Transfected cell microarrays: an efficient tool for high-throughput functional analysis

Transfected cell microarrays are considered to be a breakthrough methodology for high-throughput and high-content functional genomics. Here, recent advances in the cell microarray field are reviewed, along with its potential to increase the speed of determining gene function. These advances, combined with an increasing number and diversity of gene perturbing systems, such as RNAi and ectopic gene expression, provide tools for expanding our understanding of biology at the systems level.     

Gene expression systems for lactic acid bacteria.

Considerable advances have been made in the genetics and molecular biology of lactic acid bacteria, including Lactococcus, Lactobacillus, Leuconostoc, Pediococcus and Streptococcus spp. These have resulted in the construction of constitutive gene expression cassettes, inducible gene expression systems, and specific protein targeting systems for these bacteria. These developments are important in the food industry where lactic acid bacteria can be exploited as food-grade cell factories.     

Application of a systems approach to study developmental gene regulation

All cells in a multicellular organism contain the same genome, yet different cell types express different sets of genes. Recent advances in high throughput genomic technologies have opened up new opportunities to understand the gene regulatory network in diverse cell types in a genome-wide manner. Here, I discuss recent advances in experimental and computational approaches for the study of gene regulation in embryonic development from a systems perspective. This review is written for computational biologists who have an interest in studying developmental gene regulation through integrative analysis of gene expression, chromatin landscape, and signaling pathways. I highlight the utility of publicly available data and tools, as well as some common analysis approaches.     

新的药物传递系统:外泌体作为药物载体递送*

外泌体(exosomes)是细胞分泌的囊泡,在细胞与细胞之间通信中发挥重要作用。由于其固有的长距离通信能力和出色的生物相容性而具有很大的潜力作为药物递送载体,尤其适合递送蛋白质、核酸、基因治疗剂等治疗药物。许多研究表明外泌体可以有效地将许多不同种类的货物递送至靶细胞,因此,它们常被作为药物载体用于治疗。对外泌体作为药物递送系统中面临的外泌体分离,药物装载和靶向治疗应用的进展与挑战作一介绍,以期更好为外泌体药物递送系统开发提供新思路。     

基因治疗的发展现状、问题和展望

基因治疗是一种新的治疗手段,可以治疗多种疾病,包括癌症、遗传性疾病、感染性疾病、心血管疾病和自身免疫性疾病。癌症基因治疗是基因治疗的主要应用领域。过去几年里,全球基因治疗临床试验取得了很大的进步。实际上,基因治疗也遇到了很多困难。未来,基因治疗的主要目标是发展安全和高效的基因导入系统,它们能将外源遗传物质靶向性地导入到特异的细胞。本文主要综述基因治疗所取得的突出进展、所遇到的困难和发展前景。     

基因治疗的应用及研究进展

基因治疗是一种新的治疗手段,可用于癌症、遗传性疾病、感染性疾病、心血管疾病和自身免疫性疾病等的治疗。癌症基因治疗是基因治疗的主要应用领域。过去几年里,全球基因治疗临床试验取得了很大的进步,也遇到了很多困难。未来基因治疗的主要目标是发展安全和高效的基因导入系统,它们能将外源遗传物质靶向性地导入特异的细胞。简要综述了基因治疗研究和应用的进展、困难及其发展前景。     

Gene correction in patient-specific iPSCs for therapy development and disease modeling

The discovery that mature cells can be reprogrammed to become pluripotent and the development of engineered endonucleases for enhancing genome editing are two of the most exciting and impactful technology advances in modern medicine and science. Human pluripotent stem cells have the potential to establish new model systems for studying human developmental biology and disease mechanisms. Gene correction in patient-specific iPSCs can also provide a novel source for autologous cell therapy. Although historically challenging, precise genome editing in human iPSCs is becoming more feasible with the development of new genome-editing tools, including ZFNs, TALENs, and CRISPR. iPSCs derived from patients of a variety of diseases have been edited to correct disease-associated mutations and to generate isogenic cell lines. After directed differentiation, many of the corrected iPSCs showed restored functionality and demonstrated their potential in cell replacement therapy. Genome-wide analyses of gene-corrected iPSCs have collectively demonstrated a high fidelity of the engineered endonucleases. Remaining challenges in clinical translation of these technologies include maintaining genome integrity of the iPSC clones and the differentiated cells. Given the rapid advances in genome-editing technologies, gene correction is no longer the bottleneck in developing iPSC-based gene and cell therapies; generating functional and transplantable cell types from iPSCs remains the biggest challenge needing to be addressed by the research field.     

"Quorum sensing", or how bacteria "talk" to each other

Recent advances in studying the quorum-sensing systems, which regulate gene expression depending on population density, are reviewed. Low-molecular-weight acyl derivatives of L-homoserine lactone (N-AHL) freely diffuse through cell membranes and determine cell-to-cell communications in bacteria. The quorum-sensing systems have first been found to regulate bioluminescence in marine bacteria Photobacterium (Vibrio) fischeri and Vibrio harveyi. Such systems are widespread and control expression of genes for virulence factors, proteases, antibiotics, etc., in various Gram-negative bacteria, including plant, animal, and human pathogens. Quorum sensing is a prominent example of social behavior in bacteria, as signal exchange among individual cells allows the entire population to choose an optimal way of interaction with the environment and with higher organisms.     

Artificial mammalian gene regulation networks-novel approaches for gene therapy and bioengineering

Recently developed strategies for targeted molecular interventions in mammalian cells have created novel opportunities in biotechnological and biomedical research with huge economic and therapeutic impact: the design of mammalian cells with desired phenotypes for biopharmaceutical manufacturing, tissue engineering and gene therapy. These advances have been enabled by constructing artificial gene regulation systems with control modalities similar to those evolved in key regulatory networks of mammalian cells. This review highlights recurring cellular regulation strategies and artificial gene regulation technology currently in use for rational reprogramming of cellular key events including metabolism, growth, differentiation and cell death to achieve sophisticated bioprocess and therapeutic goals.     

Gene targeting and somatic cell genetics--a rebirth or a coming of age?

A number of recent advances have significantly facilitated gene targeting in somatic cells. Gene targeting can now be performed with the same ease and efficiency in somatic cells as in murine embryonic stem cells. Rigorous genetic analyses can therefore be applied for the first time to the large number of excellent human cell culture systems. These tools will be important in areas where rodent models do not adequately represent human biology.     

Inroads into the structure and function of intermediate filament networks

Although intermediate filaments are one of three major cytoskeletal systems of vertebrate cells, they remain the least understood with respect to their structure and function. This is due in part to the fact that they are encoded by a large gene family which is developmentally regulated in a cell and tissue type specific fashion. This article is in honor of Ueli Aebi. It highlights the studies on IF that have been carried out by our laboratory for more than 40 years. Many of our advances in understanding IF are based on conversations with Ueli which have taken place during adventurous and sometimes dangerous hiking and biking trips throughout the world.     

The epigenomics of cancer

Aberrant gene function and altered patterns of gene expression are key features of cancer. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause this dysregulation. Here, we review recent advances in understanding how epigenetic alterations participate in the earliest stages of neoplasia, including stem/precursor cell contributions, and discuss the growing implications of these advances for strategies to control cancer.     

Quorum Sensing,or How Bacteria “Talk” to Each Other

Reviewed are recent advances in studying the quorum-sensing systems, which regulate gene expression depending on population density. Low-molecular-weight acyl derivatives of L-homoserine lactone (N-AHL) freely diffuse through cell membranes and determine cell-to-cell communication in bacteria. The quorum-sensing systems have first been found to regulate bioluminescence in marine bacteria Photobacterium(Vibrio) fischeriand Vibrio harveyi. Such systems are widespread and control expression of genes for virulence factors, proteases, antibiotics, etc., in various Gram-negative bacteria, including plant, animal, and human pathogens. Quorum sensing is a prominent example of social behavior in bacteria, as signal exchange among individual cells allows the entire population to choose an optimal way of interaction with the environment and with higher organisms.     

乳酸菌食品级基因表达系统

酸菌是一类重要工业菌株。最近,乳酸菌遗传学和分子生物学的研究取得长足进步,导致发展了乳酸菌食品级基因表达系统。通过介绍乳酸菌食品级基因表达系统的基本要求、食品级选择性标记、食品级诱导物及该系统的研究进展,展示了乳酸菌食品级基因表达系统的建立对研究乳酸菌的基因表达调控和它的深层次的开发利用所具有的重要意义。     

Protein and Genome Evolution in Mammalian Cells for Biotechnology Applications

Mutation and selection are the essential steps of evolution. Researchers have long used in vitro mutagenesis, expression, and selection techniques in laboratory bacteria and yeast cultures to evolve proteins with new properties, termed directed evolution. Unfortunately, the nature of mammalian cells makes applying these mutagenesis and whole-organism evolution techniques to mammalian protein expression systems laborious and time consuming. Mammalian evolution systems would be useful to test unique mammalian cell proteins and protein characteristics, such as complex glycosylation. Protein evolution in mammalian cells would allow for generation of novel diagnostic tools and designer polypeptides that can only be tested in a mammalian expression system. Recent advances have shown that mammalian cells of the immune system can be utilized to evolve transgenes during their natural mutagenesis processes, thus creating proteins with unique properties, such as fluorescence. On a more global level, researchers have shown that mutation systems that affect the entire genome of a mammalian cell can give rise to cells with unique phenotypes suitable for commercial processes. This review examines the advances in mammalian cell and protein evolution and the application of this work toward advances in commercial mammalian cell biotechnology.