research

craniofacial research

summary

Our research focuses on understanding how early development of the face and limbs is controlled. Birth defects that result in malformation of the face and limbs are common and in most cases the causes of these conditions are unknown. We use animal models and human genetics to determine how normal development is controlled and how genetic changes in these processes cause birth defects of the face and limbs.

group leader(s)

Peter _farlie _03 Dr Peter Farlie
Craniofacial Research
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville Victoria 3052

T +61 3 8341 6409
F +61 3 9345 5834
E peter.farlie@mcri.edu.au

group leader biography

current research projects

Project 1: Analysis of mouse models of human birth defects

Birth defects involving the face affect approximately 1% of all babies but the genes involved in most of these conditions are unknown. ENU mutagenesis is a forward genetics approach that allows phenotypes of interest to be identified without any prior knowledge of specific genes involved in the development of the organ system of interest. Once useful phenotypes are established, rapid gene mapping approaches have been developed to identify the mutated gene. We have a number of mouse strains harbouring birth defects involving both the face and limbs that appear similar to human syndromes. Identification of the mutated genes in these strains will help us understand how the normal developmental program is altered in human birth defects and will facilitate identification of disease genes in humans.

This project will provide an opportunity to learn advanced developmental biology approaches to understanding human birth defects and gain skills in a wide range of molecular biology techniques. Upon completion of this project, students will be in a strong position to initiate their own research into the genetic and developmental basis of human birth defects.

Project 2: Large-scale screen of genes controlling skeletal development

Congenital defects of the skeleton are common and have a major impact on health and well being of affected children. Microarray RNA expression Syndromes affecting the face have an enormous impact on the individual and their families. We are working to understand how these conditions are caused by analysing the genomes of affected individuals. We are concentrating on a number of well known conditions such as cleft palate, Pierre Robin sequence (PRS) and Goldenhar syndrome. PRS is a common craniofacial disorder consisting of small lower jaw, posteriorly placed tongue and cleft secondary palate.

These defects lead to serious feeding and respiratory difficulties in infants. The underlying cause is thought to involve inadequate growth of the facial skeleton during embryonic stages. Along with our international collaborators we have identified alterations in regulatory elements controlling the expression of the Sox9 gene associated with PRS. We are continuing to investigate the role of these genetic changes in occurrence of PRS. Goldenhar syndrome is a hemifacial microsomia (one side of the face is too small) that also involves ear and vertebral defects. This condition is usually sporadic but we have identified a number of families in which Goldenhar syndrome appears to inherited in a dominant manner. We have generated a mouse model of Goldenhar syndrome and are using deep sequencing approaches to determine how this condition occurs.

team members

Casey Ah-Cann - Honours Student (UoM Paeds)
Mohamad Azanan - Honours Student (UoM Paeds)
Andrea Bialocerkowski - HONORARY RESEARCH FELLOW
Heather Cleland - HONORARY RESEARCH FELLOW
Joanne Fifer - Research Assistant
Anil Jugessur - HONORARY RESEARCH FELLOW
Kerry Miller - Postdoctoral Fellow
Anthony Penington - Honorary Research Fellow
Tiong Tan - Research Officer
Megan Welfare - Research Assistant

publications

Gordon CT., Wade C., Brinas I., Farlie PG. CXCL14 expression during chick embryonic development. International Journal of Developmental Biology 55 (3) : 335 - 340(2011) PubMed
Jugessur A., Shi M., Gjessing HK., Lie RT., Wilcox AJ., Weinberg CR., Christensen K., Boyles AL., Daack-Hirsch S., Nguyen TT., Christiansen L., Lidral AC., Murray JC. Fetal Genetic Risk of Isolated Cleft Lip Only versus Isolated Cleft Lip and Palate: A Subphenotype Analysis using Two Population-Based Studies of Orofacial Clefts in Scandinavia. BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY 91 (2) : 85 - 92(2011) PubMed
Manji SS., Miller KA., Williams LH., Andreasen L., Siboe M., Rose E., Bahlo M., Kuiper M., Dahl HH. An ENU-Induced Mutation of Cdh23 Causes Congenital Hearing Loss, but No Vestibular Dysfunction, in Mice. American Journal of Pathology 179 (2) : 903 - 914(2011) PubMed
Manji SSM., Williams LH., Miller KA., Ooms LM., Bahlo M., Mitchell CA., Dahl HHM. A Mutation in Synaptojanin 2 Causes Progressive Hearing Loss in the ENU-Mutagenised Mouse Strain Mozart. PLOS ONE 6 (3) (2011) PubMed
Tan TY., Collins A., James PA., McGillivray G., Stark Z., Gordon CT., Leventer RJ., Pope K., Forbes R., Crolla JA., Ganesamoorthy D., Burgess T., Bruno DL., Slater HR., Farlie PG., Amor DJ. Phenotypic Variability of Distal 22q11.2 Copy Number Abnormalities. AMERICAN JOURNAL OF MEDICAL GENETICS PART A (7) : 1623 - 1633(2011) PubMed