Nanobiotechnology and nanomedicine

Nanobiotechnology is a new direction in the technological science, which plays a key role in creation of nanodevices for analysis of living systems on a molecular level. Nanomedicine is the application of nanotechnologies in medicine for maintenance and improvement of human life using the knowledge on human organism at the molecular level. Application of nanoparticles and nanomaterials for the diagnostic and therapeutic purposes is now significantly extended in nanomedicine. Use of nanotechnological approaches and nanomaterials opens new prospects for creation of drugs and systems for their directed delivery. Implementation of optical biosensor, atomic force, nanowire and nanoporous approaches into genomics and proteomics will significantly enhance the sensitivity and accuracy of diagnostics and will shorten the time of diagnostic procedures that will undoubtedly improve the efficiency of medical treatment. The review highlights recent data on application of nanobiotechnologies in the field of diagnostics and creation of new drugs.     

2nd BSPR London Regional Meeting and 6th Annual Imperial Proteomics Day. November 2007, Imperial College London, London, UK

The 2(nd) BSPR London Regional Meeting held at Imperial College London focused on nanoproteomics and single cell proteomics, the solutions to many of the technical challenges in proteomics and protein based molecular diagnostics. This one day meeting included presentations from leading scientists within and outside of Imperial College who share a common interest in novel solutions for the identification and characterization of proteins from a single cell. The conclusion was that nanomaterials are delivering enhanced reagents and have been tested at the proof-of-concept level, but have yet to be incorporated into routine proteomic workflows.     

High-throughput proteomics using antibody microarrays

Antibody-based microarrays are a novel technology that hold great promise in proteomics. Microarrays can be printed with thousands of recombinant antibodies carrying the desired specificities, the biologic sample (e.g., an entire proteome) and any specifically bound analytes detected. The microarray patterns that are generated can then be converted into proteomic maps, or molecular fingerprints, revealing the composition of the proteome. Using this tool, global proteome analysis and protein expression profiling will thus provide new opportunities for biomarker discovery, drug target identification and disease diagnostics, as well as providing insights into disease biology. Intense work is currently underway to develop this novel technology platform into the high-throughput proteomic tool required by the research community.     

High-throughput proteomics using antibody microarrays

Antibody-based microarrays are a novel technology that hold great promise in proteomics. Microarrays can be printed with thousands of recombinant antibodies carrying the desired specificities, the biologic sample (e.g., an entire proteome) and any specifically bound analytes detected. The microarray patterns that are generated can then be converted into proteomic maps, or molecular fingerprints, revealing the composition of the proteome. Using this tool, global proteome analysis and protein expression profiling will thus provide new opportunities for biomarker discovery, drug target identification and disease diagnostics, as well as providing insights into disease biology. Intense work is currently underway to develop this novel technology platform into the high-throughput proteomic tool required by the research community.     

Urinary proteomics: towards biomarker discovery, diagnostics and prognostics

During recent years, the proteomics field has moved onward to clinical applications, particularly for biomarker discovery, diagnostics and prognostics of human diseases. The urine is one of the ideal clinical samples for such applications because it is readily available in almost all patients, and its collection is very simple and non-invasive. Urinary proteomics thus becomes one of the most interesting subdisciplines in the clinical proteomics area. This article highlights and updates recent progress in the urinary proteomics field for clinical applications.     

Proteomics in clinical trials and practice: present uses and future promise

The study of clinical proteomics is a promising new field that has the potential to have many applications, including the identification of biomarkers and monitoring of disease, especially in the field of oncology. Expression proteomics evaluates the cellular production of proteins encoded by a particular gene and exploits the differential expression and post-translational modifications of proteins between healthy and diseased states. These biomarkers may be applied towards early diagnosis, prognosis, and prediction of response to therapy. Functional proteomics seeks to decipher protein-protein interactions and biochemical pathways involved in disease biology and targeted by newer molecular therapeutics. Advanced spectrometry technologies and new protein array formats have improved these analyses and are now being applied prospectively in clinical trials. Further advancement of proteomics technology could usher in an era of personalized molecular medicine, where diseases are diagnosed at earlier stages and where therapies are more effective because they are tailored to the protein expression of a patient's malignancy.     

Nuclear microenvironments and cancer

Nucleic acids and regulatory proteins are architecturally organized in nuclear microenvironments. The compartmentalization of regulatory machinery for gene expression, replication and repair, is obligatory for fidelity of biological control. Perturbations in the organization, assembly and integration of regulatory machinery have been functionally linked to the onset and progression of tumorigenesis. The combined application of cellular, molecular, biochemical and in vivo genetic approaches, together with structural biology, genomics, proteomics and bioinformatics, will likely lead to new approaches in cancer diagnostics and therapy.     

Mass spectrometry based proteomics and metabolomics in personalized oncology

Precision medicine (PM) means the customization of healthcare with decisions and practices adjusted to the individual patient. It includes personalized diagnostics, patients' sub-classification, individual treatment selection and the monitoring of its effectiveness. Currently, in oncology, PM is based on the molecular and cellular features of a tumor, its microenvironment and the patient's genetics and lifestyle. Surprisingly, the available targeted therapies were found effective only in a subset of patients. An in-depth understanding of tumor biology is crucial to improve their effectiveness and develop new therapeutic targets. Completion of genetic information with proteomics and metabolomics can give broader knowledge about tumor biology which consequently provides novel biomarkers and indicates new therapeutic targets. Recently, metabolomics and proteomics have extensively been applied in the field of oncology. In the context of PM, human studies, with the use of mass spectrometry (MS) which allows the detection of thousands of molecules in a large number of samples, are the most valuable. Such studies, focused on cancer biomarkers discovery or patients' stratification, are presented in this review. Moreover, the technical aspects of MS-based clinical proteomics and metabolomics are described.     

Proteome signatures—how are they obtained and what do they teach us?

The dawn of a new Proteomics era, just over a decade ago, allowed for large-scale protein profiling studies that have been applied in the identification of distinctive molecular cell signatures. Proteomics provides a powerful approach for identifying and studying these multiple molecular markers in a vast array of biological systems, whether focusing on basic biological research, diagnosis, therapeutics, or systems biology. This is a continuously expanding field that relies on the combination of different methodologies and current advances, both technological and analytical, which have led to an explosion of protein signatures and biomarker candidates. But how are these biological markers obtained? And, most importantly, what can we learn from them? Herein, we briefly overview the currently available approaches for obtaining relevant information at the proteome level, while noting the current and future roles of both traditional and modern proteomics. Moreover, we provide some considerations on how the development of powerful and robust bioinformatics tools will greatly benefit high-throughput proteomics. Such strategies are of the utmost importance in the rapidly emerging field of immunoproteomics, which may play a key role in the identification of antigens with diagnostic and/or therapeutic potential and in the development of new vaccines. Finally, we consider the present limitations in the discovery of new signatures and biomarkers and speculate on how such hurdles may be overcome, while also offering a prospect for the next few years in what could be one of the most significant strategies in translational medicine research.     

Analytical nanobiotechnology for medicine diagnostics

The review is concerned with the state-of-the-art and the prospects of development of nanotechnologies in clinical proteomics. Nanotechnology in clinical proteomics is a new medical research direction, dealing with the creation and application of nanodevices for performing proteomic analyses in the clinic. Nanotechnological progress in the field of atomic force microscopy makes it possible to perform clinical studies on the revelation, visualization and identification of protein disease markers, in particular of those with the sensitivity of 10(-17) M that surpasses by several orders the sensitivity of commonly adopted clinical methods. At the same time, implementation of nanotechnological approaches into diagnostics allows for the creation of new diagnostic systems based on the optical, electro-optical, electromechanical and electrochemical nanosensoric elements with high operating speed. The application of nanotechnological approaches to creating nanopore-based devices for express sequencing of the genome is discussed.     

Renal and urinary proteomics: current applications and challenges

During the past few years, proteomics has been extensively applied to various fields of medicine including nephrology. Current applications of renal and urinary proteomics are to better understand renal physiology, to explore the complexity of disease mechanisms, and to identify novel biomarkers and new therapeutic targets. This review provides some examples and perspectives of how proteomics can be applied to nephrology and how experimental data can be linked to physiology, functional significance and clinical applications. In some instances, proteomic analysis can be utilized to generate a new hypothesis from a set of candidates that are obtained from expression studies. The new hypothesis can then be addressed rapidly by conventional molecular biology methods, as demonstrated by identification of an altered renal elastin-elastase system in diabetic nephropathy and alterations in the renal kallikrein-kallistatin pathway in hypoxia-induced hypertension. The strengths and limitations of proteomics in renal research are summarized. Optimization of analytical protocols is required to overcome current limitations. Applications of proteomics to nephrology will then be more fruitful and successful.     

Biomedical applications of protein chips

The development of microchips involving proteins has accelerated within the past few years. Although DNA chip technologies formed the precedent, many different strategies and technologies have been used because proteins are inherently a more complex type of molecule. This review covers the various biomedical applications of protein chips in diagnostics, drug screening and testing, disease monitoring, drug discovery (proteomics), and medical research. The proteomics and drug discovery section is further subdivided to cover drug discovery tools (on-chip separations, expression profiling, and antibody arrays), molecular interactions and signaling pathways, the identification of protein function, and the identification of novel therapeutic compounds. Although largely focused on protein chips, this review includes chips involving cells and tissues as a logical extension of the type of data that can be generated from these microchips.     

Effects of preanalytical variables on peptide and protein measurements in human serum and plasma: implications for clinical proteomics

There is a wealth of knowledge in the field of in vitro diagnostics with regard to preanalytical variables and their impact on the determination of peptide and protein analytes in human serum and plasma. This information is applicable to clinical proteomics investigations, which utilize the same sample types. Studies have demonstrated that the majority of variations and errors in in vitro diagnostics seem to occur in the preanalytical phase prior to specimen analysis. Preanalytical processes include study design, compliance of the subjects investigated, compliance of the technical staff in adherence to protocols, choice of specimens utilized and sample collection and processing. These variables can have a dramatic impact on the determination of analytes and can affect result outcomes, reproducibility and the validity of investigations. By drawing analogies to in vitro diagnostics practices, specific variables that are likely to impact the results of proteomics studies can be identified. Recognition of such variables is the first step towards their understanding and, eventually, controlling their impact. In this article, we will review preanalytical variables, provide examples for their effects on the determination of distinct peptides and proteins and discuss potential implications for clinical proteomics investigations.     

The methods of quantitative proteomics

In modern science proteomic analysis is inseparable from other fields of systemic biology. Possessing huge resources quantitative proteomics operates colossal information on molecular mechanisms of life. Advances in proteomics help researchers to solve complex problems of cell signaling, posttranslational modification, structure and funciotnal homology of proteins, molecular diagnostics etc. More than 40 various methods have been developed in proteomics for quantitative analysis of proteins. Although each method is unique and has certain advantages and disadvantages all these use various isotope labels (tags). In this review we will consider the most popular and effective methods employing both chemical modifications of proteins and also metabolic and enzymatic methods of isotope labeling.     

Application of proteomics to ecology and population biology

Proteomics is a relatively new scientific discipline that merges protein biochemistry, genome biology and bioinformatics to determine the spatial and temporal expression of proteins in cells, tissues and whole organisms. There has been very little application of proteomics to the fields of behavioral genetics, evolution, ecology and population dynamics, and has only recently been effectively applied to the closely allied fields of molecular evolution and genetics. However, there exists considerable potential for proteomics to impact in areas related to functional ecology; this review will introduce the general concepts and methodologies that define the field of proteomics and compare and contrast the advantages and disadvantages with other methods. Examples of how proteomics can aid, complement and indeed extend the study of functional ecology will be discussed including the main tool of ecological studies, population genetics with an emphasis on metapopulation structure analysis. Because proteomic analyses provide a direct measure of gene expression, it obviates some of the limitations associated with other genomic approaches, such as microarray and EST analyses. Likewise, in conjunction with associated bioinformatics and molecular evolutionary tools, proteomics can provide the foundation of a systems-level integration approach that can enhance ecological studies. It can be envisioned that proteomics will provide important new information on issues specific to metapopulation biology and adaptive processes in nature. A specific example of the application of proteomics to sperm ageing is provided to illustrate the potential utility of the approach.     

差异蛋白质组学的研究进展

差异蛋白质组是蛋白质组学研究的一个主要内容,其核心在于寻找某种特定臣寸素引起样本之间蛋白质组的差异,揭示并验证蛋白质组在生理或病理过程中的变化。进一步对蛋白质组差异信息分析后,理论上可以推断造成这种变化的原因。因此,对于临床上肿瘤预诊、药物靶标寻找、细胞调控分子的鉴别等有着极大的实际意义。差异蛋白质组研究要求可靠性和可重复性。因此,对于样本处理要求较高,激光微切割技术和高丰度蛋白去除技术的应用优化了样本处理方法。目前差异蛋白质组的主要研究方法仍是2-DE分离和MS鉴定联合应用,基于2-DE的2-DDIGE方法弥补了2-DE的弱点,更适用于差异蛋白质组研究。除2-DE技术外的其他几种技术手段,如多维液相色谱分离技术、ICAT技术、蛋白芯片技术等差异蛋白质组学研究技术可以作为2-DE技术的补充,甚至或替代技术。     

Proteomics of Staphylococcus aureus--current state and future challenges

This paper presents a short review of the proteome of Staphylococcus aureus, a gram-positive human pathogen of increasing importance for human health as a result of the increasing antibiotic resistance. A proteome reference map is shown which can be used for future studies and is followed by a demonstration of how proteomics could be applied to obtain new information on S. aureus physiology. The proteomic approach can provide new data on the regulation of metabolism as well as of the stress or starvation responses. Proteomic signatures encompassing specific stress or starvation proteins are excellent tools to predict the physiological state of a cell population. Furthermore proteomics is very useful for analysing the size and function of known and unknown regulons and will open a new dimension in the comprehensive understanding of regulatory networks in pathogenicity. Finally, some fields of application of S. aureus proteomics are discussed, including proteomics and strain evaluation, the role of proteomics for analysis of antibiotic resistance or for discovering new targets and diagnostics tools. The review also shows that the post-genome era of S. aureus which began in 2001 with the publication of the genome sequence is still in a preliminary stage, however, the consequent application of proteomics in combination with DNA array techniques and supported by bioinformatics will provide a comprehensive picture on cell physiology and pathogenicity in the near future.     

Proteomics approach and techniques in identification of reliable biomarkers for diseases

Biomarkers, also called biological markers, are indicators to identify a biological case or situation as well as detecting any presence of biological activities and processes. Proteins are considered as a type of biomarkers based on their characteristics. Therefore, proteomics approach is one of the most promising approaches in this field. The purpose of this review is to summarize the use of proteomics approach and techniques to identify proteins as biomarkers for different diseases. This review was obtained by searching in a computerized database. So, different researches and studies that used proteomics approach to identify different biomarkers for different diseases were reviewed. Also, techniques of proteomics that are used to identify proteins as biomarkers were collected. Techniques and methods of proteomics approach are used for the identification of proteins' activities and presence as biomarkers for different types of diseases from different types of samples. There are three essential steps of this approach including: extraction and separation of proteins, identification of proteins, and verification of proteins. Finally, clinical trials for new discovered biomarker or undefined biomarker would be on.     

Defining the mandate of proteomics in the post-genomics era: workshop report

Research in proteomics is the next step after genomics in understanding life processes at the molecular level. In the largest sense proteomics encompasses knowledge of the structure, function and expression of all proteins in the biochemical or biological contexts of all organisms. Since that is an impossible goal to achieve, at least in our lifetimes, it is appropriate to set more realistic, achievable goals for the field. Up to now, primarily for reasons of feasibility, scientists have tended to concentrate on accumulating information about the nature of proteins and their absolute and relative levels of expression in cells (the primary tools for this have been 2D gel electrophoresis and mass spectrometry). Although these data have been useful and will continue to be so, the information inherent in the broader definition of proteomics must also be obtained if the true promise of the growing field is to be realized. Acquiring this knowledge is the challenge for researchers in proteomics and the means to support these endeavors need to be provided. An attempt has been made to present the major issues confronting the field of proteomics and two clear messages come through in this report. The first is that the mandate of proteomics is and should be much broader than is frequently recognized. The second is that proteomics is much more complicated than sequencing genomes. This will require new technologies but it is highly likely that many of these will be developed. Looking back 10 to 20 years from now, the question is: Will we have done the job wisely or wastefully? This report summarizes the presentations made at a symposium at the National Academy of Sciences on February 25, 2002.