Biology meets industry – genomics, proteomics, phenomicsThis topic is sponsored by the Australian Proteome Analysis Facility and the Australian Phenomics Facility. The entry of information technology and robotics into the biology laboratory is opening the door to new ways of studying cell biology – the 'omics. Key text Key text'Omics is a general term used to describe a rapidly growing family of biological sciences – the most famous member of which is genomics. Genomics is the study of a genome (the total genetic material of an individual or species), rather than the study of an individual gene. For most of the last decade, genomics, and especially the Human Genome Project, have never been far from the headlines. However, even before the announcement in February 2001 that the sequencing of the human genome had been completed, the principles and technologies which had enabled this impressive achievement were being turned to the study of other areas of cell biology. What are the 'omics?
Industry enters the lab The emergence of the 'omics has been made possible by advances in information technology and robotics. These technological improvements have allowed researchers to automate processes which previously had to be carried out by hand on the laboratory bench. Rather than studying one gene or protein at a time, this high-speed assembly-line approach permits huge amounts of data to be collected and stored in databases, to be analysed later. For example, the mapping of the human genome means we now have the DNA sequence of every human gene – however, we don't yet know what each gene does. It's analogous to having a map without all the place names on it. Now the race is on to uncover which proteins each gene codes for and what these proteins all do. Proteomics – the next big thing While the genome may be the blueprint for an organism, proteins are the structural and functional molecules required by virtually all life processes. Therefore, to truly understand how an organism functions we need to understand more than just its genome – we need to understand the proteome and all the other 'omes' as well. For this reason, proteomics is one of the fastest-growing areas of biological research now that the human genome has been mapped. However, unveiling the proteome is not as straightforward as it might appear. Some of the challenges faced by proteome researchers are outlined in Box 1: Unveiling the proteome. Australia has a strong history in proteomics research – Australians pioneered the science, and the term itself was even coined by researchers at Macquarie University in Sydney. While researchers in many other countries were focused on the genome, a number of Australian groups were concentrating on the fledgling science of the proteome. A new frontier in medicine Understanding what all the proteins in the body are and precisely what they do will give researchers a powerful new tool for diagnosis and treatment of disease. Many diseases are a result of defective genes, which create defective proteins (or no protein at all) that go on to cause problems for the organism. By being able to pinpoint the source of the disease, new treatments can be designed which precisely address the cause. For instance, treatments might be designed to specifically target the area of an abnormal protein which is causing dysfunction. Or, where insufficient production of an essential protein is the cause, artificially produced versions of the identified protein might be used to treat the illness – just as the protein insulin is used to treat diabetes. Australian innovations in the field are already being utilised in pharmaceuticals and agricultural products – the anti-arthritis drug Remicade, for example, is based on a specific antibody patented by the Australian company Peptech (Box 2: Case study – Remicade and Glivec). The 'omics also raise the prospect of personalised or targeted medicine – where the specific markers which distinguish an individual's disease can be identified and a treatment created to correct it. Because of the focused nature of this approach, adverse side effects can be reduced and treatment effectiveness improved. An example of this kind of targeted medicine is the anti-cancer drug Glivec (Box 2: Case study – Remicade and Glivec). Another aspect of personalised medicine is the potential to identify the specific gene variations a patient carries and using the knowledge to prescribe drugs known to be safe and effective for someone with their genotype. Currently, adverse drug responses occur in a significant proportion of patients, and determining the most effective pharmaceutical for an individual involves a lot of trial and error. This same technology could be used to predict a person's risk of suffering from diseases with a genetic component, such as heart disease or cancer, in a much more precise way than current predictive methods. Ethical ramifications and other problems Despite all the potential benefits, there are also some serious social issues that will emerge as a result of this new technology. For example, the ability to accurately predict a person's individual risk of disease with an easy genetic test raises the prospect of health insurance companies insisting on such tests before issuing a policy – and even refusing to cover those who have a heightened genetic risk for say, heart disease or breast cancer. Another problem is that personalised medicine and targeted drug treatments are currently very expensive. Many patients will be unable to afford such treatments on their own, and governments are already faced with difficult choices about which life-saving or life-improving drugs they can afford to subsidise. With many more such treatments on the horizon – and with a Pharmaceutical Benefits Scheme that is costing Australia nearly $5 billion dollars a year – the issue of which new treatments the government can afford to subsidise will only grow in importance.
Box 1. Unveiling the proteomeIf sequencing the human genome was a massive undertaking, consider some of the challenges involved in creating a map of the human proteome: Firstly, there are far more proteins in an organism than there are genes. Part of the reason for this is that messenger RNA (mRNA), the mobile copy of DNA which is used as a template when a cell creates a protein, can undergo 'editing' after it is first copied. Segments of the RNA can be removed before a protein is created from it, meaning a number of different proteins can be created from the same gene. Even after the protein has been translated from the mRNA it can still undergo numerous transformations including the addition of chemical groups, the removal of sections of the protein, and combination with other proteins – any of which can alter the form and function of the finished molecule. An extreme example is a fruit fly gene which was discovered by scientists to code for 38,000 different proteins! So while we now know that humans have approximately 30,000 genes, our total number of proteins is still unknown – although estimates put the total at 100,000 or more. Secondly, while the genome remains relatively static in any given cell in an organism, the expression of the proteome changes from cell to cell and from moment to moment. Age, gender, health, and recent consumption of food or drugs all affect the proteome – the same cell, if examined at different times or under different conditions, can be expressing a different complement of proteins. Thirdly, cells from different tissues within the same organism express distinct sets of proteins. These and other factors involved in making a map of the human proteome present a challenge worthy of the potential rewards it might offer.
Box 2. Case study – Remicade and GlivecGlivec is a molecularly targeted drug treatment for chronic myeloid leukemia (CML), manufactured by the pharmaceutical company Novartis. It operates by blocking the specific signal transduction pathway that is abnormally activated in leukemic cells. Blocking the pathway prevents the uncontrolled proliferation of white blood cells that characterises the deadly cancer. A primary difference between Glivec and more conventional forms of cancer treatment such as radiotherapy and chemotherapy is that Glivec specificially targets the defective pathway which causes the disease. Radiotherapy and chemotherapy are toxic to all the body's tissues, but are effective cancer treatments because fast-dividing cancer cells are more susceptible than normal healthy cells. However, the toxicity to healthy cells results in serious side-effects for the patient. Research into a targeted treatment for the cancer was made possible when researchers at the California Institute of Technology in the 1980s discovered that a single defective protein (a tyrosine kinase enzyme) could cause CML – this made it a potential candidate for a targeted treatment. By the mid-to-late 1990s, researchers had developed from a promising but weak-acting inhibitor class of molecules a powerful, specific inhibitor that could inhibit the abnormal cell pathway. Glivec has proven to be a very effective treatment for the disease, and trials are underway to determine its effectiveness against other forms of cancer. A primary drawback to the treatment is its cost – a year's treatment with Glivec costs around $50,000. The drug is listed under the Commonwealth Government Pharmaceutical Benefits Scheme in Australia, making it affordable for sufferers. It was first approved for subsidy in 2001 for some patients with CML. Coverage has since been expanded, and Glivec is now subsidised as a first-line treatment against the early, chronic stages of CML. Remicade is a drug designed to treat certain autoimmune diseases, especially rheumatoid arthritis and Crohn's disease. It uses monoclonal antibody technology to produce a specific antibody (patented by Australian biotech company Peptech). The antibody blocks the action of the protein Tumour Necrosis Factor Alpha (TNF-α). TNF-α is a powerful regulator of the body's inflammatory immune response which is overproduced in sufferers of rheumatoid arthritis and other auto-immune diseases. Remicade was registered in Australia in August 2000, but was denied listing on the PBS until November 2003. While slightly less expensive than Glivec (at $20,000 per year) there are more sufferers, and the total cost to the PBS is higher. The delay in approving subsidy of the drug is illustrative of the difficult decisions government bodies will have to make about these new technologies – especially in weighing up expensive treatments that, while not life-saving, can have a tremendous impact on a patient's quality of life. Related site
Activities
Further readingAustralasian Science September 2003, pages 38-40 The common thread (by Stephen Luntz) An interview with Sir John Sulston about how close society came to losing control over ownership of our genes.
August 2003, pages 20-22 The legal helix (by Matthew Rimmer) Explains the legal issues over access to human genome sequence data.
Ecos No. 114, 2003, pages 20-23 Pioneering proteins (by Steve Davidson) Describes different areas of proteomics and how they might be used.
Issues June 2005, pages 23-24 Genetic privacy (by Loane Skene) Discusses new genetic technologies and questions about confidentiality of medical information.
Nature A collection of Nature articles on human genomics is available.
New Scientist A collection of articles on genetics and genes is available.
6 September 2007, pages 8-11 Low-cost personal DNA readings are on the way (by Peter Aldhous) Looks into the availability and the analysis of genetic information.
14 July 2007, pages 42-45 Genomics: Junking the junk DNA (by Aria Pearson) Explores the functions of 'junk DNA'.
21 April 2007, page 15 Monkey genome springs surprise for human origins (by Bob Holmes) Looks at what makes us human.
17 March 2007, pages 44-47 Welcome to life on the tiniest scales (by Henry Nicholls) Looks at how metagenomics is being used to investigate the diversity of microbes.
6 December 2006 Genomic atlas of the mouse brain revealed (by Peter Aldhous) Reports on a genomic atlas of the mouse brain.
25 October 2006, page 13 Honeybees have their genome sequenced (by Bob Holmes) Announces the sequencing of the honeybee genome and some early observations about it.
8 April 2006, pages 38-41 Magic numbers (by Bob Holmes) Looks at the role of chromosome deletions or duplications – gene copy number – in diseases.
19 November 2005, page 54 Junk DNA The human genome sequence suggests there may be an important role for ‘junk’ DNA.
19 July 2003, page 21 DIY approach to drug discovery (Rachel Nowark) Reports on a chemical genomics project that would allow academics to carry out early stages of drug development as part of existing research.
Inside Science (No. 138), 17 February 2001 Genes, the genome and disease (by Kate Bendall) Explains DNA, genes and bioinformatics and how research in these areas could lead to new medical treatments.
RTD Info April 2005 DNA: life's memory The hundreds of millions of chemical letters in a genome sequence hold the memory of the evolution that led to a species' appearance. The skill lies in deciphering them.
Scientific American May 2008, pages 11-12 Are personal genome scans medically useless? (by Sally Lehrman) Argues that DNA scans may not improve health.
18 February 2007 Largest ever autism study identifies two genetic culprits (by Nikhil Swaminathan) Discusses the finding that two regions of the genome may trigger the disease.
December 2006, page 35 DNA sequencing on the cheap (Charles Choi) Reports on low cost DNA sequencing technology.
December 2003, pages 78-85 The unseen genome: beyond DNA (by W. Wayt Gibbs) This article on epigenetics explains the approach taken in phenomics.
April 2002, pages 26-33 Proteins rule (by Carol Ezzell) Describes proteomics and explains how the field relates to drug development.
February 2002, pages 34-41 The magic of microarrays (by Stephen H. Friend and Roland B. Stoughton) Explains what microarrays (gene chips) are and how their diagnostic information can help to provide individualised therapies.
Useful sitesMeet the 'omics (Saskatchewan Agricultural Biotechnology Information Centre, Canada) General descriptions of a number of the 'omics.
Gene hunt is on for drought resistance (Australian Broadcasting Corporation, Science Online) Looks at how researchers are using functional genomic and proteomics
to identify genes that control drought resistance in wheat and barley.
Annotation marathon validates 21,037 human genes (Public Library of Science, USA) Describes one of the latest efforts to make a functional description
of the human genome.
The Human Genome (Wellcome Trust, UK)
Biotechnology in medicines (Biotechnology Australia) Fact sheet that looks at how biotechnology is currently being used in
medical research and also addresses some of the issues surrounding this
research.
Australian Broadcasting Corporation (transcripts)
Ask the experts – What is junk DNA, and what is it worth? (Scientific American)
Researches the function of the noncoding portions of a genome.
Glossarygene. The basic unit of inheritance. A gene is a segment of DNA that specifies the structure of a protein or an RNA molecule. genotype. The particular set of genes carried by an individual organism. insulin. A hormone produced by special cells in the pancreas. Insulin allows glucose to enter the body's cells, where it is used as an energy source. In type 1 diabetes (insulin-dependent diabetes) the body does not produce insulin, causing glucose to build up in the blood, giving high blood sugar levels. Type 1 diabetics can't make their own insulin so they must inject it every day. For more information see Type 1 diabetes (Medline Plus Medical Encyclopedia, US National Library of Medicine and the National Institutes of Health). messenger RNA. RNA molecule that is transcribed from DNA and is used to direct the synthesis of a protein. phenotype. The observable characteristics of an individual. The expression of these characteristics results from the interaction of genetic and environmental factors. signal transduction pathway. A series of steps by which a signal outside the cell causes a functional change inside the cell. Signal transduction pathways are important means of regulating numerous cellular functions in response to changes in the cell's chemical or physical environment. External sites are not endorsed by the Australian Academy of Science. The Australian Foundation for Science is a supporter of Nova. Posted July 2004.
This topic is sponsored by the Australian
Proteome Analysis Facility and the Australian
Phenomics Facility.
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