Professor David Strutt
Professor of Developmental Genetics
Room: D36 Firth Court
Brief career history
We are interested in the genetic control of animal development and how cells interact to build complex tissues and organs. We focus on the particular problem of how cells coordinate their polarity within developing tissues, and as a model study the phenomenon of planar polarity in epithelia of the fruitfly Drosophila
Understanding mechanisms of coordinated cell polarisation during animal development
Lay summary of research
We are interested in the process of morphogenesis, which is the process by which a body grows and develops to form complex tissues and organ systems. This involves the regulation and coordination of three processes: first, the multiplication of cells; second, the differentiation of the right types of cells in the right positions; third, the correct orientation of cells relative to each other. It is this final process in which we are primarily interested.
As the orientation of cells relative to each other is a fundamental conserved process in animal development, we are able to study it using model experimental systems, in particular the fruitfly Drosophila melanogaster. Using this organism we can easily manipulate the function of genes, which has allowed the identification of a large number of genes that are involved in the coordination of cell orientation.
The aims of our research are to understand how these genes work together and how they are organised into hierarchies. By understanding how the genes act, we hope to be able to intervene to correct developmental diseases caused by dysfunction of the genes, and also gain insights into conditions such as cancer metastasis which involve coordinated changes in cell polarity.
Scientific summary of research
Morphogenesis – the formation of multidimensional structures from cells and groups of cells – is one of the fundamental processes underlying the development of complex multicellular organisms. A key property underlying many morphogenetic processes is the ability of cells to coordinate their polarity within a sheet of cells, a phenomenon referred to as "planar polarity" or "planar cell polarity [PCP]". Planar polarity enables the concerted cell movements and rearrangements necessary to shape tissues, and allows the production of arrays of polarised structures such as hairs and cilia.
Work in the Strutt lab seeks to understand molecular mechanisms of planar polarisation. Our approach is to study two conserved mechanisms, the "core" Frizzled-dependent planar polarity pathway and the Fat/Dachsous pathway. Our goal is to dissect the feedback and cell-cell communication mechanisms that mediate coordinated cellular symmetry breaking, and ask how this can be aligned with the axes of tissues.
We exploit the traditional strengths of molecular genetic analysis in Drosophila to precisely manipulate gene and protein function in vivo, taking advantage of the minimal genetic redundancy and the easy accessibility of developing tissues. In particular, this system allows us to perform in vivo cell biology, analysing protein dynamics and behaviour in the context of developing tissues. To do this, we employ both conventional high resolution in vivo imaging techniques such as confocal microscopy, methodologies such as FRAP (fluorescence recovery after photobleaching) and also super-resolution microscopy. These in vivo studies of protein behaviour are combined with studies of the biochemical interactions of pathway components, targeted genetic screens to identify novel regulatory factors, and computational modelling.
Our long term goal is a fundamental understanding of how coordinated cell polarisation is achieved through the integrated spatiotemporal interactions of pathway components acting from the molecular (nanometer) to cellular (micrometre) to tissue (millimetre) scales.
Examples of planar polarised structures on the adult cuticle of the fruitfly Drosophila. Top: photomicrograph of an adult wing (left) with inset (right) showing the regular array of planar polarised hairs on the surface of the wing. Bottom: Scanning electron micrograph of an adult eye (left) with inset (right) showing a histologically stained microtome section through the eye revealing the regular planar polarised arrangements of the groups of cells within the eye that form each facet.
Undergraduate and postgraduate taught modules
- Reciprocal action of casein kinase Iε on core planar polarity proteins regulates clustering and asymmetric localisation. eLife, 2019(8). View this article in WRRO
- Retromer Controls Planar Polarity Protein Levels and Asymmetric Localization at Intercellular Junctions. Current Biology, 29(.), 484-491.e6. View this article in WRRO
- Rapid Disruption of Dishevelled Activity Uncovers an Intercellular Role in Maintenance of Prickle in Core Planar Polarity Protein Complexes. Cell Reports, 25(6), 1415-1424.e6. View this article in WRRO
- A Dual Function for Prickle in Regulating Frizzled Stability during Feedback-Dependent Amplification of Planar Polarity. Current Biology, 27(18), 2784-2797.e3. View this article in WRRO
- Robust Asymmetric Localization of Planar Polarity Proteins Is Associated with Organization into Signalosome-like Domains of Variable Stoichiometry.. Cell Rep, 17(10), 2660-2671. View this article in WRRO
- Cellular interpretation of the long-range gradient of Four-jointed activity in the Drosophila wing.. Elife, 4. View this article in WRRO
- Planar polarity specification through asymmetric subcellular localization of Fat and Dachsous.. Curr Biol, 22(10), 907-914.
- Dynamics of core planar polarity protein turnover and stable assembly into discrete membrane subdomains.. Dev Cell, 20(4), 511-525.