Reframing epigenetics: three dimensions in the post-genomic era

In our Dalton Transactions Perspective article entitled, 'Metal-based antitumour drugs in the post genomic era', (Dalton Trans., 2006, 1929-1933) we discussed metal-based drugs in light of past decades of research. We concluded that the post-genomic era would dictate a change in the direction of the field with knowledge of the genome increasingly allowing protein targets to be identified and not simply assuming that DNA is the only relevant target of metal-based drugs. Since our article was published new insights into the mode of action of metal-based drugs have emerged making some older findings increasingly relevant to current drug design. In this article we discuss these developments in terms of what we believe should be the future direction for the field.

Post genomic era is known for the explosive growth in biomedical information. Bibliographic and sequence databases are increasing continuously and have voluminous data sets. Biomedical librarians are facing challenges in retrieval of relevant information from these electronic databases and related sources of information. This chapter discusses the changing role of biomedical librarians in post genomic era. The chapter covers features of the biomedical librarianship including library collection development, users' information needs and strategies adopted to provide services. Moreover, it focuses on the competencies required by librarians to face the challenges of management of information and services needed by biomedical researchers in the post genomic era.

The VH domains of two human monoclonal antibodies, designated Mcg IgG1(lambda) and Yvo IgM(kappa), were particularly intractable to standard protein sequencing protocols. Peptides liberated from the VH domains of these proteins, using standard enzymatic or chemical cleavages, invariably precipitated during the procedures. Boiling in SDS containing buffers dissolved precipitates and the peptides were separated using SDS-PAGE. Fully overlapped VH sequences were obtained with a series of 'in-gel' cleavages, followed by passive/differential transfers of peptides onto PVDF membranes. Both the in-gel cleavages and passive transfers could be applied to 'wet' or 'dry' gels so that gels could be archived and used at a later date to obtain additional sequence information from a fragment of interest. Repetitive yields of even the most insoluble peptides were such that the sequences of various peptides from relatively complex mixtures of peptides could be assigned with confidence. Despite the overall success of the sequencing, we occasionally referred to electron density maps, calculated for crystals of the Fab of Yvo IgM, to resolve particular sequences and confirm ambiguous amino acid assignments. Methods we describe in this report should be generally useful for obtaining sequences of proteins with intractable cores and may find many applications in the 'post genomic era'.

Post genomic era is known for the explosive growth in biomedical information. Bibliographic and sequence databases are increasing continuously and have voluminous data sets. Biomedical librarians are facing challenges in retrieval of relevant information from these electronic databases and related sources of information. This chapter discusses the changing role of biomedical librarians in post genomic era. The chapter covers features of the biomedical librarianship including library collection development, users' information needs and strategies adopted to provide services. Moreover, it focuses on the competencies required by librarians to face the challenges of management of information and services needed by biomedical researchers in the post genomic era.

Artificial protein-RNA hybrid ribozymes with an unwinding activity were created. Since the novel hybrid ribozymes can attack any site within mRNA, libraries can be made of the hybrid ribozymes with randomized binding arms and thus be introduced into cells. This represents a new paradigm of powerful ribozyme technology that can enjoy many unique and exciting uses for various purposes in the post-genome project era, including applications for discovery of novel functional genes associated with specific important phenotypes and targeted elimination of expression of disease-causing genes in vivo in gene therapy approaches.

The history of modernity is a story about humans emancipating themselves from prejudice and superstition through reason and science. Scientific research has been a major driving force of progress for human civilization since the industrial revolution in the mid‐18th century. During the past 250 years, humans have rapidly increased their use of science, as a tool not only to understand and shape their environment, but also to improve themselves with better health care and longer, more comfortable lives. Unfortunately, the application of science has not always been appropriate: Darwin's theory of natural selection was applied to social policies in the form of eugenics from the early 19th century until the second half of the 20th century. In this period, eugenics remained a popular ideology and, as a consequence, genetics was a popular science. It was also a period of significant human migration that increased racial diversity in Western nations, with resulting concerns about racial purity. Naturalism and social Darwinism were very popular throughout, while industrialization led to massive urbanization and increasing pauperism. Politically, it was a time of interventionist policies, such as the so‐called Progressive Era in the USA that led to drastic social and political change. > No more divine designer, no more life force is needed; life is determined by a genetic program and evolves as a result of chance—or human choice—and selection Eugenics gained scientific legitimacy in the early 20th century owing to Mendelian genetics, which offered a rational, scientific theory to understand, predict, and control heredity and thereby the characteristics of future generations. As pauperism, criminality, and “feeblemindedness” were thought to be genetically determined, eugenics offered a tool to eliminate these undesirable traits from the human population. Of course, the idea of a single and universal definition of “the gene” is currently disappearing together …

Plants are a valuable source of pharmacologically important compounds since these are traditionally important in medicinal systems. Medicinal plant-based ancient wisdom could serve as a powerful tool to facilitate focused research on natural compounds for the drug discovery process. Medicinal plants are more important sources for drug discovery, specifically lead molecules as these offer several advantages over the synthetic molecules. Since in post genomic era, molecular targets for most diseases are known, conventional bioscreening strategies for medicinal plants are not sufficient to fulfill the present demand. It makes the role of medicinal plants more significant than ever before. The rich heritage of Indian medicinal plants can be explored utilizing various computational approaches for bioprospecting in the post-genomic era. In this review, the authors explore how Indian medicinal plant legacy can be utilized in post-genomic era utilizing the computational, bioinformatics, chemo-informatics, genomics and systems biology approaches. This approach shall make possible the systematic analysis integrating traditional and modern data in order to validate medicinal plant based knowledge.

The post genomic era has promised major breakthroughs in personalized medicine which will improve a patient's health by selecting treatments including diet based on the patient's unique DNA sequence. The post genomic era is allowing scientists and clinicians to examine an individuals' DNA and then recommend the best diet in order to remain healthy and attenuate disease processes which the individual might be predisposed to because of their genetic make-up, e.g., cardiovascular disease. Nutrigenomics and nutrigenetics are related terms to pharmacogenomics and pharmacogenetics with an emphasis on diet or nutrition. There has been an increasing interest in consumers on natural medicines or Nutraceuticals in order to remain healthy. The post genomic era will allow a patient to visit their physician who will screen the patients DNA on a silicon chip. This will indicate which of the patient's genes have polymorphisms, e.g., a single nucleotide polymorphism (SNP) that might lead the patient to be more susceptible to certain diseases and then the physician could prescribe the appropriate dietary supplements to prevent or diminish these potential diseases. Several recently published patents are discussed in the article covering recent developments in the field.

One of the biggest surprises at the beginning of the 'post-genome era' was the discovery of numerous genes encoding microRNAs. They were found in genomes of such diverse organisms as Caenorhabditis elegans, Drosophila melanogaster, Arabidopsis thaliana, and Homo sapiens which implies their important role in multicellular life evolution. The number of microRNA genes is estimated to be nearly 1% of that of protein-coding genes. Their products, tiny RNAs, are thought to regulate gene expression during development, organogenesis, and very likely during many other processes, by hybridizing to their target mRNAs. The cellular functions of mRNAs that are regulated by microRNAs are only beginning to be revealed, and details of this regulation mechanism are still poorly understood. In this article we discuss the possible mechanisms of microRNA biogenesis with special emphasis on their structural aspects. We have focused on the factors and effects that may be responsible for the existing length differences between different microRNAs, and for the observed length heterogeneity within some individual microRNA species.

Implications for medicine in the ‘post-genomic era’

The c-Myc oncoprotein is a master regulator of genes involved in diverse cellular processes. Situated upstream of signalling pathways regulating cellular replication/growth as well as apoptosis/growth arrest, c-Myc may help integrate processes determining cell numbers and tissue size in physiology and disease. In cancer, this 'dual potential' allows c-Myc to act as its own tumour suppressor. Evidently, given that deregulated expression of c-Myc is present in most, if not all, human cancers (Table 1) and is associated with a poor prognosis, by implication these in-built 'failsafe' mechanisms have been overcome. To explore the complex activity of c-Myc and its potential as a therapeutic target 'post-genome era' technologies for determining global gene expression alongside advanced new models for the study of tumourigenesis in vivo have proved invaluable. Thus, many recent studies have provided encouragement for the therapeutic targeting of c-Myc in cancer and have revealed new protein targets for manipulating aspects of c-Myc activity. The remarkable regression of even advanced and genetically unstable tumours, seen following deactivation of c-Myc in various models is particularly exciting. This review will discuss what is known about the role of c-Myc in growth deregulation and cancer and will conclude with a discussion of the most promising recent developments in Myc-targeted therapeutics.

In the 'postgenome era', most research on the neuroendocrine control of energy homeostasis has focused on hormonal and neuropeptide control of food intake (i.e. the amount of food eaten) in rats and mice. The amount of food consumed is influenced by both the motivation to procure food and the consummatory act of ingestion. In some species, the rate of food intake remains relatively constant, while survival is maintained via changes in food procurement, external storage and internal expenditure. For example, in hamsters, metabolic signals, peripheral hormones and central neuropeptides influence hunger motivation, food hoarding and changes in energy expenditure without necessarily influencing the amount of food ingested. A similar suite of metabolic signals, hormones and neuropeptides is involved in optimizing reproductive success under fluctuating energetic conditions. Reproductive processes are inhibited or delayed when energy expenditure outstrips energy intake and mobilization from storage. Estrous cyclicity in Syrian hamsters is sensitive to the availability of oxidizable glucose, but the presence of central glucose alone is not sufficient for normal estrous cycles. Food deprivation-induced anestrus does not depend upon food deprivation-induced increases in concentrations of adrenal hormones such as glucocorticoids. If hormones such as insulin and leptin play a role, they might do so by modulating the availability of glucose detected at extra-hypothalamic sites, instead of or in addition to direct effects on the mechanisms that control gonadotropin releasing hormone secretion. Despite our ability to measure and manipulate gene transcription, understanding of fuel homeostasis requires examination of indirect effects of hormones and neuropeptides on peripheral metabolism, attention to the motivational as well as consummatory aspects of ingestion, and the study of behaviour in a natural or seminatural context.

Oligonucleotide microarray has been one of the most powerful tools in the 'Post-Genome Era' for its high sensitivity, high throughput and parallel processing capability. To achieve high detection specificity, we fabricated an isothermal microarray using locked nucleic acid (LNA)-modified oligonucleotide probes, since LNA has demonstrated the advanced ability to enhance the binding affinity toward their complementary nucleotides. After designing the nucleotide sequences of these oligonucleotide probes for gram-positive bacilli of similar origin (Bacillus subtilis, Bacillus licheniformis, Bacillus pumilus, Bacillus megaterium and Bacillus circulans), we unified the melting temperatures of these oligonucleotide probes by modifying some nucleotides using LNA. Furthermore, we optimized the experimental procedures of hydrating microarray slides, blocking side surface as well as labelling the PCR products. Experimental results revealed that KOD Dash DNA polymerase could efficiently incorporate Cy3-dCTP into the PCR products, and the LNA-isothermal oligonucleotide microarray were able to distinguish the bacilli of similar origin with a high degree of accuracy and specificity under the optimized experimental condition.

The role of the toxicologic pathologist in the post-genomic era(#).

One of the most tantalising 'grand challenges' in structural biology is to solve the problem of predicting the structure of a protein from its amino acid sequence alone. Although this problem appeals to many researchers on a purely academic level, the practical importance of protein structure prediction has become particularly clear with the release of the first draft of the complete human genome sequence last year. This moved modern biology into the new so-called 'post genome' era, and for the foreseeable future, one of the main issues in modern biology will be the characterisation of the many 'unknown' gene sequences which are now sitting waiting in DNA and protein data banks. Protein structure can provide a great deal of insight into the evolutionary origins, function and mechanism of a protein, and so any means for determining the 3-D structure of a novel protein will likely be of critical importance.