Glossary
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
A
Adaptor proteins: A protein that acts as a connecting molecule. An adapter protein is critical to intermolecular interactions and plays a role in the regulation of signal transduction initiated by engagement of surface receptors on all cell types.
Albumin: The most abundant protein important for transporting fatty acids, thyroid hormones some steroid hormones and other substances.
Antigen: A substance that stimulates an immune response, especially the production of antibodies. Antigens are usually proteins or polysaccharides, but can be any type of molecule, including small molecules (haptens) coupled to a carrier-protein.
Anti-TNF: A new class of drugs available for the treatment of severe rheumatoid arthritis.
B
C
c-fms: the gene that encodes the receptor for the major macrophage growth factor, CSF-1.
Candidate targets: A gene or gene product; expressed either specifically in macrophages from diseased tissue, or during stages of differentiation or activation of animal or human macrophages in vitro or in vivo; assessed for face validity (eg. distinction from non druggable targets such as housekeeping genes) and novelty.
Cartilage: A dense type of connective tissue found in joints.
Chromatin: A complex of DNA and protein found inside the nuclei of cells.
COPD: a group of destructive inflammatory lung diseases.
COX2: An enzyme responsible for formation of mediators which cause inflammation and pain.
Cre: an enzyme useful in conditional targeting.
CSF-1: one of the most important macrophage specific growth, survival and activation factors. CSF-1 works by activating the CSF-1 receptor encoded by the gene c-fms.
Cytokines: Small secreted proteins, which mediate and regulate immunity, inflammation and hematopoiesis. They are produced de novo in response to an immune stimulus.
D
E
Embryonic stem cells: Stem cells derived from embryos that develop from eggs that have been fertilized in vitro in an in vitro fertilization clinic and then donated for research purposes with informed consent of the donors.
Emphysema:Is characterized by loss of elasticity of the lung tissue; destruction of structures supporting the alveoli; and destruction of capillaries feeding the alveoli. The result is that the small airways collapse during expiration, leading to an obstructive form of lung disease where air is trapped in the lungs.
Endotoxin: Part of the outer membrane of the cell wall of Gram-negative bacteria. The biological activity of endotoxin is associated with the lipopolysaccharide (LPS).
Ets1 & Ets2: Ets1 and Ets2 are nuclear phosphoproteins which bind to DNA in vitro and share two domains of strong identity.
F
Fibrin: A protein involved in the clotting of blood.
Flow cytometry: A method that uses fluorescent dyes to measure the pattern of proteins expressed on the surface of a cell. Flow cytometry can also be used to isolate cells from complex cell mixtures based on this pattern and can be adapted to study signalling and other events inside the cell.
G
Gene expression: The process by which a gene's DNA sequence is converted into the structures and functions of a cell.
Gene microarrays: Glass slides with thousands of genes spotted in a geometric grid, are used with fluorescent dyes to determine the pattern of gene expression in a diseased cell or tissue.
Gene modification: A set of methods to turn on or turn off genes in cells, tissues or whole animals, especially mice. Gene modification is one of the cornerstones of modern biotechnology and medical research as it allows gene function to be studied in biological systems and disease models.
Gene transcription:The transferring of genetic information from DNA to RNA beginning the process of translating the genetic code into functional peptides or proteins.
Glucocorticoids: A class of steriod hormones characterised by an ability to bind to the cortisol receptor and trigger similar effects.
GM-CSF: A blood cell growth factor that is also strongly implicated in inflammation.
H
Homeostasis: The property of an open system, especially living organisms, to regulate its internal environment to maintain a stable, constant condition, by means of multiple dynamic equilibrium adjustments, controlled by interrelated regulatory mechanisms.
Hypoxic:A lack of oxygen.
I
Integrins:Integral membrane proteins in the plasma membrane of cells. They play a role in the attachment of a cell to the extracellular matrix (ECM) and in signal transduction from the ECM to the cell.
Intra-articular:The point of articulation between two or more bones, especially a connection that allows motion.
Intracellular vesicles: Vesicles within a cell.
IFNAR1 and IFNAR2: the two subunits of the cell-surface receptor for type I interferons.
In vitro: A study that is carried out in isolation from a living organism.
In vivo: A study that takes places within a living biological organism.
J
K
Knock out: a type of gene modification where a gene is inactivated. Knock out mice lack functional copies of the gene of interest. Recent refinements allow for controlled knockouts (conditional and tissue specific modification) and the insertion of altered but functional versions of genes (knock-ins).
L
Leucine Rich Repeats (LRR):short amino acid sequence motifs that are rich in leucine residues and primarily function to mediate physical interactions between proteins.
Lipopolysaccharide (LPS): a major component of the outer wall of Gram-negative bacteria and a potent activator of macrophages.
M
‘MacBlue’ mice:Mice that express Cyan Fluorescent Protein in monocytes and macrophages.
‘MacGreen’ mice:Mice that express Green Fluorescent Protein in monocytes and macrophage.
Macrophage:A defensive cell type found in all tissues of the body that can cause disease if its phenotype is altered leading to inappropriate growth survival or activation.
mBSA/IL-1 arthritis:An experimental model of arthritis triggered in mice using mBSA (methylated Bovine Serum Albumin) protein and the inflammatory cytokine, IL-1.
Mesenchymal stem cells: Or marrow stromal cells (MSC) are multipotent progenitor cells that can differentiate into a variety of cell types.
Messenger RNA (mRNA):The macromolecule used by cells to carry genetic codes to the enzymatic machinery in the cell that makes proteins.
Micro-fluidic card:An assay system that allows high throughput gene expression studies to be performed at a fraction of the usual time and cost.
Monocytes: Are a leukocyte (type of white blood cell), part of the human body's immune system that protects against blood-borne pathogens and moves quickly to sites of infection in the tissues.
Murine arthritis: Mice with arthritis
Myeloid cells: Referring to the non-lymphocytic groups of white blood cells, including the granulocytes, monocytes and platelets.
N
O
Oligonucleotides: Short nucleic acid sequences of up to about 20 nucleotides.
Orthologue: A homologous sequence found in different species and derived from a common ancestor.
Osteoarthritis: A condition involving the breakdown of the protective cushion of the cartilage covering the ends of the bones where two bones meet to form a joint.
Osteoblast: A cell that makes bone.
Osteoclast: A bone specific macrophage which responsible reabsorbs bone.
Osteoclastogenesis: The process whereby osteoclasts are formed through the interaction of bone marrow stromal cells with haematopoietic osteoclast precursors.
Oxidative stress genes: Genes induced during times of increased oxidative burden (i.e. exposure to cigarettes) and are responsible for detoxifying harmful oxidants such as super oxides and peroxynitrite derivatives that are abundant constituents of cigarette smoke.
P
Pathogen: Or infectious agent, is a biological agent that causes disease or illness to its host.
Pathogenesis: The mechanism by which a certain aetiological factor causes disease.
Perioxisome Proliferator-Activated Receptors (PPARs): Regulate gene expression and are involved in regulating glucose and lipid metabolism as well as having anti-inflammatory functions.
Peritonitis Model:A mouse model used to test antibiotics in vivo before moving to larger animals or humans.
Phagocytic:Cells that ingest or engulf other cells or particles. The phagocyte may be a free-living one-celled organism or one of the body cells.
Phenotype: The functional form of a cell, tissue or animal. Changes in phenotype are characteristically accompanied by alterations in surface proteins identifiable by flow cytometry, changes in activation state, and in whole animals, altered susceptibility to disease.
Plasminogen: An important enzyme that degrades many blood plasma proteins, most notably fibrinclots.
Plasma membrane: Or cell membrane is a selectively permeable bilayer which comprises the outer layer of a cell.
Pluripotency: Exhibiting a capacity to produce several distinct biological responses.
Polymerase Chain Reaction (PCR): A molecular biology technique for enzymatically replicating DNA or RNA.
Progenitor cells: Precursor cells from which a cell lineage arises.
Proliferation: Cell growth.
Protein Kinases: Enzymes that modify other proteins by chemically adding phosphate groups to them (phosphyorlation). This usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins.
Proteomics: A group of technologies employed to isolate and characterise proteins, including rare disease causing proteins. Modern proteomics allows a protein’s gene code to be inferred by working backwards from the sequence of protein building blocks called amino acids.
Q
R
Reactive Oxygen Species (ROS): Includes oxygenions, free radicals and peroxides both inorganic and organic. They are generally very small molecules and are highly reactive due to the presence of unpaired valence shell electrons.
Real-Time or Quantitative PCR (QPCR): Allows quantification of starting amounts of DNA, cDNA, or RNA templates. QPCR is based on the detection of a fluorescent reporter molecule that increases as PCR product accumulates with each cycle of amplification.
Rheumatoid Arthritis: An ‘auto-immune’ disease, that is, a disease where a person’s immune system attacks his or her own body tissues. This auto-immune reaction causes inflammation of the joints, particularly of the synovial membrane which lines them. There is an over-production of synovial (joint) fluid and this, combined with the inflammation, causes joints to become swollen and painful.
Ribonucleic acid (RNA): A nucleic acid polymer consisting of nucleotide monomers. RNA nucleotides contain ribose rings and uracil unlike deoxyribonucleic acid (DNA), which contains deoxyribose and thymine. It is transcribed from DNA by enzymes called RNA polymerases and serves as the template for translation of genes into proteins.
RNA interference (RNAi): Refers to the introduction of homologous double stranded RNA (dsRNA) to specifically target a gene's product, preventing its function.
S
Scaffolding proteins: Proteins with docking sites which allow the formation of multimeric signalling complexes.
Schlafen genes: The Schlafen family of genes is differentially regulated during thymocyte maturation and is preferentially expressed in the lymphoid tissues.
SELDI-TOF MS: Corresponds to a modified mass spectrometer known as Surface Enhanced Laser Desorbtion Ionisation - Mass Spectrometer. It is typically used in conjunction with Ciphergens Protein Chip arrays to screen for novel proteins in complex biological mixtures.
Serum: The liquid component of blood with clotting factors removed.
Signal transduction pathways: A receptor is found in the membrane of the cell, a series of signals must be passed through the membrane to intercellular molecules which in turn activate transcription. This series of signals is called a signal transduction pathway.
Suicide gene: Insertion of a gene that orders particular cells to self-destruct.
Super antigen: An antigen that interacts with the T cell receptor in a domain outside of the antigen recognition site. This type of interaction induces the activation of larger numbers of T cells compared to antigens that are presented in the antigen recognition site.
Synovial Tissue: The lining tissue of joints that is attacked and destroyed progressively in RA.
Synovium: the lining tissue of joints that is attacked and destroyed progressively in RA.
T
TOF/TOF (Time of Flight/Time of Flight) instruments:is a component of a specialized mass spectrometer that can identify individual proteins by generating direct amino acid sequence information.
Toll-like receptors:Type I transmembraneproteins that serve as a key part of the innate immune system
Transcriptional elements:The region of a gene that regulates the expression of a gene.
Transfection: A set of techniques employed to artificially introduce genes into cells or tissues. Transfection is usually employed to study the functional effects of the protein encoded by the transfected gene.
Transgenic:An animal that carries a foreign gene that has been deliberately inserted into its genome.
Transgenesis: Consists of introducing an exogenous gene - called a transgene - into a living organism so that the organism will exhibit a new property and transmit that property to its offspring.
TRAP: Tartrate resistant acid phosphatase - an osteoclast-specific phosphatase that is used as a marker of osteoclast differentiation.
Type I interferons: A family of homologous cytokines (interferon-alpha and interferon-beta) that potently elicit an antiviral and anti-proliferative state in cells.
U
V
Validated target: A candidate target present (mRNA and protein) in diseased tissue therapeutically relevant (e.g. by antisense, antibody knockdown, dominant negative) in vitro, preferably in primary cells and with preliminary HTS assay configuration work completed; the existence of known polymorphisms of the protein and its differential expression in human or animal tissues to have been considered preferably determined.
W
Wild type:One of the major genotypes of a species that occur in nature by evolution.
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