Post-genomic World Research Articles

The new genetic medicine: theological and ethical reflections

Chapter 1 Theological Issues in Genetics Chapter 2 thical Issues in Genetics Chapter 3 Catholic Reflections on the Human Genome Project Chapter 4 Reflections on the Moral Status of the Pre-embryo Chapter 5 Human Nature in a Post-Genomic World Chapter 6 Human Gene Transfer: Some Theological Contributions to the Ethi-cal Debate Chapter 7 Human Cloning: Religious and Ethical Issues Chapter 8 Human Embryonic Stem Cell Therapy Chapter 9 Ethical Issues in Stem Cell Therapy: From the Micro to the Macro Chapter 10 The Bioengineering of Planet Earth: Some Scientific, Moral and Theological Considerations

A general approach to detect protein expression in vivo using fluorescent puromycin conjugates.

Understanding the expression of known and unknown gene products represents one of the key challenges in the post-genomic world. Here, we have developed a new class of reagents to examine protein expression in vivo that does not require transfection, radiolabeling, or the prior choice of a candidate gene. To do this, we constructed a series of puromycin conjugates bearing various fluorescent and biotin moieties. These compounds are readily incorporated into expressed protein products in cell lysates in vitro and efficiently cross cell membranes to function in protein synthesis in vivo as indicated by flow cytometry, selective enrichment studies, and Western analysis. Overall, this work demonstrates that fluorescent-puromycin conjugates offer a general means to examine protein expression in vivo.

The planetary biology of cytochrome P450 aromatases

BackgroundJoining a model for the molecular evolution of a protein family to the paleontological and geological records (geobiology), and then to the chemical structures of substrates, products, and protein folds, is emerging as a broad strategy for generating hypotheses concerning function in a post-genomic world. This strategy expands systems biology to a planetary context, necessary for a notion of fitness to underlie (as it must) any discussion of function within a biomolecular system.ResultsHere, we report an example of such an expansion, where tools from planetary biology were used to analyze three genes from the pig Sus scrofa that encode cytochrome P450 aromatases–enzymes that convert androgens into estrogens. The evolutionary history of the vertebrate aromatase gene family was reconstructed. Transition redundant exchange silent substitution metrics were used to interpolate dates for the divergence of family members, the paleontological record was consulted to identify changes in physiology that correlated in time with the change in molecular behavior, and new aromatase sequences from peccary were obtained. Metrics that detect changing function in proteins were then applied, including KA/KS values and those that exploit structural biology. These identified specific amino acid replacements that were associated with changing substrate and product specificity during the time of presumed adaptive change. The combined analysis suggests that aromatase paralogs arose in pigs as a result of selection for Suoidea with larger litters than their ancestors, and permitted the Suoidea to survive the global climatic trauma that began in the Eocene.ConclusionsThis combination of bioinformatics analysis, molecular evolution, paleontology, cladistics, global climatology, structural biology, and organic chemistry serves as a paradigm in planetary biology. As the geological, paleontological, and genomic records improve, this approach should become widely useful to make systems biology statements about high-level function for biomolecular systems.

Chemical communication in a post-genomic world.

With genome sequences accumulating at a rapid pace, one major goal of biology is to understand the function of genes. Many gene functions are comprehensible only within the context of chemical communication, and emerging research on genomics and chemical communication has catalyzed development of this highly productive interface. Many of the most abundantly represented genes in the genomes characterized to date encode proteins mediating interactions among organisms, including odorant receptors and binding proteins, enzymes involved in biosynthesis of pheromones and toxins, and enzymes catalyzing the detoxification of defense compounds. Chemosensory signaling shares several features irrespective of taxon; components of the vast majority of chemosensory signaling systems include a receptor that interacts with a signal molecule, a …

Understanding the chemistry of chemical communication: are we there yet?

Small molecules often carry vital information. Compounds as simple as nitric oxide, carbon dioxide, and ethylene play essential roles as hormones or pheromones in plants and animals. Extensive research during the past century has revealed that chemical signaling is not only the primary means whereby organisms coordinate and regulate their internal activities, but also the chief channel through which organisms interact with one another. In this Introduction, I will examine briefly the evolution of the science of organic chemistry, which lies at the heart of chemical communication, and consider what some future goals for organic chemistry in a postgenomic world may be. By the start of the 19th century, chemists had begun to make sense of the inorganic world. Elements were being discovered at a rapid rate, and the importance of quantitative research had become apparent. Chemists' curiosity naturally extended to the study of compounds making up living organisms as well, but ”organic” chemistry, the chemical study of the biotic world, presented essentially insurmountable difficulties. In the preface to his pioneering treatise, Lectures on Animal Chemistry (1806), J. J. Berzelius wrote ”... Of all of the sciences contributing to medicine, chemistry is the primary one, and apart from the general light it throws on the entire art of healing, it will soon bestow on some of its branches a perfection such as one never could have anticipated.” Despite this exuberance, worthy of the introductory section of any contemporary chemist's National Institutes of Health research grant application, it was only 4 years later that Berzelius himself became deeply discouraged with the unreliability of his own analytical work on animal products, declaring in 1810 that he had written his last paper on nasal mucus, bile, urine, and related subjects (1). Although by 1831 Justus Liebig was able to report elemental analyses of …

Use of gene therapy in central nervous system repair.

Recent advances have increased our molecular understanding of the central nervous system (CNS), in both health and disease. In order to realize the clinical benefits of these findings, new molecular-based therapies need to be developed, such as CNS gene therapy. Although the field has suffered setbacks, it remains an attractive technology for providing new therapies in the post-genomic world. The development of new vectors, and their extensive application in animal models of CNS disease, provides evidence suggesting that gene therapy will eventually become an accepted clinical option. In fact, the first gene therapy clinical trial for Parkinson's disease has recently begun. This review discusses how gene therapy has been applied in animal models, and how it may be used to repair the damage caused by CNS diseases and trauma in human beings. Furthermore, it explores how such treatments may be combined with, and augment, more conventional therapeutic approaches.

Richard Weinshilboum: Pharmacogenetics: The future is here!

Richard Weinshilboum has a no-nonsense attitude about pharmacogenetics. He is enthusiastic about the practicalities and ramifications of the field's solid accomplishments, but he carefully measures statements that might feed the hype that is en courant about the brave new postgenomic world of drug therapy. Although the terms "pharmacogenomics" and "pharmacogenetics" are often used interchangeably (a linguistic quirk to which Weinshilboum does not object), he consistently avoids the latter, perhaps more glitzy, word. Weinshilboum has spent over thirty years as a clinical pharmacologist, exploring in particular the variability of drug metabolism that occurs among patients as a function of their genetic constitution. The research efforts from his line of work have materialized into clinical application and have helped to set the stage for the individualization of drug treatment according to each patient's genetic constitution-not yet on the genomewide scale that Weinshilboum enthusiastically foresees, but certainly as pertains to multiple genes and drugs for any given patient. The interview with Weinshilboum occurred at this year's annual meeting of ASPET, at which he was conferred the Harry Gold Award in Clinical Pharmacology.

Bioinformatics in a post-genomics world--the need for an inclusive approach.

Bioinformatics in a post-genomics world--the need for an inclusive approach.

Mixed signals in heart failure: cancer rules.

cancer: a disease marked by tumor-like growth —Merriam-Webster’s Ninth Collegiate Dictionary In the world according to Webster, heart failure is a form of cardiac cancer. Although primary cardiac malignancies are among the most rare of human diseases, this singular viewpoint is substantiated by the massive, abnormal, “tumor-like” growth in cardiac muscle that accompanies heart failure. The biological principles of cell growth, death, and survival are as important in the onset of heart failure as in tumor progression, and the molecular signals for cell proliferation and cardiac myocyte hypertrophy are highly conserved. Both diseases are inexorable and progressive, characterized by clinical stages that predict survival and outcome, ultimately resulting in a terminal phase. There are “multi-hit” pathways for both cancer and heart failure progression, largely based upon the interplay between genetic susceptibility and environmental stimuli. Like cancer, heart failure represents one of the most important unmet clinical needs in medicine today. Heart failure remains poorly understood and is largely treated symptomatically by a complex regimen of drugs whose actions we are neither entirely sure of nor comfortable with. The lack of new biologically targeted therapy reflects the combined result of the prohibitive cost of large-scale survival trials of adjunctive therapy designed to incrementally slow heart failure progression, and the lack of clear clinical and/or molecular surrogates that have predictive value. In short, the pipeline of heart failure drugs is running dry. Perhaps the time has come to attempt to dissect the mixed signals for heart failure from the viewpoint of recent advances in cancer biology. On a molecular level, the failing heart represents the end result of multiple cues for the growth, death, and survival of cardiac myocytes, many of which are shared with signaling pathways in cancer biology (1, 2). In the failing heart, the underlying disease is also driven by multiple positive and negative signaling pathways, but these are connected to specific phenotypic endpoints that are more physiologically complex, e.g., electrical conduction, contractility, relaxation, mechanical activation, and chamber morphogenesis (Figure ​(Figure1).1). The development of new, biologically targeted therapies for cancer has been fostered by placing therapy into the framework of fundamental pathways that control the cell cycle and subsequent tumor cell proliferation. In a similar manner, understanding the molecular logic of heart failure will ultimately require forming mechanistic connections between defined clinical disease surrogates with specific positive and negative molecular checkpoints that arise at specific stages during the natural temporal progression of this chronic disease. In the current post-genome world, a new wave of work in heart failure has begun to attack the integrative biology of heart failure at multiple levels: genomic, genetic, and physiological in creatures great and small (3). This brief review will highlight recent progress in the field and point out new directions for research into this disease process. Figure 1 Mechanical stress–induced transmembrane signaling and integrated phenotypes of failing heart. The activation profiles of various signaling cascades and time-dependent changes in phenotypic features of heart failure are illustrated based on our ... Note. Interested readers are referred to the supplemental reading list (www.jci.org/cgi/content/full/109/7/849/DC1) for detailed references to the data presented in the tables and figures.

Grain of truth.

Grain of truth.

Evaluation of childhood sensorineural hearing loss in the post-genome world.

Evaluation of childhood sensorineural hearing loss in the post-genome world.

The Role of IRBs in Research Involving Commerical Biobanks

In the post-genome world of biomedical research, an increasingly common research strategy is to focus on large repositories of biological specimens. There are now several well-known efforts to compile vast collections of biological materials, reanalyze extant samples, collect new ones, and link the samples to medical records. The significant issues of law, ethics, and policy raised by these research activities usually are heightened when commercial enterprises play a leading role in accumulating and distributing the samples. Emerging companies are not only compiling repositories for their own use, but some companies are positioning themselves to act as intermediaries, developing vast biobanks for sale to a wide range of other researchers.

Challenges for neuroscience in a post-genome world.

Challenges for neuroscience in a post-genome world.

High-throughput proteomics: protein expression and purification in the postgenomic world.

Proteomics has become a major focus as researchers attempt to understand the vast amount of genomic information. Protein complexity makes identifying and understanding gene function inherently difficult. The challenge of studying proteins in a global way is driving the development of new technologies for systematic and comprehensive analysis of protein structure and function. Protein expression and purification are key processes in these studies, but have typically only been applied on a case-by-case basis to proteins of interest. Researchers are addressing the challenge of parallel expression and purification of large numbers of gene products through the principles of high-throughput screening technologies commonly used in pharmaceutical development. Some of the issues relevant to these approaches are discussed here.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

DISCOVERY at the boundaries of the post-genomics world.

Post-genomic science: converting primary structure into physiological function.

Abstract Exobiology, the study of the origin, evolution and distribution of life (including life on earth) within the context of cosmic evolution, is being given a remarkable boost by genome sequencing projects, which are now making the evolutionary histories of protein families routinely available. These histories comprise a multiple alignment for their protein sequences and the corresponding DNA sequences, an evolutionary tree showing the pedigree of these sequences, and reconstructed ancestral sequences for each node in the tree. In a post-genomic world having genomic sequences from an unlimited number of organisms, these histories will be used to connect structure, chemical reactivity, and physiological function to these families. This paper describes several “post-genomic” tools that exploit these evolutionary histories. They can be used to confirm or deny long distance homology between two protein families, identify proteins within a family that have new functions, and identify specific in vitro properties of the protein that are important for its physiological role. Evolution-based data structures for organizing large sequence databases are also described.

The national cancer institute (NCI) and cancer biology in a “post genome world”

The national cancer institute (NCI) and cancer biology in a “post genome world”