Actin Dynamics

Research Interests

Actin is one of the most abundant and highly conserved proteins in eukaryotes. Actin monomers can polymerize into filaments, forming the actin cytoskeleton, which controls numerous processes, including the generation and maintenance of cell morphology and polarity, endocytosis, intracellular trafficking, contractility and cell division. As in mammals, Drosophila has six actin genes, whose cycle of polymerization, depolymerization and organization into functional higher-order networks are controlled by a plethora of actin-binding proteins (ABP), strongly conserved between species. Several lines of evidence strongly suggest that in epithelia different actin genes have specialised functions. Moreover, depending of the identity of each epithelium, distinct dynamic actin filament populations could exist. However, in multicellular organisms, the role of a particular actin isoform and its regulation by ABP within an epithelial tissue remain obscure.
Our goal is to understand how cytoskeleton organization is regulated in genetically distinct epithelia to achieve specialized functions. Our research addresses a fundamental aspect of cell biology, but also aims to broaden our understanding of pathogenesis associated with actin dynamics. Indeed, the multitude of proteins and regulatory mechanisms, involved in the dynamics of the actin cycle, makes this system vulnerable to genetic alterations that may cause diseases. The most familiar one is cancer.

We are looking for highly skilled and motivated Master students; Ph.D. students and Postdocs. If you are interested in joining our group, please send a CV and the name of two referees to Florence Janody

Group Members

Catarina Alexandra Pereira	Postdoc
	Tel: 21 440 7918
Beatriz Fernández	Postdoc
	Tel: 21 440 7918
Pedro Gaspar	External Masters Student
	Tel: 21 440 7918
Ana Rita Amândio	Trainee
	Tel: 21 440 7918
Barbara Jezowska	2007 PGD PhD Student
	Tel: 21 446 4514

Research Project

The role of the actin cytoskeleton in tumor formation and metastasis

Most solid tumors arise within the confines of normal epithelia. Aggressive cancer is a multistage process, which involves disruption of a polarised epithelial architecture, loss of proliferation control, resistance to cell death and invasion/metastasis. This transition can be triggered when proper components of the junctional interface are mutated or when the dynamics of the actin microfilament system is affected. Both system are closely interconnected and together promote stabilisation of cell-cell junctions, essential to avoid conflicts among cells within cellular communities, thus, allowing proper development and maintenance of tissue homeostasis. Our goal is to gain insights into how cytoskeleton organisation is regulated to promote a scaffold of sufficient strength to withstand forces that place tension on the cell within different epithelia, and understand how actin dynamics prevents aberrant proliferation and abnormal active cell migration at later stages of the tumoral process.

Funding

Fundação para a Ciência e a Tecnologia (FCT), Portugal
Using Drosophila to understand the molecular control of actin dynamics in aberrant active cell migration

Collaborators

Peter MacCallum Cancer Institute, Melbourne, Australia
PMCI
Helen Richardson

Research Project

The actin cytoskeleton in the control of cell shape and cell fate determination

Despite the fact that epithelium architecture constrains cells in their ability to move, epithelial cells can be engaged in a large number of morphogenetic rearrangements and adopt different repertoires of cell shapes. A striking example of a transient cell shape change occurs in the Drosophila eye disc. An indentation caused by an apical constriction and apical-basal contraction of the cells, known as the morphogenetic furrow (MF), progresses from anterior to posterior across the disc epithelium, driving differentiation. Anterior to the MF, cells divide actively and appear unpatterned. Just posterior to the MF, photoreceptors form and assemble into evenly spaced clusters. Formation of the MF depends on the rearrangement of the actin cytoskeleton and is crucial for differentiation to take place since the signals associated to the MF are required to instruct cells to stop proliferating and enter differentiation. Our goal is to understand how the dynamics of the actin cycle is regulated by eye patterning genes to allow changes in cell shapes in the MF and promote cell differentiation.

Funding

Fundação para a Ciência e a Tecnologia (FCT), Portugal
Molecular control of actin dynamics and change in cell shape in the morphogenetic furrow during Drosophila eye development

Research Project

Role and regulation of the actomyosin cytoskeleton system in sensing mechanical forces

Cell proliferation must be restricted within tissues, first during embryogenesis to allow morphogenesis, and later in adults to maintain homeostasis and prevent tumorigenesis. This property involves the ability of cells to sense their density or numbers and to apply this information to regulate intrinsic cellular processes including growth, division and survival. To respond appropriately, cells must sense not only chemical signals sent by their neighbors but also physical aspects of their environment, including extracellular mechanical stimuli, such as hydrostatic pressure, shear stress, ions but also intercellular tension caused by cell adhesion. Most of the osmotic and other mechanosensitive responses require tethering to force-bearing actin filaments. The actomyosin cytoskeletal network generates forces, that pushes and pulls against the plasma membrane and the intracellular organelles, promoting intracellular mechanical forces that control cell shape and the robustness of cell architecture. Our goal is to understand how the dynamics of the actomyosin cytoskeletal network is regulated to sense physical aspects of their environment through mechanosensors and respond appropriately over time by modulating cell growth and survival.

Funding

Fundação para a Ciência e a Tecnologia (FCT), Portugal
Unit of Developmental Biology funding

Collaborators

Cancer Research UK – London - UK
CR UK
Nicolas Tapon

Publications

(Selected) Update December (2008).

Carrera, I., Janody, F., Leeds N., Duveau F. and Treisman J.E. (2008). Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13 PNAS May 6 105(18) :6640-9

Janody, F. and Treisman, J.E. (2006). Actin Capping Protein alpha prevents extrusion of vestigial-expressing cells in the Drosophila wing disc epithelium. Development 133 :3349-3357

Roignant, J.Y., Hamel, S., Janody, F. and Treisman, J.E. (2006). The novel SAM domain protein Aveugle is required for Raf activation in the Drosophila EGF receptor signaling pathway. Genes and Development 20 :795-806

Janody, F.; Lee, J.D., Jahren, N., Hazelett, D.J., Benlali, A., Muira, G.I., Draskovic, I. and Treisman, J.E. (2004). A mosaic genetic screen reveals distinct roles for trithorax and polycomb group genes in Drosophila eye development. Genetics 166 :187-200

Janody, F.; Martirosyan, Z., Benlali, A. and Treisman, J.E. (2003). Two subunits of the Drosophila mediator complex act together to control cell affinity. Development 130, :3691-3701

Janody, F., Sturny, R., Schaeffer, V., Azou, Y. and Dostatni, N. (2001). Two distinct domains of Bicoid mediate its transcriptional downregulation by the Torso pathway. Development 128 :2281-2290

Janody, F., Reischl, J. and Dostatni, N. (2000). Persistance of hunchback in the terminal region of the Drosophila blastoderm embryo impairs anterior development. Development, 127 :1573-1582

Janody, F., Sturny, R., Catala, F., Desplan, C. and Dostatni, N. (2000). Phosphorylation of Bicoid on MAP-kinase sites: contribution to its interaction with the Torso pathway. Development 127 :279-289

Schaeffer, V., Janody, F., Loss, C., Desplan, C. and Wimmer, E. (1999). Bicoid functions without its TATA-binding protein-associated factor interaction domains Proc. Natl. Acad. Sci. 96 :4461-4466

Sanchez, C., Lachaize, C., Janody, F., Bellon, B., Röder, L., Euzenat, J., Rechenmann, F. and Jacq, B. (1999). Grasping at molecular interactions and genetic networks in Drosophila melanogaster using FlyNets, an Internet database. Nucleic Acids Research 27, No. 1 :89-94