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Genomics
Technologies that look at the genes and proteins of living structures are opening a whole new world of medical research. One of the most famous accomplishments has been the mapping of sequence variation in the human genome. HKU researchers participated in that international project through our Genome Research Centre and are now trying to develop new platforms and systems to carry out detailed analyses of healthy and diseased states.
"The pace of technological progress in genomics has been astounding over the past decade and the trend is set to continue," said Professor P.C. Sham of the Department of Psychiatry and convenor of the Genomics research theme.
New technologies are expected to help scientists amass a comprehensive list of genomic and proteomic changes associated with disease. In the near term this could accelerate the development of new methods for risk prediction and early detection, and in the longer term lead to more effective prevention and treatment.
The Li Ka Shing Faculty of Medicine, Faculty of Science and Faculty of Engineering are co-operating on projects to improve and test new technologies. In addition, the Medical, Law and Arts Faculties are addressing the ethical, legal and social issues that lie behind genomic research.
Whole genome sequencing
The mapping of the human genome has made it easier to study the genetic variations that cause diseases. Most of the effort has focused on common variants that frequently occur in people with the disease in question. However, whole genome sequencing is capable of detecting rare variants that are also factors in illness.
HKU researchers will use sequencing to look for rare variants related to Hirschsprung’s disease, a birth defect of the intestines. "The results should help to determine the effectiveness of this tool for future use at HKU, as well as some of the genetic variations involved in Hirschsprung’s," said Dr M.M. Garcia-Barcelo of the Department of Surgery.
Proteomics
Cancer, cardiovascular and neurological diseases are all associated with ageing and have limited therapeutic cures. HKU researchers are developing a new platform to investigate some of the proteins involved in these diseases, which could help improve detection and treatment.
The advanced quantitative proteomics platform is expected to help identify new biomarkers for human neuroblastoma stem cells, protein markers associated with the progression of schizophrenia and the molecular mechanisms involved in cardiovascular ageing.
"If we can identify ways to detect these diseases at the pre-symptomatic stage, it could help to advance prevention and treatment," said Dr Y. Wang of the Department of Pharmacology and Pharmacy.
Bioinformatics
Computer technology is critical in genome research where an enormous number of calculations need to be made. For example, the three billion DNA pairs in the human genome had to be pieced together from a huge number of short sequences using computing input from centres around the world. The goal now is to enable individuals to have their personal genomes sequenced but, while technological advances are bringing that closer to reality, there are a few obstacles to overcome.
Faster genome sequencing has been made possible by taking short cuts and using smaller strings of DNA, leaving gaps in between. That can be useful when looking at a particular area, but it makes whole genome sequencing more difficult. HKU researchers are trying to address this issue.
"There is going to be a major demand in future for individual genome sequencing and we want to develop more powerful computers and software to make sequencing possible," said Professor F.Y.L. Chin of the Department of Computer Science.
Systems biology
As the populations of many countries get older, demand is growing for the treatment and prevention of age-related diseases. Researchers around the world have been probing the genetics of these diseases, but they tend to focus on individual genes. At HKU scholars want to look at the problem from a systems perspective to see how DNA, RNA and proteins interact.
Their focus is on calorie restriction, which has been shown to extend the lifespans of various organisms, from bacteria to mice. Associated mutations reduce the risk of age-related diseases, such as cancer and Alzheimer’s. "We want to try to understand the underlying protective mechanisms by looking at the interaction of multiple genes and pathways," said Dr J.J. Wang of the Department of Biochemistry.
Ethics and genomic research
Genomic research gives rise to ethical, legal and social issues. At HKU we are working to ensure our researchers are competent in these issues and uphold international ethical standards regarding the protocols, management and uses of genetic information.
We also want to understand the influence of Chinese culture on attitudes to the use of genomic technologies and personal genetic information. "Our earlier research showed acceptance of genomic technologies for disease prevention but not for increasing food supply," said Professor E.C. Hui of the Medical Ethics Unit. This will be investigated further with the aim of contributing to public understanding of genomics.
