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Postdoc Position Available

Position: Post doctoral associate

Focus: craniofacial development and anatomy, morphometrics, image analysis, developmental genetics

We are looking for excellent post doctoral researchers to work on a large collaborative project concerning the genetics of craniosynostosis and normal craniofacial development. The project, funded by the National Institutes of Craniofacial and Dental Research of NIH, seeks to understand the developmental basis of craniosynostosis and shed light on the interaction of skeletal and neural tissue in the development and evolution of neurocranial shape. The data needed to obtain our stated goals require the collection of landmark coordinate data from large samples of micro-computed tomography (CT) scans of embryonic mouse skulls with known genetic mutations and micro-magnetic resonance images of their brains. The post doctoral associate will be responsible for the collection of the cranial data sets from the micro-CT images, but will be involved in other aspects of the project including the collection of alternate skeletal data sets, the study of embryonic neural development, quantitative analysis of morphological and genetic data, meetings among collaborators, manuscript preparation, and further grant writing. Experience and interest in developmental biology and genetics, image analysis, craniofacial anatomy, or molecular laboratory methods is desired, but not required. We are looking for someone deeply interested in applying modern technologies and methods to the understanding of the developmental processes involved in the production of craniosynostosis as well as craniofacial evolution. Applicants should send a current curriculum vita, a statement of research interest and experience, and a list of three references to Joan Richtsmeier via email:jta10@psu.edu. Earliest start date: April 1, 2008. Institution: The Pennsylvania State University (http://www.psu.edu/) Location: State College, PA (http://www.statecollege.com/). Salary: commensurate with experience at NIH levels. Duration of appointment: one year with 4 additional years possible depending upon funding. For more information on the lab and the project go to Project summary below or explore our lab website: http://getahead.psu.edu

Penn State is committed to affirmative action, equal opportunity and the diversity of its workforce.

Project Summary:

Craniosynostosis, the premature fusion of one or more cranial sutures, is a common malformation occurring in 1 out of every 2500 live births and shows marked variation of phenotypes. The skull shape in craniosynostosis can not be explained simply by the premature fusion of sutures, but involves widespread abnormal development of the head. A number of mutations have now been identified that are associated with certain clinically defined craniosynostosis conditions. Eight of the craniosynostosis disorders including Crouzon, Apert and Pfeiffer syndromes are caused by mutations in fibroblast growth factor receptors (FGFR)-1, -2 or -3. FGFR tyrosine kinases and their ligands play fundamental and widespread roles in development and are known to play a crucial role in the control of cell migration, proliferation, differentiation and survival by activation of multiple pathways and interaction among signaling pathways. Importantly, FGFRs are involved in development of the skull, meninges, and the brain.

               We propose a unifying study of molecular and morphological research aimed at identifying the intermediate developmental steps in the genotype-phenotype continuum of craniosynostosis. Ours is a “phenogenetic” approach that attempts to connect biological phenotypes with their underlying genetic processes such as regional differentiation by activation of signaling. Through a study of archived MR and CT images of humans with isolated craniosynostosis we defined phenotypic correlations of traits on skull and brain in isolated and syndromic craniosynostosis. These correlations are indicative of strong developmental associations between brain and skull. These associations will be further tested using additional 3D data from CT and MR images of cases of coronal craniosynostosis and Apert, Crouzon and Pfeiffer syndromes and micro-CT and micro-MR of two Fgfr2 mouse models for these syndromes. Using anatomical sites identified by our investigations of human skull and brain covariation as a temporal and spatial guide, we will document patterns of abnormal proliferation, differentiation, apoptosis, and Fgf/Fgfr signaling in developing cranial tissues of Fgfr2+/S252W and FgfrcC342Y/+ mutant mice at three developmental stages. Our hypothesis is that the spatiotemporal map of abnormal Fgf/Fgfr signaling in formative skull and brain is the basis for a series of developmental events that result in anomalous cellular processes local to those sites and ultimately result in the abnormal head and brain shape in craniosynostosis. Our morphological analyses will inform our molecular investigations of how two particular mutations affect phenogenetic processes to produce developmental relationships that lead to craniosynostosis phenotypes.