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LMCB - MRC Laboratory for Molecular Cell Biology

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Franck Pichaud's picture
LMCB Group Leader, UCL Professor of Cell and Developmental Biology
 
+44 (0)20 7679 7817
LMCB Room 3.12
 
Twitter @PichaudLab
Polarity and morphogenesis

Research synopsis

Our goal is to understand how different cell types interact to generate functional tissue organisation during development. This is a longstanding question in biology that largely remains unanswered, especially considering how organs form in vivo.

We are particularly interested in epithelial tissues. These are found in most organs, where they delineate physiological compartments and where they enable selective exchange of gas (lung) or nutrients (intestine), and support fluid detoxification (kidney) and secretion (mammary gland). 

Epithelia have evolved 3D shapes that are best suited for these various physiological functions. They can be stratified to confer optimal protection against external abrasive forces and toxins (e.g. skin), they can form tubular networks to increase surface exchange with the external milieu, or form cysts where fluids can be secreted.

Generating these tissue shapes requires different cell types to coordinate their movement, morphogenesis and polarity in space and time.  Our work aims to establishing the mechanisms and pathways that underpin these morphogenetic processes, and how they are coordinated within a group of cells to pattern a tissue in 3D.   For this we combine molecular and optogenetic approaches in vivo using the genetically amenable eye of Drosophila melanogaster as a physiological system, combined with mammalian 3D cell culture systems, mathematical modelling and state-of-the-art quantitative imaging methods. This multidisciplinary approach to study patterning of a multicellular structure capable of supporting light detection, allows us to reveal how nanomachineries in cells and groups of cells in a tissue, work together to induce 3D tissue organisation during organ development.

A hallmark of cancer is a loss of epithelial tissue architecture and by understanding how 3D organisation of these tissues is established and maintained we hope we can contribute to our understanding of the pathways that promote this disease.  

Pichaud lab research image

Pichaud lab research image

Selected publications

Pichaud F, et al (2019). Regulation of Cdc42 and its effectors in epithelial morphogenesis. Journal of Cell Science 132: jcs217869.
Zihni C, et al (2017). An apical MRCK-driven morphogenetic pathway controls epithelial polarity. Nature Cell Biology 19, 1049-1060.
Walther RF, et al (2016). Pak4 Is Required during Epithelial Polarity Remodeling through Regulating AJ Stability and Bazooka Retention at the ZA. CELL REPORTS, 15 (1), 45-53. doi:10.1016/j.celrep.2016.03.014

 

Funders

Medical Research Council
Wellcome Trust
BBSRC
 

Research themes

Cytoskeleton and cell cortex
Polarity and cell shape
Cell-cell interactions
Membrane trafficking
 

Technology

Light microscopy
Translational research
Bioinformatics
Super-resolution microscopy
Electron microscopy
 

People

Rhian Walther (Investigator Scientist)
Kate Massey (PhD Student)
Jak Sheeran (Masters Student)

Collaborators

Chris Stefan (LMCB, UK)
Yanlan Mao (LMCB, UK)
Ricardo Henrique (LMCB, UK)
Shila Banerjee (UCL, UK)
Roberto Mayor (UCL, UK)
Karl Matter (UCL, UK)
Buzz Baum (MRC LMB, UK)
Francois Schweisguth (Institut Pasteur, France)