We work on three separate research areas:
- Cell and developmental biology (using Drosophila)
- wound healing morphogenesis (using Drosophila)
- the genetics of pathogen resistance (using the zebrafish)


CELL BIOLOGY OF MORPHOGENESIS

Morphogenesis, the shaping of structures in a developing organism, is an aspect of differentiation that is controlled by transcription factors and involves a variety of subcellular effector mechanisms. We study the transcriptional cascade that dictates cell shape changes in the future mesoderm during gastrulation, the role of RNA localisation in the tracheal system, and the role of cell polarity and cell junctions in both systems as well as during wound healing.


DROSOPHILA MESODERM MORPHOGENESIS: cell junctions, cell polarity, cell shape, transcription
The first major morphogenetic event in the Drosophila embryo, an epithelial folding that leads to the invagination of the mesoderm, depends on a transcriptional activator, Twist. We have identified the transcriptional targets of Twist that are responsible for making the epithelial cells in the early embryo change their shapes. Several of these molecules affect the actin cytoskeleton and the adherens junctions that hold the cells together and act as anchors for a contractile acto-myosin network. We arestudying the dynamics and modifications of junctional and cytoskeletal proteins. more.....
One of the Twist targets is the transcriptional repressor Snail. Snail is a regulator of epithelial behaviour during development and cancer. We are using the mesoderm to determine how regulates the disassembly of adherens junctions. Chip-on-chip experiments and expression profiling is used to find early Snail target genes and biochemical and genetic methods are beginning to reveal the junctional modifications that occur during the disassembly of junctions. more.....

Recent publication: Rauzi M. et al. Nature Comm. 2015
, Rembold M. et al., Genes Dev 2014

TRACHEAL MORPHOGENESIS: RNA localisation, vesicle fusion, cell polarity, cell shape

A different type of morphogenetic process, the branching of cells, occurs during the development of the tracheal system which delivers oxygen to all cells of the body. The branched network of the tracheal system in the embryo initially develops according to a stereotypic programme. Later, during larval life, tracheal cells respond to the need for oxygen in the surrounding tissue by sending out long protrusions towards oxygen-starved cells. more.....

Recent publication:Sigurbjörnsdóttir S. et al., Nature Rev. Mol. Cell Biol. 2014.- N. JayaNandanan et al., Nature Comm. 2014

WOUND HEALING MORPHOGENESIS: mechanisms regulating age-associated decline of skin regenerative capacity

A decline in skin regenerative capacity, increased skin fragility with disturbed barrier function and impaired wound healing are leading causes of increasing morbidity and mortality in the elderly. Understanding the underlying molecular and cellular mechanisms is important for the development of strategies to intervene in aging- and disease-associated loss of skin function.
The aim of this project is to understand the role of the nutrition-sensing pathway, and specifically of TOR signalling, in skin homeostasis, regeneration and aging.

Rapamycin inhibits cell growth and is used in the clinic for treating diseases such as cancer. The molecular target of rapamycin, the Ser/Thr kinase TOR, senses and integrates a variety of environmental cues from nutrients and growth factors, acting as a nexus point for cellular signals to control growth and metabolism. 

TOR interacts with several proteins to form two distinct complexes named TOR complex 1 (TORC1) and 2 (TORC2). Altering the activity of components of the TOR pathway either genetically or by pharmaceutical intervention can extend healthy lifespan in laboratory animals. It is not clear to what extent this is due to organ-specific or systemic effects, and indeed in some organs reduction of TOR signalling can be detrimental, and the specific roles of TOR at the cellular level are just beginning to emerge. more

Recent publication: Kakanj P. et al., Nature Comm. 2016 - Ding X. et al., Nature Comm. 2016 ,

 

 

INNATE IMMUNITY IN THE ZEBRAFISH: interferon signalling, inflammation, novel immune recognition molecules

Differential resistance to pathogens provides a strong selective force in evolution. In vertebrates, both the adaptive immune system and natural immunity defend the organism against pathogens. The biology of the adaptive immune system is well understood, and natural immunity is beginning to be widely studied, but the contributions of these defence systems to selection in the wild have not been fully investigated, more .....

Recent publication: Howe K. et al., Open Biology 2016 - Kuri P. et al., J. Cell Sci. 2016 - Aggad, D. et al., J. Immunology 2010