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At least 487 records · Page 27Linked to original sources
PubMed2004

Untangling multi-gene families in plants by integrating proteomics into functional genomics.

The classification and study of gene families is emerging as a constructive tool for fast tracking the elucidation of gene function. A multitude of technologies can be employed to undertake this task including comparative genomics, gene expression studies, sub-cellular localisation studies and proteomic analysis. Here we focus on the growing role of proteomics in untangling gene families in model plant species. Proteomics can specifically identify the products of closely related genes, can determine their abundance, and coupled to affinity chromatography and sub-cellular fractionation studies, it can even provide location within cells and functional assessment of specific proteins. Furthermore global gene expression analysis can then be used to place a specific family member in the context of a cohort of co-expressed genes. In model plants with established reverse genetic resources, such as catalogued T-DNA insertion lines, this gene specific information can also be readily used for a wider assessment of specific protein function or its capacity for compensation through assessing whole plant phenotypes. In combination, these resources can explore partitioning of function between members and assess the level of redundancy within gene families.

Arabidopsis↗
PubMed2006

Computational prediction of genomic functional cores specific to different microbes.

Computational and experimental attempts tried to characterize a universal core of genes representing the minimal set of functional needs for an organism. Based on the increasing number of available complete genomes, comparative genomics has concluded that the universal core contains < 50 genes. In contrast, experiments suggest a much larger set of essential genes (certainly more than several hundreds, even under the most restrictive hypotheses) that is dependent on the biological complexity and environmental specificity of the organism. Highly biased genes, which are generally also the most expressed in translationally biased organisms, tend to be over represented in the class of genes deemed to be essential for any given bacterial species. This association is far from perfect; nevertheless, it allows us to propose a new computational method to detect, to a certain extent, ubiquitous genes, nonorthologous genes, environment-specific genes, genes involved in the stress response, and genes with no identified function but highly likely to be essential for the cell. Most of these groups of genes cannot be identified with previously attempted computational and experimental approaches. The large variety of life-styles and the unusually detectable functional signals characterizing translationally biased organisms suggest using them as reference organisms to infer essentiality in other microbial species. The case of small parasitic genomes is discussed. Data issued by the analysis are compared with previous computational and experimental studies. Results are discussed both on methodological and biological grounds.

Bacillus subtilis↗
PubMed2004

Genome function--a virus-world view.

By studying viruses one may begin to understand how static genomes can define dynamic processes of development. This talk will describe some of the approaches we are taking, using computer simulations and laboratory experiments, to account for the many molecular-level processes and interactions that occur when a common bacterium, E. coli, is infected by one of its viruses, phage T7. We accounted for processes of phage genome entry, transcription, translation, and DNA replication, including protein-DNA and protein-protein regulatory interactions, and we predicted the dynamics of phage progeny formation. The simulations have enabled us to identify limiting host-cell resources in phage growth, discover novel anti-viral strategies, and suggest frameworks for mining data from global mRNA and protein studies.

Bacteriophage T7↗
PubMed2000

Functional genomics with protein-protein interactions.

Knowing the sequence of a gene does not mean knowing its function. Although, information stored at the DNA level can be used to predict biological processes, proteins are the final executors of the various response programs of a cell. Transient information, like posttranslational modifications or interactions among proteins, cannot be deduced from DNA sequences. The rapid accumulation of large amounts of DNA sequence data in genomics projects has led to an increasing demand for powerful tools to analyze proteins and their behaviour at a large scale. This review aims to compare different technologies used for identification of interacting proteins and discusses recent developments in the field of high-throughput protein-protein interaction mapping.

Bacteriophages↗
PubMed2001

Functional genomics and proteomics--the role of nuclear medicine.

Now that the sequencing of the human genome has been completed, the basic challenges are finding the genes, locating their coding regions and predicting their functions. This will result in a new understanding of human biology as well as in the design of new molecular structures as potential novel diagnostic or drug discovery targets. The assessment of gene function may be performed using the tools of the genome program. These tools represent high-throughput methods used to evaluate changes in the expression of many or all genes of an organism at the same time in order to investigate genetic pathways for normal development and disease. This will lead to a shift in the scientific paradigm: In the pre-proteomics era, functional assignments were derived from hypothesis-driven experiments designed to understand specific cellular processes. The new tools describe proteins on a proteome-wide scale, thereby creating a new way of doing cell research which results in the determination of three-dimensional protein structures and the description of protein networks. These descriptions may then be used for the design of new hypotheses and experiments in the traditional physiological, biochemical and pharmacological sense. The evaluation of genetically manipulated animals or newly designed biomolecules will require a thorough understanding of physiology, biochemistry and pharmacology and the experimental approaches will involve many new technologies, including in vivo imaging with single-photon emission tomography and positron emission tomography. Nuclear medicine procedures may be applied for the determination of gene function and regulation using established and new tracers or using in vivo reporter genes such as enzymes, receptors, antigens or transporters. Pharmacogenomics will identify new surrogate markers for therapy monitoring which may represent potential new tracers for imaging. Also, drug distribution studies for new therapeutic biomolecules are needed, at least during preclinical stages of drug development. Finally, new biomolecules will be developed by bioengineering methods which may be used for isotope-based diagnosis and treatment of disease.

Animals↗
PubMed2001

Functional genomics: the worm scores a knockout.

Following the completion of the genome sequence of Caenorhabditis elegans, four independent studies have now assessed the functions of more than a third of the worm's genes by analysing the phenotypes caused when each of a large set of genes is inactivated by RNA interference.

Animals↗
PubMed2006

An integrated approach to functional genomics: construction of a novel reporter gene fusion library for Sinorhizobium meliloti.

As a means of investigating gene function, we developed a robust transcription fusion reporter vector to measure gene expression in bacteria. The vector, pTH1522, was used to construct a random insert library for the Sinorhizobium meliloti genome. pTH1522 replicates in Escherichia coli and can be transferred to, but cannot replicate in, S. meliloti. Homologous recombination of the DNA fragments cloned in pTH1522 into the S. meliloti genome generates transcriptional fusions to either the reporter genes gfp(+) and lacZ or gusA and rfp, depending on the orientation of the cloned fragment. Over 12,000 fusion junctions in 6,298 clones were identified by DNA sequence analysis, and the plasmid clones were recombined into S. meliloti. Reporter enzyme activities following growth of these recombinants in complex medium (LBmc) and in minimal medium with glucose or succinate as the sole carbon source allowed the identification of genes highly expressed under one or more growth condition and those expressed at very low to background levels. In addition to generating reporter gene fusions, the vector allows Flp recombinase-directed deletion formation and gene disruption, depending on the nature of the cloned fragment. We report the identification of genes essential for growth on complex medium as deduced from an inability to recover recombinants from pTH1522 clones that carried fragments internal to gene or operon transcripts. A database containing all the gene expression activities together with a web interface showing the precise locations of reporter fusion junctions has been constructed (www.sinorhizobium.org).

Bacterial Proteins↗
PubMed2003

Genetic Models in Applied Physiology. Functional genomics in the mouse: powerful techniques for unraveling the basis of human development and disease.

Now that near-complete DNA sequences of both the mouse and human genomes are available, the next major challenge will be to determine how each of these genes functions, both alone and in combination with other genes in the genome. The mouse has a long and rich history in biological research, and many consider it a model organism for the study of human development and disease. Over the past few years, exciting progress has been made in developing techniques for chromosome engineering, mutagenesis, mapping and maintenance of mutations, and identification of mutant genes in the mouse. In this mini-review, many of these powerful techniques will be presented along with their application to the study of development, physiology, and disease.

Animals↗
PubMed1997

Functional genomics in mice by tagged sequence mutagenesis.

Most mammalian genes will soon be characterized as cDNA sequences with little information about their function. To utilize this sequence information for large-scale functional studies, a gene trap retrovirus shuttle vector has been developed to disrupt genes expressed in murine embryonic stem (ES) cells. A library of mutant clones was isolated, and regions of genomic DNA adjacent to 400 independent provirus inserts were cloned and sequenced. The flanking sequences, designated 'promoter-proximal sequence tags', or PSTs, identified 63 specific genes and anonymous cDNAs disrupted as a result of virus integration. The efficiency of tagged sequence mutagenesis suggests that many of the 10,000-20,000 genes expressed in ES cells can be targeted, providing defined mutations for the analysis of gene functions in vivo. In addition, PSTs provide the first expressed sequence tags derived from genomic DNA, and define gene features such as exon boundaries and promoters that are missing from cDNA sequences.

Animals↗
PubMed2004

Comparative map and trait viewer (CMTV): an integrated bioinformatic tool to construct consensus maps and compare QTL and functional genomics data across genomes and experiments.

In the past few decades, a wealth of genomic data has been produced in a wide variety of species using a diverse array of functional and molecular marker approaches. In order to unlock the full potential of the information contained in these independent experiments, researchers need efficient and intuitive means to identify common genomic regions and genes involved in the expression of target phenotypic traits across diverse conditions. To address this need, we have developed a Comparative Map and Trait Viewer (CMTV) tool that can be used to construct dynamic aggregations of a variety of types of genomic datasets. By algorithmically determining correspondences between sets of objects on multiple genomic maps, the CMTV can display syntenic regions across taxa, combine maps from separate experiments into a consensus map, or project data from different maps into a common coordinate framework using dynamic coordinate translations between source and target maps. We present a case study that illustrates the utility of the tool for managing large and varied datasets by integrating data collected by CIMMYT in maize drought tolerance research with data from public sources. This example will focus on one of the visualization features for Quantitative Trait Locus (QTL) data, using likelihood ratio (LR) files produced by generic QTL analysis software and displaying the data in a unique visual manner across different combinations of traits, environments and crosses. Once a genomic region of interest has been identified, the CMTV can search and display additional QTLs meeting a particular threshold for that region, or other functional data such as sets of differentially expressed genes located in the region; it thus provides an easily used means for organizing and manipulating data sets that have been dynamically integrated under the focus of the researcher's specific hypothesis.

Adaptation, Physiological↗
PubMed2003

Membrane restraint of estrogen receptor alpha enhances estrogen-dependent nuclear localization and genomic function.

Estrogen receptor (ER) alpha localizes to both the nucleus and the plasma membrane, mediating estrogen-dependent genomic and nongenomic signaling, respectively. In some cells, ERalpha appears to be excluded from the nucleus, and it is unclear whether genomic signaling takes place. The purpose of this study was to determine whether membrane-associated ERalpha is capable of genomic signaling, or whether this pool of receptors strictly serves membrane-mediated signaling. ERalpha fused to the C-terminal cytoplasmic tail of bovine rhodopsin (Rh-ERalpha) activates ER response element-dependent transcription only in the presence of estrogen; the activity is antagonized by the estrogen antagonist ICI 182,780 and by the dominant-negative mutant of ERalpha and is unaffected by inhibitors of MAPKs and Akt signaling, indicating that this was due to direct genomic action. The activity of Rh-ERalpha containing the activating Y537S mutation was also estrogen dependent, suggesting that estrogen gated the entry of Rh-ERalpha into the nucleus. Indeed, cell fractionation studies demonstrated that Rh-ERalpha protein, in contrast to ERalpha that was nuclear at baseline, was excluded from the nucleus in the absence of hormone, and localized to the inner nuclear membrane on incubation with estrogen. These data demonstrate that membrane tethered ERalpha is capable of nuclear function and that its transcriptional activity is regulated by hormone-dependent entry into the inner nuclear membrane. Furthermore, these experiments provide evidence that under certain circumstances, membrane proteins are capable of nuclear function without detectable nucleoplasmic localization.

5' Untranslated Regions↗
PubMed2004

Innate immunity in the malaria vector Anopheles gambiae: comparative and functional genomics.

The resurgence of malaria is at least partly attributed to the absence of an effective vaccine, parasite resistance to antimalarial drugs and resistance to insecticides of the anopheline mosquito vectors. Novel strategies are needed to combat the disease on three fronts: protection (vaccines), prophylaxis/treatment (antimalarial drugs) and transmission blocking. The latter entails either killing the mosquitoes (insecticides), preventing mosquito biting (bednets and repellents), blocking parasite development in the vector (transmission blocking vaccines), genetic manipulation or chemical incapacitation of the vector. During the past decade, mosquito research has been energized by several breakthroughs, including the successful transformation of anopheline vectors, analysis of gene function by RNAi, genome-wide expression profiling using DNA microarrays and, most importantly, sequencing of the Anopheles gambiae genome. These breakthroughs helped unravel some of the mechanisms underlying the dynamic interactions between the parasite and the vector and shed light on the mosquito innate immune system as a set of potential targets to block parasite development. In this context, putative pattern recognition receptors of the mosquito that act as positive and negative regulators of parasite development have been identified recently. Characterizing these molecules and others of similar function, and identifying their ligands on the parasite surface, will provide clues on the nature of the interactions that define an efficient parasite-vector system and open up unprecedented opportunities to control the vectorial capacity of anopheline mosquitoes.

Animals↗
PubMed2001

A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations.

A large proportion of the 6,000 genes present in the genome of Saccharomyces cerevisiae, and of those sequenced in other organisms, encode proteins of unknown function. Many of these genes are "silent, " that is, they show no overt phenotype, in terms of growth rate or other fluxes, when they are deleted from the genome. We demonstrate how the intracellular concentrations of metabolites can reveal phenotypes for proteins active in metabolic regulation. Quantification of the change of several metabolite concentrations relative to the concentration change of one selected metabolite can reveal the site of action, in the metabolic network, of a silent gene. In the same way, comprehensive analyses of metabolite concentrations in mutants, providing "metabolic snapshots," can reveal functions when snapshots from strains deleted for unstudied genes are compared to those deleted for known genes. This approach to functional analysis, using comparative metabolomics, we call FANCY-an abbreviation for functional analysis by co-responses in yeast.

Adenine Nucleotides↗
PubMed2006

Functional genomics approaches for the study of sporadic adrenal tumor pathogenesis: clinical implications.

Although sporadic adrenal tumors are frequently encountered in the general population their pathogenesis is not well elucidated. The advent of functional genomics/bioinformatics tools enabling large scale comprehensive genome expression profiling should contribute to significant progress in this field. Some studies have already been published describing gene expression profiles of benign and malignant adrenocortical tumors and phaeochromocytomas. Several genes coding for growth factors and their receptors, enzymes involved in steroid hormone biosynthesis, genes related to the regulation of cell cycle, cell proliferation, adhesion and intracellular metabolism have been found to be up- or downregulated in various tumors. Some alterations in gene expression appear so specific for certain tumor types that their application in diagnosis, determination of prognosis and the choice of therapy can be envisaged. In this short review, the authors will present a synopsis of these recent findings that seem to open new perspectives in adrenal tumor pathogenesis, with emphasis on changes in steroidogenic enzyme expression profiles and highlighting possible clinical implications.

Adrenal Gland Neoplasms↗
PubMed2002

Bioinformatics, functional genomics, and proteomics study of Bacillus sp.

The ability of bioinformatics to characterize genomic and proteomic sequences from bacteria Bacillus sp. for prediction of genes and proteins has been evaluated. Genomics coupling with proteomics, which is relied on integration of the significant advances recently achieved in two-dimensional (2-D) electrophoretic separation of proteins and mass spectrometry (MS), are now important and high throughput techniques for qualifying and analyzing gene and protein expression, discovering new gene or protein products, and understanding of gene and protein functions including post-genomic study. In addition, the bioinformatics of Bacillus sp. is embraced into many databases that will facilitate to rapidly search the information of Bacillus sp. in both genomics and proteomics. It is also possible to highlight sites for post-translational modifications based on the specific protein sequence motifs that play important roles in the structure, activity and compartmentalization of proteins. Moreover, the secreted proteins from Bacillus sp. are interesting and widely used in many applications especially biomedical applications that are the highly advantages for their potential therapeutic values.

Bacillus↗
PubMed2003

Inducible expression system and marker-linked mutagenesis approach for functional genomics of Haemophilus influenzae.

Complete bacterial genomic DNA sequences have allowed application of genome-scale strategies to identify essential genes. Efficient generation of conditional loss of function mutations provides a means of characterization of this class of genes. Promoter systems conferring tight regulation are particularly applicable to generating such mutations and we sought to apply this approach for the analysis of an essential gene of Haemophilus influenzae. Therefore, we developed the use of a D-xylose-inducible promoter for verification of an essential role in growth for yraM, which encodes a putative periplasmic lipoprotein, in both H. influenzae Rd and virulent type b strains. This promoter was sufficiently tightly regulated to generate conditionally viable strains by inducible expression of YraM. A second approach was used to further characterize YraM. Natural transformation and an ordered mutant collection spanning the H. influenzae genome provide the means to target any gene of interest for mutagenesis and temperature-sensitive (TS) mutant isolation. This strategy was applied to generate a conditionally lethal allele of yraM. The resulting TS mutation was directly mapped to a single amino acid substitution within a motif conserved in all putative YraM orthologs and this mutation was shown to be sufficient to confer the TS phenotype.

Bacterial Proteins↗
PubMed2002

Functional genomics of ionotropic acetylcholine receptors in Caenorhabditis elegans and Drosophila melanogaster.

Genetics, genomics and electrophysiology are transforming our understanding of the nicotinic acetylcholine receptors (nAChRs). Caenorhabditis elegans contains the largest known family of nAChR subunit genes (27 members), while Drosophila melanogaster contains an exclusively neuronal nAChR gene family (10 members). In C. elegans, several genetic screens have enabled the identification of nAChR subunits, along with novel proteins that act upstream and downstream of functional nAChRs. The C. elegans genome project has identified many new candidate nAChR subunits and the calculated electrostatic potential energy profiles for the M2 channel-lining regions predict considerable functional diversity. The respective roles of subunits are under investigation using forward and reverse genetics. Electrophysiological and reporter gene studies have demonstrated roles for particular subunits in levamisole-sensitive muscle nAChRs and a role for nAChRs in pharyngeal pumping. Recombinant homomeric and heteromeric C. elegans nAChRs have been expressed in Xenopus laevis oocytes. In D. melanogaster, three new nAChR a subunits have been cloned, one of which shows multiple variant transcripts arising from alternative splicing and A-to-I pre-mRNA editing. Thus, studies on the genetic model organisms C. elegans and D. melanogaster have revealed different routes to generating molecular and functional diversity in the nAChR gene family and are providing new insights into the in vivo functions of individual family members.

Animals↗
PubMed2003

Structural and functional genomics and evolutionary relationships in the cluster of genes encoding murine 2',5'-oligoadenylate synthetases.

2',5'-Oligoadenylate synthetases (2',5'-OASs) are interferon-inducible enzymes. Some of these proteins play an important role in cellular physiology, in particular, in the innate defense mechanisms against RNA virus infections. In the present publication we report the complete genomic structure of the cluster of genes encoding mouse 2',5'-OAS, with all its transcription units, their predicted functions, and their evolutionary relationships. We found that mouse Oas2/Oas3 genes have a genomic structure similar to that of human OAS2/OAS3, while the mouse equivalent of human OAS1 is composed of eight (Oas1a to Oas1h) tandemly arranged transcription units. For all these eight genes a specific inducible promoter controls transcription. The possible functions of this family of proteins are discussed.

2',5'-Oligoadenylate Synthetase↗