Advances in proteomics have constantly altered our understanding of cell biology and biochemistry by providing new approaches and techniques to identify complex proteomes, protein-protein interactions and post-translational modifications. Additionally, proteomic approaches are believed to have enormous potential for discovery of disease biomarkers that can provide diagnostic, prognostic and therapeutic targets and address important problems in clinical and translational research. Unfortunately, to date the development of new assays based on biomarkers discovered by proteomics has been unsuccessful mostly due to low sensitivity and specificity of various candidate biomarkers.
Stem cells have two important characteristics that distinguish them from other cells: the ability to self-renew through cell division for a prolonged period, and to differentiate into multiple cells with specialised functions. The power of stem cells for tissue development, regeneration and renewal has been well known to embryologists for many years. The recent concept of adult tissue stem cells as pluripotent progenitors for various tissues has led to the rapid expansion of stem cell research.
A number of sophisticated approaches have been developed to study the structure and function of genes, including the whole-scale sequencing of entire organisms, global transcriptional profiling, and forward genetic studies. However, these techniques are ultimately limited by the fact that they only assess intermediates on the way to the protein products of genes that ultimately regulate biological processes.
While scientific discoveries can be turned into financial assets, the scientific process itself has proven difficult to harness to efficiently create marketed products bringing profits. This translation is especially challenging for the pharmaceutical and biotechnology industries owing to the tremendous complexity of biological systems.
Recent years have seen great upward leaps in the development of mass spectrometry applied to the field of proteomics. Today it is possible to take a complex biological sample such as organelles, cells, tissue or a biofluid, perturbed or stimulated in some way, and identify and quantitate up to several thousand proteins and determine the level of relative change caused by the perturbation or stimulus. The current challenge is not to identify or quantitate proteins in a limited set of samples, but to profile large series (clinical samples, time-course, sub-cellular compartments) at sufficient depth, and to interpret and make biological sense of the data.
The complexity of drug discovery faces many challenges; principally, the failure of drug candidates during the development process as a result of adverse effects or lack of efficacy. A key reason for this high attrition rate is that we are only just beginning to understand the complexity of the response(s) from a biological system to perturbations, such as a disease state or drug treatment. Subsequently, a deeper insight into the molecular mechanisms underlying both disease processes and drug action will ultimately contribute to increased productivity through the drug discovery process.
Large scale techniques, such as combinatorial chemistry, high throughput screening and the various "omics" techniques, have largely entered the pharmaceutical and diagnosis industry besides the more classical and targeted approaches. Among these large scale techniques, proteomics is one for which there seems to be a widening gap between what is expected and what has been delivered to date, resulting in a strong questioning of the position and usefulness of proteomics in this industry.
Within a decade proteomics has evolved from a fledgling discipline reserved for specialised laboratories, to a firm fixture in our standard omics arsenal used routinely by the research community. This stunning progress is due to many factors; the finishing of the genome projects provided major intellectual motivation and the development of better and much easier to use mass spectrometry (MS) instruments were technological drivers. What is even more remarkable is that this progress has been made despite leaving some main issues in proteomics unsolved. Besides these known boundaries, it also has revealed new frontiers and new interesting glimpses into the world beyond. This essay discusses some selected issues, but cannot necessarily be exhaustive or free of personal opinion.
Until recently the use of proteomics in the biomedical arena has included programmes aimed at the elucidation of cellular responses to extracellular stimuli by known and potential drugs. It has been anticipated that these will lead to the elucidation of the basic mechanisms of cellular responses, potential identification of new drug targets and discovery of the mechanism of action of drugs both NCE’s and those currently in development.
Protein chip technology is essential for high through-put functional proteomics. In this review the development of a novel protein tag consisting of five tandem cysteine repeats (Cys-tag) at C-terminus of proteins which was covalently attached to the surface of a maleimide-modified diamond-like carbon-coated silicon chip substrate is described.
Over the last ten years the Proteomics field has been a technologically dynamic area. New methods and techniques help drive the field to achieve more sophisticated measurements that yield increasingly larger volumes of data and information. This creates several problems.
The development of proteomics has been based very heavily on the suite of analytical techniques encompassed by mass spectrometry and associated methods. It is therefore appropriate that the work of the Michael Barber Centre for Mass Spectrometry (MBCMS, named for the inventor of, inter alia, the fast atom bombardment ionisation method) should now be largely driven by the needs of proteomics research and the broader field of systems biology.
The investigation of functional protein-protein interactions has been gaining momentum with recent technological innovations. The high-throughput era in genomics and proteomics research is essentially dependent on technological advancements to drastically increase capacities in both large-scale gathering of data; their interpretation and functional validation, as well as the compilation and storage of data in a standardised format. Contributions of the European Commission-funded ‘Interaction Proteome’, an integrated project in the field, are outlined in this article.
The American Society for Mass Spectrometry (ASMS) will be holding its annual conference later this month where approximately 6,000 scientists will gather to learn and share the latest in mass spectrometry technologies.
The human blood plasma harbors treasure, which, like most treasures, is not easily attained, and finding it requires ingenuity, endurance and possibly a grain of luck. The blood plasma is the largest (most proteins) and deepest (widest dynamic range) of the human proteomes. In order to ‘triumph over’ it, it is necessary to overcome an enormous protein concentration range to finally be rewarded with the possible discovery of biomarkers. But is this a realistic challenge we are facing or is this plasma pool too deep to explore?
Following in the footsteps of two previously successful years, the third annual meeting of the British Society for Proteome Research is organised in conjunction with the European Bioinformatics Institute (EBI).
n the last decade proteomics has revolutionised biology and now biology starts revolutionising proteomics.
To date, hazard/risk assessment of new drugs and chemicals primarily relies on the investigation of toxicological endpoints from animal studies. In this field, the full range of genomics and proteomics technologies can be used in efforts to uncover the molecular mechanisms at work in response to xenobiotic exposure. These new disciplines, called toxicogenomics and toxicoproteomics, offer several practical benefits.
The proteome analysis started by the Human Proteome Organization (HUPO) is the second big international consortium project after the sequencing of the human genome by the Human Genome Project (HUGO). The aim of the HUPO Brain Proteome Project (BPP) is to derive in depth knowledge of the brain from analysing samples with state-of-the-art proteomics techniques.
The conclusion of the Genome Sequencing Project – far from providing the solution to the problem of human disease – has created further questions that had not previously been considered. Hence, the age of genomics has initiated the need to examine the body’s real biochemical actors: proteins, to learn about their role in human health and disease.
The availability of the complete sequence of some model organism genomes, including the human genome, offers new opportunities for biological research. The goal is to establish technology to identify all the proteins involved in a particular biological process and the interactions between them.
Less than a week after Nature and Science published the special issues on the ’blueprint‘ for the human genome sequence 15-16 Feb, 2001, the Financial Times of 21 February, 2001, ran a major article about proteomics, calling proteins “the real stuff of life”. Proteins are, indeed, the effector molecules for most cellular actions and interactions. As attention has migrated from genome sequences to genetic variation and functional genomics, proteomics has gradually emerged as a potentially powerful set of technologies for biomarker discovery and mechanistic studies important to drug development and drug safety surveillance.
The past decade has witnessed an explosion in the field of proteomics. This development has been driven by the development of database search algorithms, expansion of sequence databases and improvements in mass spectrometry instrumentation. Quantitative techniques using isotopic dilution have allowed quantitative experiments. The expanding opportunities have propelled the development of core facilities to provide services to biological researchers wishing to conduct proteomic experiments for themselves.
The Réseau Protéomique de Montréal Proteomic Network (RPMPN) was created in the year 2000 through funding from Genome Canada, Genome Québec and the Canadian Foundation for Innovation. For the past five years, the RPMPN has been involved in the Cell Map Project, which involves cell biologists from the Université de Montréal and McGill University. The goal is to achieve the most exhaustive documentation (identification, localisation and function) of protein expressed in mammalian organelles challenged with hormones such as insulin and EGF, along with their respective control.
