Technologies map: Guide to terms in these glossaries    Site Map
Related glossaries include Applications: Drug discovery & development Functional genomics, Genomics, Metabolic engineering, Phylogenomics Proteomics
Informatics: Bioinformatics, Cheminformatics
Technologies:  Bioprocessing   Gene amplification & PCR   Microarrays
Biology: Cell biology, Gene definitions, Pharmaceutical biology, Proteins,  RNA SNPs & other genetic variations

animal models: Functional genomics

antibody display:  de Kruif J,, Boel E, Logtenberg T. Selection and application of human single chain Fv antibody fragments from a semi-synthetic phage antibody display library with designed CDR3 regions. J Mol Biol. 1995 Apr 21;248 (1): 97-105, April 1995 .

Google = about 17,200 Nov 13, 2006

antisense: Pharmaceutical biology

aptamer: Oligonucleotide which displays specific binding to a protein or other target, often selected by an iterative cycle of affinity- based enrichment.

Narrower term: Functional genomics peptide aptamer Related term: SELEX. [IUPAC Combinatorial Chemistry]

BAC: See Bacterial Artificial Chromosome.

Bacterial artificial chromosome (BAC): A vector used to clone DNA fragments (100- to 300-kb insert size; average, 150 kb) in Escherichia coli cells. Based on naturally occurring F-factor plasmid found in the bacterium E. coli. Compare cloning vector.  [DOE] 

DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes. MeSH, 2002

Related term: BAC maps. Maps, genetic & genomic

bacteriophage: Many phage have proved useful in the study of molecular biology and as vectors for the transfer of genetic information between cells … lambda bacteriophage can also undergo a lytic cycle or can enter a lysogenic cycle, in which the page DNA is incorporated into that of the host, awaiting a signal that initiates events leading to replication of the virus and lysis of the host cell. [Glick]  

The workhorse of phage display is the M13 bacteriophage virus. 

Related terms: phage, phage display bacteriophage, biopanning, phage;  Labels, signaling & detection     Proteomics directed protein evolution

biochemical genomics: Chemistry & biology

biotechnology: The integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof  and molecular analogues for products and services. [IUPAC Compendium] 

It is important to understand the distinction between biotechnology as a new process technology and as a drug discovery research tool. The first uses genetic engineering to manufacture large molecular weight drugs that cannot be directly synthesized or extracted. The second involves understanding the molecular basis of disease and the search for new therapeutic targets  using techniques such as cloned receptors as screens or transgenic organisms created through gene knock-out technologies to determine protein function; most of the focus is on small molecule drugs that interact against those targets. As the pharmaceutical industry is using biotechnology in drug discovery, it will likely maintain its dominant position in small molecules, but the development and manufacture of protein based therapeutics requires a completely different set of core competencies. Product Definition, The Biopharmaceutical Sector, Industry Canada, 2003 http://strategis.ic.gc.ca/epic/internet/inbio-pha.nsf/en/df00020e.html#2.1

Related terms: Business of biotechnology biotechnology firms, biotechnology industry 
biopharmaceuticals: Drug approvals   biotechnology drugs: Drug approvals

BioTech blog http://biotechblog.com/ Articles from Signals (Recombinant Capital), Mass High Tech, Wired medtech, New Scientist, Boston Globe and others. 
Corante: Biotechnology http://www.corante.com/biotech/
Corante: In the Pipeline http://www.corante.com/pipeline/
SimpleTrend: BioTech http://startsimple.com/trend/biotech/index.html

Related term: Business of biopharmaceuticals biotechnology industry 

cDNA phage display:  Display cloning: functional identification of natural product receptors using cDNA-phage display.  Sche PP, McKenzie KM, White JD, Austin DJ. Chem Biol. 1999 Oct;6(10):707- 716

Google = about 537 Nov 13, 2006

chemical genetics, chemical genomics, chemogenomics: Dr Chemistry & biology

chemical mutagenesis:  Systematic mutagenesis using chemical with mutagenic properties.

chemical proteomics: Chemistry & biology

clone: A population of genetically identical cells produced from a common ancestor. Sometimes also used to refer to a number of recombinant DNA molecules all carrying the same inserted sequence. [IUPAC Medicinal Chemistry, IUPAC Compendium] 

Clone was coined by Herbert J. Webber in 1903 for "a colony of organisms derived asexually from a single progenitor" and was quickly adopted by botanists and cell biologists. But the popular perception of cloning can be traced to Alvin Toffler's Future Shock (1970) and was quickly popularized (and extended to items such as computers). But Lee Silver, Professor of Molecular Biology and Public Affairs, Princeton Univ. concludes that "the scientific community has lost control over Webber's pleasant sounding little word. Cloning has a popular connotation that is impossible to dislodge. We must accept that democratic debate on cloning is bereft of any meaning. Science and Scientists would be better served by choosing other words to explain advances in developmental biotechnology to the public". [L. Silver "What are clones? They're not what you think they are" Nature 412 (6842): 21, 5 July 2001]

Narrower term: clone bank

clone bank: Genomic library, a collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. [Schlindwein] 

Related term: genomic library

cloning: Using specialized DNA technology (see cloning vector) to produce multiple, exact copies of a single gene or other segment of DNA to obtain enough material for further study. This process is used by researchers in the Human Genome Project, and is referred to as cloning DNA. The resulting cloned (copied) collections of  DNA molecules are called clone libraries. A second type of cloning exploits the natural process of cell division to make many copies of an entire cell. The genetic makeup of these cloned cells, called a cell line, is identical to the original cell. A third type of cloning produces complete, genetically identical animals such as the famous  Scottish sheep, Dolly.  [DOE] 

The process of making copies of a specific piece of DNA, usually a gene. When geneticists speak of cloning, they do not mean the process of making genetically identical copies of an entire organism. [NHGRI]

Cloning, US President's Council on Bioethics http://www.bioethics.gov/topics/cloning_index.html

Cloning & nuclear transfer: A short glossary, Mike McKeen,  Roslin Institute Online, Scotland, 1999  http://www.ri.bbsrc.ac.uk/library/research/cloning/glossary.html#clon

Cloning and nuclear transfer: moral and ethical concerns, Harry Griffin, Ian Wilmut, Grahame Bulfield, Roslin Institute, Scotland, 1998  http://www.ri.bbsrc.ac.uk/library/research/cloning/nt-ethics.html

Dolly the sheep, Nature http://www.nature.com/nature/dolly/

Of course many plants can be cloned (cuttings). And identical twins are (in a technical sense) clones, who can be organ donors for each other without immunosuppressants

Related terms: enucleated, directed evolution, molecular evolution, nuclear transfer, quiescence;  Narrower terms:

cloning vector: DNA molecule originating from a virus, a plasmid, or the cell of a higher organism into which another DNA fragment of appropriate size can be integrated without loss of the vectors capacity for self replication; vectors introduce foreign DNA into host cells, where it can be reproduced in large quantities. Examples are plasmids, cosmids, and yeast artificial chromosomes [YACs]; vectors are often recombinant molecules containing DNA sequences from several sources. [DOE]

comparative genomics: Functional genomics

comparative systems biology: My research projects in comparative systems biology have four main thrusts: whole-genome functional annotation, multi-clustering of molecular profiles, cross-condition analysis of functional genomics data, and computationally-driven design of biological experiments. The research I am conducting with my life science colleagues in comparative systems biology has the goal of providing precise functional annotations to hypothetical genes in model organisms and in newly-sequenced genomes; delineating similarities and differences in cellular networks activated in different diseases; identifying core cellular pathways common to response networks for multiple stresses in various model organisms; and refining our understanding of the molecular basis of disease resistance in plant-pathogen interactions. Research interests, TM Murali, Computer Sciences, Virginia Tech, http://people.cs.vt.edu/~murali/research.html

Google = about 126 May 7, 2007, about 203 Oct. 15, 2007

Broader term: systems biology

conditional knockout: A method by which a gene can be switched off and on. 

Connectivity Map, cMap: A collection of genome-wide transcriptional expression data from cultured human cells treated with bioactive small molecules and simple pattern-matching algorithms that together enable the discovery of decisive functional connections between drugs, genes and diseases through the transitory feature of common gene expression changes. Broad Institute, MIT, Connectivity Map   http://www.broad.mit.edu/cmap/ 

Cre-lox: Tissue- specific gene deletion. 

A bacteriophage- derived, site- specific recombinase called Cre is used to selectively introduce a deletion into a particular cellular compartment. The method basically involves introducing loxP target sequences into the gene to be deleted, and engineering expression of the Cre recombinase enzyme under the control of a tissue- specific promoter. Thus, the enzyme is expressed only in the desired tissue, and it deletes the gene of interest via the loxP target sites.) 

display technologies: We will be covering a range of display methods that are being used to create diverse repertoires of functionally diverse biopharmaceuticals. New classes of compounds and synthetic biologics are being translated by display to a biologically active drug. There are a number of success stories where display methodologies have been used to generate drug candidates that are currently in the clinic.  

See also antibody display, cDNA display, phage display, peptide display, ribosome display  

DNA shuffling: The use of DNA recombination ( RECOMBINATION, GENETIC) to prepare a large gene library of novel, chimeric genes from a population of randomly fragmented DNA from related gene sequences. [MeSH 2003]

A method for in vitro homologous recombination of pools of selected mutant genes by random fragmentation and polymerase chain reaction (PCR) reassembly. Computer simulations called genetic algorithms have demonstrated the importance of iterative homologous recombination for sequence evolution. WP Stemmer, Rapid evolution of a protein in vitro by DNA shuffling, Nature. 1994 Aug 4;370 (6488): 389- 391.

Google = about 4,050 Aug. 20, 2003; about 10,100 Nov. 29, 2004; about 91,800 Nov 13, 2007

Related/equivalent? term: gene shuffling. Related terms: domain shuffling, exon shuffling, protein shuffling

domain shuffling: Protein structure

Google = about 862 Aug. 20, 2003; about 2,030 Nov. 29, 2004; about 25,400 Nov 13, 2006

embryonic lethal trait: In some cases, knockout of a gene believed to be important in a disease occurring in adult life (such as a cancer) will be lethal to the embryo, resulting in little or no information about the function of the gene in adult cells of interest.

Related terms knockdown, synthetic lethal screening

enucleated: Cell from which the nucleus has been removed, used for nuclear transfer to produce a cloned animal from differentiated cells. 

Related terms: cloning, nuclear transfer, quiescence

epigenetic, epigenetics:  Genetic variations & SNPs

epigenome, epigenomics: -Omes & -omics

evolutionary genomics, evolutionary homology: Phylogenomics

exon shuffling theory: Contends that introns act as spacers where breaks for genetic recombination occur. Under this scenario, exons - which usually contain instructions for building a protein subunit - remain intact when shuffled during recombination. In this way, proteins with new functional repertoires can evolve.  [Peter Schmidt, "Shuffling, Recombination, and the Importance of ...Nonsense"  Swarthmore College]  www.swarthmore.edu/Humanities/pschmid1/array/Gnarl3/exon.html

Related terms: DNA shuffling, domain shuffling, gene shuffling, protein shuffling

Google "exon shuffling" = about 2,300 Aug. 20, 2003; about 9, 150 Nov. 29, 2004

exon trapping (exon amplification): A rapid and efficient means of finding expressed DNA sequences in a genome sequence and is based on selection for functional splice sites in genomic DNA. The advantages of exon trapping are that it does not require any prior knowledge about tissue- specific gene expression and can easily be performed on complex genomes. It can identify constitutive exons as well as alternative exons but cannot be used to identify intronless genes. [Clinical Molecular Genetics Society UK "Exon trapping" 2000] http://www.ich.ucl.ac.uk/cmgs/exontrap.htm

forward genetics: The traditional approach to genetics, which starts with a phenotype and then identifies genetic mutations or variations that control or cause that trait. CHA, Cambridge Healthtech Advisors Model Animal Systems: Emerging Applications and Commercial Opportunities in Drug Discovery and Development, report, 2004

Related term: positional cloning. Compare reverse genetics

forward genomics: Large- scale insertional mutagenesis offers several significant features as a genomics platform. DNA insertions allow rapid functional analysis of phenotypes and the associated genes in a forward genomics research program. In addition, the indexed collection of insertion mutants creates basis for a robust program in reverse genomics by which one may analyze phenotypes associated with any given gene identified only by sequence. HELENA MATHEWS "Gene Discovery in Plants by Activation Tagging" In Vitro Cell. Dev. Biol - Animal 37:3 Part II, March 2001] 

functional genomics technologies: Functional genomics

Include gene disruption, gene manipulation, gene shuffling, gene targeting, gene trapping, knockdowns, knockins, knockouts, mutagenesis, phage display, positional cloning, Post Translational Gene Silencing PTGS, RNA interference RNAi.  Related terms chemical genetics, chemical genomics

gene disruption: A key methodology in high- throughput gene functional analysis. Involves developing various methods for randomly disrupting genes throughout the genome of a model organism (resulting in knockouts, or null mutations of these genes) and then determining (1) which genes have been disrupted and (2) the phenotype (if any) of the mutant organism. 

Broader term: gene manipulation Narrower terms: knockdown, knockin, knockout, PTSG, 

gene interference: An effect similar to loss- of function mutations in organisms, as if the gene being studied were inactivated. Both sense and antisense RNA are already known to produce interference with the expression of the genes they correspond to by blocking protein synthesis. Antisense RNA is single- stranded RNA that is complementary to a particular mRNA sequence. Sense RNA, also single- stranded, is a shorter version of a particular mRNA strand. Another mechanism for gene interference using RNA has been developed in the past few years. This process, called RNA interference (RNAi) involves double- stranded RNA (dsRNA), and was first developed for use in invertebrates, later vertebrates, and now after much doubt, has been proved to work for mammals, specifically mice. [Dr. Bert Ely, Univ. of South Carolina, US]  http://www.biol.sc.edu/~elygen/caflisch.html  

Related terms gene disruption, knockout; Broader term: gene manipulation Narrower terms: PTSG, RNAi 

gene knockout: Use of particular techniques to "knock out" the function of a gene in a model organism. Studying the effects of the gene knockout can help researchers understand the function of the gene that has been inhibited. 

Related terms: gene manipulation, knockdown, knockin, knockout

gene library: A collection of cloned DNA fragments from a variety of species. [IUPAC Biotech]

gene manipulation: The use of in vitro techniques to produce DNA molecules containing novel combinations of genes or altered sequences, and the insertion of these into vectors that can be used for their incorporation into host organisms or cells in which they are capable of continued propagation of the modified genes. [IUPAC Biotech] 

Narrower terms: knockdowns, knockins, knockouts, mutagenesis, biochemical genomics, exon trapping, gene disruption, gene targeting, gene trapping;  Proteomics  protein knockouts

gene shuffling: DNA shuffling is the most powerful molecular evolution technique known to date, and it can be used to evolve proteins, plasmids and viruses in vitro. We are applying this method to improve efficacy or pharmacological properties of cytokines with therapeutic potential.... part of the project is done in collaboration with Maxygen (Santa Clara, CA), a biotechnology institute where the gene shuffling technology was developed by Dr. Willem Stemmer (Stemmer, Nature 370: 389- 391, 1994; Crameri et al. Nature 391: 288, 1998). Juha Punnonen, Role of Cytokines in Regulation of Synovial Inflammation and Evolution of Cytokines In Vitro, Dept. of Medical Microbiology, Univ. of Turku, Finland, 2000 http://www.utu.fi/research/tic/projects/punnonen.html

Encompasses techniques to speed up genetic evolution to screen for  high value proteins. Novel recombinant gene products are screened to identify candidate proteins with desired activities. 

Google = about 1,860 Aug. 20, 2003; about 5, 250 Nov. 29, 2004

Related terms: DNA shuffling, domain shuffling, exon shuffling, molecular evolution, protein shuffling, directed protein evolution gene manipulation, knockdown, knockin, knockout

gene silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. MeSH, 2000 

Refers to complex interactions between DNA (transcriptional gene silencing) and RNA (post- transcriptional gene silencing) based on the homology between these sequences, their place into the genome, the possible modifications of their chemical structure, etc. These interactions may stop the expression of a gene or lead to the degradation of its transcription products (RNA), thus "silencing" the gene as no proteins are produced anymore. Barbara Bordogna, Sustainability and Public or Private Management Glossary, Univ. Geneva, 2003  http://supprem.unige.ch/glossary/

Narrower terms: Post-Transcriptional Gene Silencing PTGS, RNA silencing; Related term: epigenetics

gene suppression: shRNA is useful where long-term gene suppression is required, or where the cells are resistant to other delivery methods. Its use, however, has been limited by lack of design and processing methods that provide reliable and reproducible gene silencing. BioIT World Weekly Update Sept 5, 2006 

Broader term: gene disruption. Related term: Cancer genomics tumor suppressor gene

gene targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [MeSH, 1995]

gene titration: Dr. [Oliver] Smithies has skillfully wielded a genetic knife - either removing or adding multiple copies of genes to mouse DNA-- to learn more about the roles these proteins play in controlling how much and how fast blood traverses vessels throughout the body. Such "gene titration" experiments, as he calls them, have helped Dr. Smithies evolve a model to describe essential hypertension, a complex disease with multiple genetic and environmental causes. These prior studies have revealed that while increasing the number of AGT genes in a mouse elevates blood pressure, similar manipulations to the number of ACE genes have no effect whatsoever on a mouse's blood pressure. Plugging such data into his customized computer program allows Dr. Smithies to ask -- and answer -- further questions about the effects of genetic and pharmacologic manipulations. ["Computers help decipher blood pressure control" National Institute of General Medical Sciences research brief, Mar. 31, 1999]  http://www.nigms.nih.gov/news/releases/smithies.html

We are investigating the hypothesis that essential hypertension, one of these diseases, is caused primarily by combinations of quantitative genetic variants that individually have only modest effects. To test this hypothesis we have developed a gene targeting approach which allows the level of expression of chosen genes to be varied systematically in different animals by varying the number of functional copies of the target gene from 1 through 4. We have applied this "gene titration" method to several genes in the renin- angiotensin system and in the natriuretic peptide system and we have shown that genetic changes which affect the level of expression of the genes coding for angiotensinogen (AGT), or for renin, or the type 1a receptor for angiotensin II (Atr1a), or the endothelial form of nitric oxide synthase (eNOS), or the atrial natriuretic factor (ANF) or its receptor (NPRA) all affect blood pressures in the mouse. [Oliver Smithies, Univ. of North Carolina- Chapel Hill, Lineberger Comprehensive Cancer Center, 2001] http://cancer.med.unc.edu/researchers/DisplayByList.asp?ID=178

gene trapping: Traditional gene- trapping approaches, in which genes are randomly disrupted with DNA elements inserted throughout the genome, have been used to generate large numbers of mutant organisms for genetic analysis. Recent modifications of gene- trapping methods and their increased use in mammalian systems are likely to result in a wealth of new information on gene function. [Durick K, et al. “Hunting with traps” Genome Research 9(11): 1019-1025. Nov. 1999]

genetic enhancement: Genetic & genomic testing

genetic engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [MeSH, 1989] 

Related term:  recombinant DNA technology. [IUPAC Compendium]

genetic recombination:  Production of new arrangements of genes by various mechanisms such as assortment and segregation, crossing over, gene conversion, transformation, conjugation, transduction, F-duction, or mixed infection of viruses. MeSH, 1968

Happens during the cell division (meiosis) that occurs during the formation of sperm and egg cells. In this process, chromosomes pair up and may swap portions of genetic material in a phenomenon known as crossing over. The chromosomes then reassemble and separate, with each containing some material from the other. The chromosomes are then divvied out into individual sex cells. During crossing over, it is more likely that far- apart genes will be separated by a break than those that are close together. The genes that tend to stay together are said to be linked and therefore may serve as markers for one another — a pattern that is of particular interest when, for example, one of the genes is a disease gene. 

Related terms: recombinant, recombination

genetic vector : Any DNA molecule capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from plasmids, bacteriophages or viruses. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain genetic markers to facilitate their selective recognition. MeSH, 1980

genomewide knockdowns:  RNAi is already making an impact. Genomewide knockdowns have been carried out in organisms including nematodes. Small interfering RNAs (siRNAs), which silence genes in mammalian cells, are now being designed against as many genes as possible. The RNA Revolution,  BioIT World April 2003 http://bioitworld.com/archive/041503/blueprint_sidebar_2305.html 

genomic library: A collection of clones made from a set of randomly generated overlapping DNA fragments representing the entire genome of an organism. [DOE] 

A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns). MeSH, 1990 

host: A cell whose metabolism is used for growth and reproduction of a virus, plasmid, or other form of foreign DNA.  [IUPAC Biotech]

host-vector system: A compatible combination of host (e.g. bacteria) and vector (e.g. plasmid) that allows propagation of DNA. [IUPAC Biotech]

hybridoma: A hybrid cell line resulting from the fusion of a specific antibody- producing spleen cell (lymphocyte) with a myeloma cell, which has the growth characteristics of the myeloma component and the antibody- secreting characteristics of the lymphocyte, and will multiply to become a source of pure monoclonal antibody. [IUPAC Biotech]

Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. MeSH, 1982

insertional mutagenesis: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene. This process may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. MeSH, 1991 

Enables researchers to both identify and sequence a gene, as well as get functional information about it. Is this related to gene trapping?

Does not require knowing gene's identity or function.

Related terms: embryonic lethal, knockdown

intrabodies: Recent advances in antibody engineering have now allowed the genes encoding antibodies to be manipulated so that the antigen binding domain can be expressed intracellularly. The specific and high- affinity binding properties of antibodies, combined with their ability to be stably expressed in precise intracellular locations inside mammalian cells, has provided a powerful new family of molecules for gene therapy applications. These intracellular antibodies are termed 'intrabodies'. [Wayne A. Marasco, "Intrabodies: turning the humoral immune system outside in for intracellular immunization" Gene Therapy 4 (1): 11- 15, Jan. 1997] 

knockdown: Altering the function of a gene so that it can be conditionally expressed. This is necessary when complete knockout of the gene would be lethal to the organism. 

Related terms: embryonic lethal trait, knockin, knockout; Pharmaceutical biology antisense; RNAI RNA Interference

knockin: Gain of function through addition/ substitution of genetic material. One example of a knockin is deletion of a coding sequence of a gene in a mouse and then replacing it with human coding sequences. 

Related terms: knockdown, knockout

knockout: Inactivation of specific genes. Knockouts are often created in laboratory organisms such as yeast or mice so that scientists can study the knockout organism as a model for a particular disease. [NHGRI] 

Narrower term: conditional knockout, random homozygous knockout Related terms gene knockout, knockdown, knockin, protein knockouts

knockout mice: Model & other organisms

Knockout-mouse technology is considered an essential and standard technique in functional genomics and target validation. 

lambda phage: See under bacteriophage

library: Combinatorial libraries & synthesis

How does this relate to combinatorial library and related terms in Drug discovery & development (or more general meanings of  "library").  

Narrower terms: gene library, genomic library;  Microarrays arrayed library; Sequencing DNA library 

molecular display: See under phage display

molecular evolution: The aims and scope statement of the Journal of Molecular Evolution states that topics addressed cover "experimental and theoretical work aimed at deciphering features of molecular evolution and the processes bearing on these features, from the initial formation of macromolecular systems onward, includ[ing] the evolution of informational macromolecules and their relation to more complex levels of biological organization, up to populations and taxa. This coverage accommodates well such subfields as comparative structural and functional genomics, population genetics, the molecular evolution of development, the evolution of gene regulation and  gene interaction networks, and in vitro evolution of DNA and RNA. Aims and Scope, Journal of Molecular Evolution, Springer] http://www.springeronline.com/sgw/cda/frontpage/0,11855,4-10027-70-1034044-detailsPage%253D...

Wikipedia http://en.wikipedia.org/wiki/Molecular_evolution 

Google = about 84,600 Aug. 20, 2003; about 440,000 Nov. 29, 2004

Narrower terms: applied molecular evolution; Proteomics  directed protein evolution   Related term: gene shuffling

molecular farming:  Related/equivalent? term: pharming

Google = about 17,800 Dec. 16, 2004; about 42,500 Jan 8, 2008

molecular systems biology: An integrative discipline that seeks to explain the properties and behaviour of complex biological systems in terms of their molecular components and their interactions.  Nature Publishing, Molecular Systems Biology aims & scope  http://www.nature.com/msb/authors/index.html#Aims-and-scope 

Broader term: systems biology

monoclonal antibodies MAbs:  Drug targets

mutagenesis: The introduction of permanent heritable changes (i.e., mutations) into the DNA of an organism. [IUPAC Bioinorganic] 

Mutation and gene disruption are powerful tools for investigating gene function and for identifying novel genes without prior knowledge of homology in other systems. Screening for phenotypes of interest leads to discovery of new genes, some of the mutations becoming models for human genetic diseases.  [Functional Genomics, UK "Analysis of phenotypic changes resulting from mutagenesis and gene disruption" 2001] http://www.functionalgenomics.org.uk/sections/programme/mutagenesis.htm

Narrower terms: chemical mutagenesis, insertional mutagenesis, saturation mutagenesis, site- directed mutagenesis. Broader terms: gene disruption, gene manipulation Related terms: knockouts, knockins, knockdowns

nuclear transfer: In nuclear transfer the DNA is removed from an unfertilised egg and the nucleus of a specially prepared body cell is introduced and the combination or "couplet" is triggered either by an electrical pulse, or the introduction of a chemical, to fuse them together and begin the process of development. Much is still to be known about what happens in this process and most attempts fail at the start.

At Roslin this has been achieved by inserting a treated cell inside the outer shell of the "empty" egg. Other groups report success in extracting the nucleus of the cell and inserting it into the egg.  Cloning & nuclear transfer: A short glossary, Mike McKeen,  Roslin Institute Online, Scotland, 1999  http://www.ri.bbsrc.ac.uk/library/research/cloning/glossary.html#clon

See also under enucleated

nucleome: -Omes & -omics

null mutation: SNPs & Genetic variations

parthenotes: The products of human parthenogenesis.  Eggs can divide on their own as though they had been fertilized by a sperm, then go on to develop into embryos and offspring. Rick Weiss, Parthenotes Expand the Debate on Stem Cells, Washington Post, Dec. 10, 2001 http://www.washingtonpost.com/ac2/wp-dyn/A18046-2001Dec9?language=printer 

Related terms: Stem cells

peptide aptamers: Engineered protein molecules selected from combinatorial libraries, [used] to dissect the function of specific genes and alleles, and to trace genetic pathways. [Roger Brent "Peptide aptamers" Molecular Sciences Institute, 1999] 

Broader term: aptamers 

phage: A virus for which the natural host is a bacterial cell. [DOE]

Used as a vector for cloning segments of DNA. [Schlindwein] 

Related terms: bacteriophage, phage display. 

phage display: Functional diversity and drug-like properties can be found from compound libraries using display methodologies.  The most favored methods are yeast and phage display, as they offer a way to efficiently generate, screen, and optimize new classes of drugs. PEGs Protein Engineering Summit May 2010,Boston MA  
  Phage & Yeast Display

The growth in the monoclonal and recombinant antibodies area has been made possible by methods to create peptide libraries by phage display and engineer properties to enable them to become protein therapeutics. The improvements in speed and throughput along with advances in manipulating properties such as multi-specificity, immunogenicity, and aggregation will lead to the next generation of therapeutic antibodies for the clinic.  Phage Display to development Therapeutic Antibodies PEGs Oct 2009 Hannover Germany

Use of genetically engineered phage to present peptides as segments of their native surface proteins. Peptide libraries may be produced by populations of phage with different gene sequences. IUPAC Combinatorial Chemistry

Broader term: display technologies  Related terms:  bacteriophage, biopanning, phage;  Labels, signaling & detection; Proteomics directed protein evolution  

pharming: Use of  transgenic animals to produce drugs in their milk, urine or eggs.  Transgenic plants can also be used. (Tobacco is said to be particularly amenable to this application).   Google = about 10,600 Sept. 19, 2002; about 11,100 Sept. 16, 2004

Related terms: Genomics crop genomics; Assays & screening  phenotypic screening

plasmid, plasmids: Extrachromosomal genetic element consisting generally of circular double- stranded DNA, which can replicate independently of chromosomal DNA.  Used as vectors for cloning DNA in bacteria or yeast host cells. [IUPAC Bioinorganic]. Autonomously replicating, extrachromosomal circular DNA molecules, distinct from the normal bacterial genome and nonessential for cell survival under nonselective conditions. Some plasmids are capable of integrating into the host genome. A number of artificially constructed plasmids are used as cloning vectors. [DOE] Any extrachromosomal hereditary determinant. Plasmids are self- replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. MeSH, 1978   

polyclonal antibodies: A mixed population of antibodies that recognize numerous epitopes. HIV Plus 9, June- July 2000 http://www.aidsinfonyc.org/hivplus/issue9/report/glossary.html

Post-Transcriptional Gene Silencing PTGS: Was initially considered a bizarre phenomenon limited to petunias and a few other plant species, is now one of the hottest topics in molecular biology (1). In the last few years, it has become clear that PTGS occurs in both plants and animals and has roles in viral defense and transposon silencing mechanisms. Perhaps most exciting, however, is the emerging use of PTGS and, in particular, RNA interference (RNAi) —  PTGS initiated by the introduction of double-stranded RNA (dsRNA) — as a tool to knock out expression of specific genes in a variety of organisms (reviewed in 1-3). Ambion, RNA Interference and Gene Silencing, 2002  http://www.ambion.com/techlib/hottopics/rnai/   

Narrower term RNAi; Broader term:  gene silencing process biology:   

protein knockouts: Our proteomics efforts are focused largely on developing new techniques to probe protein- protein interactions and to construct devices that allow one to monitor the levels and post- translational modification states of hundreds or even thousands of proteins simultaneously. A third major goal is to develop “protein knockout” methods that would allow researchers to rapidly develop reagents to block one or more functions of a newly discovered protein to facilitate studies of its role in cellular metabolism. [Thomas J. Kodadek, Internal Medicine and Molecular Biology, Univ. of Texas Southwestern Graduate Biomedical School, 2001]   http://www2.utsouthwestern.edu/gradschool/webrib/kodadek.htm  

Google = about  24 Sept. 18, 2002; about 89 Nov. 29, 2004; about 179 Nov. 10, 2006; about 253 June 18, 2007

protein shuffling: We also constructed a computational method to determine the locations of crossovers that lead to functional hybrid proteins during in vitro recombination. Borrowing a concept from the schema theory of genetic algorithms, our approach assumes that crossovers resulting in functional proteins are those that least disrupt structural integrity. ... This method can be used to predict sites for protein shuffling and to screen sequence databases to determine optimal sets of starting sequences for in vitro evolution by recombination. Stephen L. Mayo, Computational Protein Design, Cal Tech, Howard Hughes Medical Institute http://www.hhmi.org/research/investigators/mayo.html

Google = about 16 Sept. 8, 2003; about 30 Nov. 29, 2004; about 115 Nov. 10, 2006

quiescence:  This is the state in which all but the most basic functions of a cell or group of cells has stopped. This is usually a response to an unfavourable environment, such as one in which the food supply is low or absent. The cell becomes dormant until its surroundings are more favourable. In this state the genes that define the specialist function of a cell "switch off" making the cell suitable for nuclear transfer.  Cloning & nuclear transfer: A short glossary, Mike McKeen,  Roslin Institute Online, Scotland, 1999  http://www.ri.bbsrc.ac.uk/library/research/cloning/glossary.html#clon

Related terms: cloning, enucleated, nuclear transfer rDNA: See recombinant DNA

random homozygous knockout: A genetic approach to identify genes whose inactivation leads to loss of a particular cell function, this provides a practical way to identify and map genes throughout the genome based on their biological actions and roles in human diseases. The single step of gene discovery and function validation allows rapid identification of genes and their genetic pathways relevant to human diseases and determination of their potentials as therapeutic targets. Dr. Limin Li "Random homozygous knockout" 

recombinant antibodies: Drug targets

recombinant DNA, rDNA: Biologically active DNA which has been formed by the in vitro joining of  segments of DNA from different sources. It includes the recombination joint or edge of a heteroduplex region where two recombining DNA molecules are connected. MeSH, 1977 

recombinant DNA technology: A body of techniques for cutting apart and splicing together different pieces of DNA. When segments of foreign DNA are transferred into another cell or organism, the substance for which they code may be produced along with substances coded for by the native genetic material of the cell or organism. Thus, these cells become "factories" for the production of the protein coded for by the inserted DNA.  NIGMS

Related terms: biotechnology, genetic engineering; Cell biology clones, homologous recombination, vectors   

recombinant proteins:  Proteins prepared by recombinant DNA technology.  MeSH, 1986 

Related term: genetic recombination 

recombinant therapeutics: See recombinant antibodies, recombinant proteins recombination: The formation of new combinations and arrangements of genes during meiosis; recombination is achieved by crossing over, independent assortment, and segregation. NHLBI  

Can be natural or synthetic. Narrower term:  genetic recombination 

restriction endonucleases: Stuart Linn and Werner Arber [52] and Matthew Meselson and Robert Yuan [53] found specific restriction endonucleases in bacteria, which act when the latter defend themselves against the attack of bacteriophages; thus these enzymes restrict the host range of the bacteriophages. Harry Smith and K. W. Wilcox [54] were able to purify these enzymes, and Thomas Kelly and Hamilton Smith [55], Kathleen Danna and Daniel Nathans [56] and Philip Sharp et al. [57], determined their mode of action. These enzymes cut DNA molecules each at a specific site. These observations made it possible to isolate genes, to clone them and analyze their biochemical structure in great detail.  Following the action of restriction endonucleases, there often arise so- called cohesive ends in the DNA molecules [58], which tend to join together. By this means it is possible for example to join together DNA from any eukaryotic organism and that from the bacterial plasmids. Such recombinant DNA molecules were first constructed by David Jackson et al. [59], Peter Lobban and Armin Kaiser [60] and Stanley Cohen et al. [61]. Cloned DNA molecules can be physically mapped, using the cutting points of the restriction endonucleases as markers, [62] and sequenced by means of sophisticated biochemical methods [63, 64]. Petter Portin in "The Origin, Development and Present Status of the Concept of the Gene: A Short Historical Account of he Discoveries" Univ. of Turku, Finland, 2000 http://www.bentham.org/cg/sample/cg1-1/Portin.pdf

reverse chemical proteomics: Chemistry & Biology

reverse genetics: Going from a gene (or its DNA sequence), often discovered via high- throughput sequencing and bioinformatics technologies, to its biological function. Reverse genetic methods are much more amenable to whole genome, high- throughput analysis and to automation than is forward genetics. Contrast with forward genetics, in which one goes from a heritable phenotype to discovery of a gene and its function. 

Related term:  positional cloning   

reverse genomics: A genetic approach that has proved useful in discovering and characterizing mammalian genes that regulate cell proliferation and suppress tumorigenesis. In reverse genomics, scientists use "reporter genes," whose expression is controlled by DNA sequences linked to them, to investigate genetic regulatory mechanisms in both simple and higher organisms. Researchers can now directly isolate genes that specify functions of particular interest using reporter- gene- containing cassettes that can manipulate, as well as monitor, the expression of genes in mammalian chromosomes. [Stanley N. Cohen, Stanford Univ. "Manipulative Reporter Genes and "Reverse Genomics"  Joshua Lederberg Distinguished Lecture in Molecular Genetics, Rockefeller Univ. Oct. 27, 2000]  http://www.rockefeller.edu/lectures/cohen102700.html 

ribosome display:    

RNAi RNA interference: A gene silencing phenomenon whereby specific dsRNAs ( RNA, DOUBLE- STRANDED) trigger the degradation of homologous mRNA ( RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA- INDUCED SILENCING COMPLEX (RISC). DNA METHYLATION may also be triggered during this process. MeSH 2003  See also RNA

Narrower terms: miRNA, siRNA
Broader terms: gene expression regulation, gene silencing

Nature Reviews Focus on RNAi http://www.nature.com/focus/rnai/  

RNAi Consortium:  A public-private consortium based at the Broad will develop and validate tools and methods that will enable the worldwide scientific community to use RNAi to unveil the function of most human and mouse genes. The goal of the RNAi Consortium (abbreviated TRC) is to use the recently discovered RNAi mechanism to create widely applicable research reagents consisting of specific inhibitors against human and mouse genes.   http://www.broad.mit.edu/genome_bio/trc/  

RNAi therapeutics: RNAi for therapeutic indications, June 2009, San Francisco CA

RNA silencing: Although initially recognized as a handy tool to reduce gene expression, RNA silencing, triggered by double- stranded RNA molecules, is now recognized as a mechanism for cellular protection and cleansing: It defends the genome against molecular parasites such as viruses and transposons, while removing abundant but aberrant nonfunctional messenger RNAs. The underlying mechanisms in distinct gene silencing phenomena in different genetic systems, such as cosuppression in plants and RNAi in animals, are very similar. There are common RNA intermediates, and similar genes are required in RNA silencing pathways in protozoa, plants, fungi, and animals, thus indicating an ancient pathway.  Tijsterman M. et. al., The genetics of RNA silencing, Annual Reviews Genetics; 36: 489- 519, 2002   

Related term: RNAi RNA interference  

SELEX Systematic Evolution of Ligands by Exponential Enrichment: Process for identifying aptamers by iterative enrichment of  oligonucleotide mixtures with respect to their ability to bind a target.  [IUPAC COMBINATORIAL CHEMISTRY 

saturation mutagenesis: A technique to mutate all bases of a gene. [Glick]

second- site mutations: Are not lethal themselves, but in combination with the primary defect cause lethality.

Related term: synthetic lethal screening shuffling: Narrower terms: DNA shuffling, domain shuffling, exon shuffling, gene shuffling, protein shuffling

semantic systems biology: Semantic technologies are playing an increasingly important role in capturing and modeling biological knowledge. Semantic systems biology can complement the bottom-up approach with data-driven generation of hypotheses. Therefore, Semantic Systems Biology (SSB) is a systems biology approach that uses semantic description of knowledge about biological systems to facilitate integrated data analysis.  About Semantic Systems Biology http://www.semantic-systems-biology.org/about 

site-directed mutagenesis: The substitution or modification of a single amino acid at a defined location in a protein is performed by changing one or more base pairs in the DNA using recombinant DNA technology. [IUPAC Bioinorganic]

Mutagenesis where the mutation is caused by in vitro induction directed at a specific site in a DNA molecule. The most common method involves use of a chemically synthesized oligonucleotide mutant which can hybridize with the DNA target molecule. The resulting mismatch - carrying DNA duplex may then be transfected into a bacterial cell line and the mutant strands recovered. MeSH, 1991 

somatic cell hybridization:  In somatic cell hybridization, human cells and rodent tumor cells are fused (hybridized); over time, after the chromosomes mix, human chromosomes are preferentially lost from the hybrid cell until only one or a few remain. Those individual hybrid cells are then propagated and maintained as cell lines containing specific human chromosomes. Improvements to this technique have generated a number of hybrid cell lines, each with a specific single human chromosome. Primer in Molecular Genetics, Oak Ridge National Lab, US   http://www.ornl.gov/hgmis/publicat/primer/intro.html

synthetic lethal screening: Second- site mutations that are not lethal themselves, but in combination with the primary defect cause lethality. Used in yeast genetics, but can be generalized to model organisms other than yeast. The rationale is that many mutations commonly found in tumors that result in instability of the genome are loss- of- function mutations, and it is difficult to replace the function of missing or altered proteins with a small- molecule drug. The idea of screening for second- site mutations is to identify targets that when inhibited by a specific novel drug may specifically result in the death of cells that have such a loss- of- function mutation, but that will be nontoxic to normal cells. 

systems biology: This report focuses on the current and future applications of Systems Biology in drug discovery, specifically in pinpointing optimal individual targets, and combinations of targets, to overcome metabolic pathway redundancies, leading to efficacious and safe products. Insight Pharma Reports, Systems biology: A disruptive technology, 2008

The label “systems biology” is pretty awful, except, of course, for the many even worse labels that have been tried. More important is what SB seeks to do: transform biology and health care into a rigorous, predictive science offering a richer understanding of biology and a vastly improved approach to drug development and medicine. SB would build on the molecular biology revolution and elucidate the wiring diagrams (and their rules) buried in the data.   John Russell, BioIT World, Sept  2007 http://www.bio-itworld.com/issues/2007/sept/cover-story/ 

Systems biology is frequently defined as the study of all of the elements in a biological system and their relationship to one another in response to perturbation. Advances in science and technology are enabling the development of this emerging and cross-disciplinary field by allowing researchers to explore how biological components function as a network in cells, tissues and organisms. Recently, pharmaceutical companies have begun to embrace systems approaches in an effort to better understand physiology, pathogenic processes and pharmacological responses. This review focuses on recent advances within three core areas of systems biology: data collection, data analysis, and the integration and sharing of data.  Susie Stevens and J. Rung, Advances in systems biology: measurement, modeling and representation, Current Opinion in Drug Discovery and Development, 2006 Mar; 9(2): 240- 250.

Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. Instead of analyzing individual components or aspects of the organism, such as sugar metabolism or a cell nucleus, systems biologists focus on all the components and the interactions among them, all as part of one system. These interactions are ultimately responsible for an organism´s form and functions. Systems Biology, the 21st century science,  Institute for Systems Biology, Seattle, 2005 http://www.systemsbiology.org/Intro_to_ISB_and_Systems_Biology/Systems_Biology_--_the_21st_Century_Science 

There are two opinions on what systems biology is supposed to be. One group sees systems biology as another level of combining data from different levels (like DNA, RNA and protein level) (see [Leroy] HOOD). Another group wants to combine classical molecular and cell biology with systems theory and focus on the new forms of behavior that emerge when systems of genes and proteins are studied in a wholistic way. For this they need data from all those different levels as well, of course. That is why they see systems biology as a cooperative effort, with systems theory providing a theoretical framework and a new view on things for biologists, along with lots of experience with complex systems, and biology providing in-depth knowledge of the field of application as well as practical handling experience. This data is the basis for developing the kind of detailed models that are necessary for such studies of systemic properties and behavior. For both groups, the goal is to reach a new level of understanding of biological systems often referred to as 'systems level' understanding. A glossary for Systems Biology, Systems Biology Group, Stuttgart http://www.sysbio.de/projects/glossary/SYSTEMS_BIOLOGY.shtml#systems_biology    

The very nature of systems biology requires integrating data from a variety of sources generated and interpreted by people skilled in different areas --  engineering, computer science, biology, physics, mathematics, and statistics. Key considerations in this process include the generation of quantitative data, barriers in communication across departments, and organizational challenges.

Glossary for systems biology, Institutes for System Dynamics and Control and for Systems Theory in Engineering of the University of Stuttgart 100 + definitions, 2002 http://www.sysbio.de/projects/glossary/index.shtml  
What is systems biology? Institute for Systems Biology, Seattle WA http://www.systemsbiology.org/Default.aspx?pagename=whatissystemsbiology  

Google = about 865,000 May 25, 2005; about 1,530,000 Nov 10, 2006

Related terms: In silico & molecular modeling; Molecular Medicine: preventive medicine  Narrower terms: comparative systems biology, molecular systems biology; hepatocyte systems biology, semantic systems biology ;  In silico & molecular modeling applied systems biology, in silico biology ; Metabolic engineering signal transduction 
Pharmaceutical biology integrative biology- 

systems biology targeted mutation: A type of mutation in which a chromosomal gene is altered by the substitution of a DNA construct assembled in vitro. In mouse, the constructs are usually designed to eliminate gene function; such targeted mutations are often casually referred to as knock-outs. Some DNA constructs are designed to alter gene function; such targeted mutations are often casually referred to as knock- ins [Mouse Genome Informatics Glossary, Jackson Laboratories, US] http://www.informatics.jax.org/userdocs/glossary.shtml#synonym

transgenic: Model & other organisms

vector: 1. A DNA molecule (plasmid, virus, bacteriophage, artificial or cut DNA molecule) capable of being replicated and bearing cloning sites for the introduction of foreign DNA, used to introduce this DNA into host cells. 2. Any organism that transmits a disease between two hosts. IUPAC Biotechnology 

An agent, such as a virus or a small piece of DNA called a plasmid, that carries a modified or foreign gene. When used in gene therapy, a vector delivers the desired gene to a target cell. NHGRI 

The two different senses of the IUPAC definitions should be clear from context.  The organisms transmitting pathogens can be insects or small animals. Vectors used in gene therapy are not pathogenic.  

Narrower terms: BAC Bacterial Artificial Chromosome, cloning vector, genetic vector, plasmids

Vector databases see Databases & software directory 

Yeast Artificial Chromosomes YACS: Chromosomes in which fragments of exogenous DNA ranging in length up to several hundred kilobase pairs have been cloned into yeast through ligation to vector sequences. These artificial chromosomes are used extensively in molecular biology for the construction of comprehensive genomic libraries of higher organisms. MeSH, 2002

yeast display: See under phage display

Bibliography
RNAi Gateway, BioMedCentral, http://www.biomedcentral.com/gateways/rnai/ 
Systems Biology Gateway, BioMedCentral http://www.biomedcentral.com/gateways/systemsbiology/ 

Alpha glossary index
How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.