Research group of Professor Streuli, University of Manchester

Research group of Professor Streuli, University of Manchester

The Streuli lab, from left to right: Nikki Paul, Julia Cheung, Lisa Brackenbury, Fiona Foster, Charles H Streuli, Melanie Ward, Pengbo Wang, Apolinar Maya-Mendoza, Weiping Li and Nasreen Akhtar

Professor Charles Streuli leads a research group within the Faculty of Life Sciences at the University of Manchester, UK. Charles’s group was established in 1992 to elucidate the molecular basis of how integrin-mediated adhesion regulates epithelial cell fate. Charles was appointed Professor of Cell Biology in the University’s Faculty of Life Sciences in 2002. In 2007, he co-founded and became Research Director of the Breakthrough Breast Cancer Research Unit at the University of Manchester. He is currently the Director of the Wellcome Trust Centre for Cell-Matrix Research. 

A major focus of the research in Charles’s lab is to elucidate the mechanisms by which integrins and their signalling proteins regulate the development and function of the mammary gland. This tissue is organised into a branching network of hollow tubes (ducts) with alveolar (acini) structures similar to many other internal organs such as the lungs, pancreas and kidney. Researchers are particularly interested in how signals from the extracellular matrix (ECM) are involved in cellular differentiation and in establishing polarity within multicellular tissues, which leads to the assembly of ducts and acini containing hollow lumens. Moreover they are interested in how these signals become subverted during breast cancer initiation.

The Streuli lab has developed sophisticated techniques to examine mammary gland architecture in vivo, as well as 3-dimensional cell culture models that allow acinar morphogenesis and expression of tissue-specific gene products. 

Recent gene ablation studies in mice, using the Cre-LoxP approach have revealed that downstream of the ECM, ß1-integrins are critical for the morphogenesis of the mammary gland and development of acini with a single central lumen. ß1-integrin null acini lack a central cavity and display a similar dysmorphology to ductal carcinoma in situ, an early form of breast cancer (see movies 1 and 2).

Nasreen Akhtar is a postdoctoral researcher in the Streuli lab. Nasreen obtained a PhD at the University of Birmingham, studying the role of the EGF receptor in human breast cancers. She joined Charles’s lab in 2001 and is currently investigating how integrins and Rho GTPases regulate polarity and differentiation in mammary epithelia.

Nasreen says “We have used Volocity for a number of years to deconvolve image stacks of the 3D acinar structures and to merge colored images. Recently, the 3D rendering function has enabled us to re-build both the in vivo mammary gland tissue and cultured acini, allowing us to view the morphogenesis defects in our knockout tissue from several angles”.

Movie 1 shows a 3D reconstruction of a polarized mammary epithelial acinus with a hollow lumen in the middle (green; ß1-integrin and red; atypical PKC: primary cells were isolated from mouse mammary glands and cultured on a reconstituted BM-matrix). A third of the stack has been removed to display the luminal cavity in the centre. Movie 2 shows an acinus where the ECM receptor, ß1-integrin has been deleted: note the disorganized polarity and the lack of a central cavity.

Find out more about the Streuli lab