2005-05-11
MULTIFUNCTIONAL APPROACHES TO UNDERSTANDING CRANIOFACIAL ABNORMALITIES

Job Title Marie Curie Host Fellowships for Early Stage Research (PhD) Training

2 EU funded Early-Stage Researcher/Visiting Fellowships are available commencing October 2005 in the 5** research department of Craniofacial Development. The training will encompass various aspects of craniofacial biology relating to development and craniofacial abnormalities. This will substantially increase our understanding of normal development of the craniofacial skeleton in addition to identifying mechanisms of skeletal pathologies. Fellows will undertake their research training via a PhD programme in an interactive environment and in addition to receiving specialised laboratory training, will attend tutorial courses and technical training days at the forefront of scientific research. The available projects, together with the supervisor names and project outlines, are listed below.

o Regulation of craniofacial skeletal differentiation – Dr Philippa Francis-West (CFD1)
The head is probably one of the most complex regions of the body, and its development exhibits a number of unique characteristics. This project will focus on the development of craniofacial skeletal structures, comparing their molecular, cell and tissue regulation of development to that of the axial skeletal structures which, unlike skeletal development in the head, is extremely well characterised. The project will take gain and loss of function approaches using the developing chick embryos as a model system. These will include tissue recombination studies in vitro, molecular biology analyses and in vivo manipulations such as the misexpression of factors using replication competent retroviruses. Thus, the fellow will be trained in a wide range of techniques including embryonic manipulation, molecular biology and tissue culture. The student will join an interactive group, which also has a number of active collaborations both nationally and internationally.

o Differentiation of bone and cartilage cells by embryonic stem cells - Dr Agi Grigoriadis (CFD5)
Elucidating the mechanisms controlling the differentiation of embryonic and adult stem cells to bone and cartilage cell lineages is of fundamental importance for understanding not only the normal development of the craniofacial skeleton, but also for identifying the mechanisms of skeletal pathologies such as craniofacial disorders, chondrodysplasias, metabolic bone disease and skeletal malignancies. The aims of this project are to investigate the transcription factors and signalling molecules that control the commitment and differentiation of embryonic stem (ES) cells to the osteogenic and chondrogenic lineages, focusing on the AP-1 transcription factor and Rho GTPases (see selected references).
1. Grigoriadis, A.E., Wang, Z.-Q., Cecchini, M.G., Hofstetter, W., Felix, R., Fleisch, H.A. and Wagner, E.F. 1994. c-Fos is a key regulator of osteoclast/macrophage lineage determination and bone remodeling. Science, 266: 443-448.
2. Grigoriadis, A.E., Wang, Z.-Q. and Wagner, E.F. 1995. Fos and bone cell development: Lessons from a nuclear oncogene. Trends Genet., 11: 436-441.
3. Thomas, D.P., Sunters, A., Gentry, A. and Grigoriadis, A.E. 2000. Inhibition of chondrogenesis in vitro by constitutive and inducible overexpression of the c-Fos proto-oncogene. J. Cell Sci. 113: 439-450.
4. Sunters, A., Thomas, D.P., Yeudall, W.A. and Grigoriadis, A.E. 2004. Accelerated cell cycle progression in osteoblasts overexpressing the c-fos proto-oncogene: Induction of cyclin A and enhanced CDK2 activity. J. Biol. Chem. 279: 9882-9891.
5.. Harmey, D., Stenbeck, G., Nobes, C.D., Lax, A.J. and Grigoriadis, A.E. 2004. Regulation of osteoblast differentiation by Pasteurella Multocida Toxin (PMT): A role for Rho GTPase in bone formation. J. Bone Mineral Res. 19: 661-670.

The deadline for applications is the 31st May, 2005 and interviews will be held shortly after. Applications should be made to Bethan Thomas via e-mail (bethan.thomas@kcl.ac.uk). A full CV is required together with a statement of research interests.
(KC)