At this time we are particularly recruiting research postgraduates for the Area of Excellence in Developmental Genomics and Skeletal Research (AoE):

Research Postgraduate Recruitment for the AoE

Applications are invited for postgraduate studies under the 2004 funded AoE programme Developmental Genomics & Skeletal Research. This programme focuses on key issues at the frontier of developmental biology and skeletal research related to the formation and growth of cartilage and bone and the maintenance of skeletal function.

One part of the programme aims at aim to understand genes, pathways and networks regulating cartilage formation and maturation in skeletal growth, through studying transcriptional regulation of chondrocyte differentiation and proliferation; molecular control of terminal differentiation and cell death in chondrocytes; the role of the ECM, its interactions and turnover, in skeletal growth.

Another part of the programme aims to understand molecular mechanisms underlying skeletal disorders – both developmental and degenerative. One area of focus in the programme is to study the impact of unfolded proteins on chondrocyte differentiation. The assembly and folding of secreted proteins in the endoplasmic reticulum (ER) is exquisitely regulated by a complex mechanism that maintains an equilibrium between folded and unfolded proteins. Perturbation of this homeostasis induces ER stress, which, if not alleviated through ER stress signaling (ERSS), ultimately triggers cell death. Identifying strategies taken by cells in vivo to adapt and survive when experiencing ER stress is fundamental to understanding protein folding and secretion disorders . Normal bone growth occurs through a highly coordinated differentiation program that yields specialized cartilage cells (chondrocytes); when this program is disrupted, chondrodysplasia, or malformed skeletons, can result. Chondrodysplasias caused by mutations that affect protein assembly and secretion are characterized by a disorganization of bony growth plates and distension of the ER. In a recent study (1) we tested whether these chondrodysplasia characteristics were linked to ERSS. By investigating the impact of ER stress on the cell fate of hypertrophic chondrocytes (HCs) in transgenic mice expressing mutations in collagen that prevent proper folding, we revealed a novel adaptive mechanism that helps alleviate the unfolded protein load. Instead of undergoing apoptosis, the HCs undergoing ER stress adapt, re-enter the cell cycle, and revert to a less-mature state in which expression of the mutant collagen is reduced.

Degenerative intervertebral disc disease (DDD) and its subsequent herniation is a common cause of back pain and sciatica. The development of DDD is complex but thought to be an effect of ageing and related environmental factors such as occupation, sports activities, injury and smoking. Association study of DDD in twins suggests that environmental effects are modest and that it can be explained primarily by genetic influences . It is important to determine the genetic factors associated with DDD.

The following MPhil/PhD projects under the AoE programme are available for application :

Reference

1. K. Y. Tsang, D. Chan, D. Cheslett, W. C. W. Chan, C. L. So, I. G. Melhado, T. W. Y. Chan, K.M. Kwan, E.B. Hunziker, Y. Yamada, J. F. Bateman, K. M. C. Cheung, K.S. E. Cheah**. Surviving ER Stress Is Coupled to Altered Chondrocyte Differentiation and Function PLoS Biology (2007) Feb 13;5(3):e44

Interested candidates should send their curriculum vitae to the AoE Director, Prof. K.S.E. Cheah at biochem@hkusua.hku.hk who may also be contacted for further information on the projects.