From bench to briefs

Patent law offers opportunities for those who wish to leave the lab but not science.     

Biological networks 101: Computational modeling for molecular biologists

Computational modeling of biological networks permits the comprehensive analysis of cells and tissues to define molecular phenotypes and novel hypotheses. Although a large number of software tools have been developed, the versatility of these tools is limited by mathematical complexities that prevent their broad adoption and effective use by molecular biologists. This study clarifies the basic aspects of molecular modeling, how to convert data into useful input, as well as the number of time points and molecular parameters that should be considered for molecular regulatory models with both explanatory and predictive potential. We illustrate the necessary experimental preconditions for converting data into a computational model of network dynamics. This model requires neither a thorough background in mathematics nor precise data on intracellular concentrations, binding affinities or reaction kinetics. Finally, we show how an interactive model of crosstalk between signal transduction pathways in primary human articular chondrocytes allows insight into processes that regulate gene expression.     

Hypercard-based data management tools for molecular biologists

I have designed a Macintosh data management system for molecularbiologists. This system, called DataMinder, can be used to storeinformation about oligonucleotides, nucleic acid or proteinsequences, recombinant DNA clones, cells, reagents and protocols.DataMinder is not limited to data storage. A number of utilitiesfor data analysis are provided, including those for the evaluationof oligonucleotides for use as hybridization probes or primersfor DNA synthesis, and a variety of sequence editing features.Context-sensitive help is available on-line. DataMinder is simpleto use and to customize and allows for sharing of database informationacross a computer network.     

Mesenchymal stem cells: From bench to bedside

Human mesenchymal stem cells (hMSCs) have tremendous promise for use in a variety of clinical applications. The ability of these cells to self-renew and differentiate into multiple tissues makes them an attractive cell source for a new generation of cell-based regenerative therapies. Encouraging results from clinical trials have also generated growing enthusiasm regarding MSC therapy and related treatment, but gaps remain in understanding MSC tissue repair mechanisms and in clinical strategies for efficient cell delivery and consistent therapeutic outcomes. For these reasons, discoveries from basic research and their implementation in clinical trials are essential to advance MSC therapy from the laboratory bench to the patient's bedside.     

Vaccinia virus: a versatile tool for molecular biologists.

Continued advances in genetic engineering have made possible the high-level expression of correctly processed cellular, viral and bacterial polypeptides. This article focuses on viral expression vectors and, more specifically, the vaccinia virus expression system. Vaccinia virus has been used to express a variety of proteins with useful immunogenic, catalytic or pharmaceutical properties. We discuss briefly the biology of vaccinia and its significance in the use of vaccinia as an expression vector, the variety of vaccinia systems currently in use and, finally, we summarize some recent developments which bode well for future applications of vaccinia virus technology.     

From bench to bedside: stealth of enteroinvasive pathogens

Bacterial enteric infections are often associated with diarrhoea or vomiting, which are clinical presentations commonly referred to as gastroenteritis. However, some enteric pathogens, including typhoidal Salmonella serotypes, Brucella species and enteropathogenic Yersinia species are associated with a clinical syndrome that is characterized by abdominal pain and/or fever and is distinct from acute gastroenteritis. Recent insights into molecular mechanisms of the host-pathogen interaction show that these enteric pathogens share important characteristics that explain why the initial host responses associated with these agents more closely resemble host responses to viral or parasitic infections. Host responses contribute to the clinical presentation of disease and improved understanding of these responses in the laboratory is beginning to bridge the gap between bench and bedside.     

From bedside to bench to clinic trials: identifying new treatments for severe asthma

Asthmatics with a severe form of the disease are frequently refractory to standard medications such as inhaled corticosteroids, underlining the need for new treatments to prevent the occurrence of potentially life-threatening episodes. A major obstacle in the development of new treatments for severe asthma is the heterogeneous pathogenesis of the disease, which involves multiple mechanisms and cell types. Furthermore, new therapies might need to be targeted to subgroups of patients whose disease pathogenesis is mediated by a specific pathway. One approach to solving the challenge of developing new treatments for severe asthma is to use experimental mouse models of asthma to address clinically relevant questions regarding disease pathogenesis. The mechanistic insights gained from mouse studies can be translated back to the clinic as potential treatment approaches that require evaluation in clinical trials to validate their effectiveness and safety in human subjects. Here, we will review how mouse models have advanced our understanding of severe asthma pathogenesis. Mouse studies have helped us to uncover the underlying inflammatory mechanisms (mediated by multiple immune cell types that produce Th1, Th2 or Th17 cytokines) and non-inflammatory pathways, in addition to shedding light on asthma that is associated with obesity or steroid unresponsiveness. We propose that the strategy of using mouse models to address clinically relevant questions remains an attractive and productive research approach for identifying mechanistic pathways that can be developed into novel treatments for severe asthma.     

Useful Microsoft Word Macros for molecular biologists and protein chemists

Biologists today make extensive use of word processing programs for the production of research reports, literature reviews and grant proposals. Frequently, such programs become the default platform for viewing and the later publication of protein and nucleic acid sequence data. Thus, researchers often switch between their word processor and more specialized programs designed to analyze protein and nucleic acid sequences. It would be more convenient to perform these simple sequence analyses using the word processor without switching to another program. The focus here is on the use of the Visual Basic programming language, which is built into all recent versions of Microsoft Word to generate surprisingly complex and useful macros that can conveniently analyze several important features of protein and nucleic acid sequences. The standard Word interface can also be easily modified to display and run these macros from a pull-down menu. Several examples of this approach are provided.     

Wild type p53 reactivation: From lab bench to clinic

The p53 tumor suppressor is the most frequently inactivated gene in cancer. Several mouse models have demonstrated that the reconstitution of the p53 function suppresses the growth of established tumors. These facts, taken together, promote the idea of p53 reactivation as a strategy to combat cancer. This review will focus on recent advances in the development of small molecules which restore the function of wild type p53 by blocking its inhibitors Mdm2 and MdmX or their upstream regulators and discuss the impact of different p53 functions for tumor prevention and tumor eradication. Finally, the recent progress in p53 research will be analyzed concerning the role of p53 cofactors and cellular environment in the biological response upon p53 reactivation and how this can be applied in clinic.     

Inosine and hypoxanthine as novel biomarkers for cardiac ischemia: From bench to point-of-care

Cardiac ischemia associated with acute coronary syndrome and myocardial infarction is a leading cause of mortality and morbidity in the world. A rapid detection of the ischemic events is critically important for achieving timely diagnosis, treatment and improving the patient''s survival and functional recovery. This minireview provides an overview on the current biomarker research for detection of acute cardiac ischemia. We primarily focus on inosine and hypoxanthine, two by-products of ATP catabolism. Based on our published findings of elevated plasma concentrations of inosine/hypoxanthine in animal laboratory and clinical settings, since 2006 we have originally proposed that these two purine molecules can be used as rapid and sensitive biomarkers for acute cardiac ischemia at its very early onset (within 15 min), hours prior to the release of heart tissue necrosis biomarkers such as cardiac troponins. We further developed a chemiluminescence technology, one of the most affordable and sensitive analytical techniques, and we were able to reproducibly quantify and differentiate total hypoxanthine concentrations in the plasma samples from healthy individuals versus patients suffering from ischemic heart disease. Additional rigorous clinical studies are needed to validate the plasma inosine/hypoxanthine concentrations, in conjunction with other current cardiac biomarkers, for a better revelation of their diagnostic potentials for early detection of acute cardiac ischemia.     

The molecular basis of erectile dysfunction: from bench to bedside

Erectile dysfunction is a common problem affecting many men across all age groups. Its etiology is multifactorial. Hormonal, vascular, neurogenic, lifestyle, and psychological entities have all been implicated as causative agents. The molecular basis underlying its etiology and progression is complex and still challenges researchers in the field. Nonetheless, newly discovered common pathways and targets of its pathogenesis have opened a new era for both prevention and active treatment of the disease. This review describes some of the known molecular mechanisms contributing to erectile dysfunction and discusses the future of gene therapy for the disease.     

Back to the future: education for systems-level biologists

We describe a graduate course in quantitative biology that is based on original path-breaking papers in diverse areas of biology; each of these papers depends on quantitative reasoning and theory as well as experiment. Close reading and discussion of these papers allows students with backgrounds in physics, computational sciences or biology to learn essential ideas and to communicate in the languages of disciplines other than their own.