechanotransduction contributes to gene expression, thereby tackling an unanswered question in cell biology.