The Logan Group
The objectives of our work are to understand how the limbs are formed normally during embryogenesis, the origins and pathology of congenital limb abnormalities and other diseases that effect the function of the musculoskeletal system in humans. Limb defects are the second most common congenital abnormality present in human live births and diseases affecting the musculoskeletal system are a significant clinical problem, particularly in the older population.
Congenital limbs abnormalities can arise from genetic mutations or environmental insults, the teratogenic drug Thalidomide being a notorious example. A revolution in genomic analysis methods has led to the identification of genetic lesions associated with congenital limb defects. While these methods have clearly identified the importance of certain gene loci for normal limb formation, we are just beginning to understand how these genes and the pathways they regulate function during normal limb formation. Furthermore, many genes that function during embryonic limb development are also required throughout life for normal limb tissue maintenance and repair. It is therefore critical to understand the mechanisms they regulate normal limb development and how disruption of these processes cause diseases that affect the development or maintenance of limb elements.
We predominantly use mouse and chick model organisms, but have also used zebrafish and frog. We interrogate gene function using a combination of coordinated gene misexpression and gene deletion experiments, often in more than one model system. In the mouse, we take advantage of gene conditional alleles and a repertoire of Cre deleter transgenics that we have developed ourselves or have collected that give us control over when and where genes of interest are disrupted or activated ectopically. We often include transgene reporters to aid in phenotyping. In the chick, we use genetic techniques to misexpress genes (either retroviral vectors or electroporation or direct application of recombinant proteins or substances) in combination with more classical embryological approaches. We are also developing in vitro techniques as an alternative and complementary approach to our in vivo models. This involves the generation and characterisation of cell lines derived from transgenic reporter mouse lines we have produced and collected and the use of embryonic stem cells and iPSCs techniques.