Research Glossary
Amino Acid
The individual building blocks of proteins. There are 20 amino acids that are naturally incorporated into proteins. The specific order of the amino acids determines the structure and function of a protein.
Antisense Oligonucleotide
Short piece of DNA or RNA with a precise sequence of nucleotides (DNA/RNA building blocks) that can specifically bind to messenger RNA (mRNA) of choice, which can in turn affect the expression of the gene from which the mRNA was produced.
Atrophy
The wasting of a part of the body. SMA is called spinal muscular atrophy because the lower motor neurons within the spinal cord degenerate, which leads to the wasting of skeletal muscles.
Autonomic Nervous System (ANS)
Forming part of the peripheral nervous system (PNS), the ANS acts to unconsciously control the function of internal organs. The ANS is involved in the regulation of heart rate, respiration rate, digestion, and perspiration amongst other things.
Autosomal Recessive
A form of inheritance meaning that a disease affects both males and females equally and that two faulty copies of a gene, one from each parent, must come together for the disease to occur. A disease is autosomal when the abnormal gene is found on one of the 22 non-sex chromosomes (autosomes), i.e. not on the X or Y chromosome.
Axon
The long, slender projections of a nerve cell that carry electrical impulses away from the cell body (where the nucleus resides) to its target such as the muscle.
Biomarker
Medical biomarkers are biological indicators that can be objectively measured to inform us of the progress of a particular disease, pathogenic process or response to therapeutic intervention. For example, the amount of a particular protein found in a blood or urine sample may have a strong correlation with the phase of a disease; measuring the amount of this protein would then allow us to assess the severity and state of the disease. Therefore, reliable biomarkers can also help to determine whether drugs are having the desired positive effect on a disease, as the biomarkers should be responsive to effective treatments.
Cardiac
Of or related to the heart.
Carrier
Somebody who inherits a faulty copy of a gene from one parent yet is symptomless due to the presence of one normal copy of that gene from the other parent. Carriers usually fail to show any disease symptoms, but can pass on their faulty gene and carrier status to their children.
Cell
The basic building block of life. A group of cells can work together with a common function to form a tissue. Cells come in many different forms such a motor neurons (a type of nerve cell), keratinocytes (main cell type of the skin), or erythrocytes (red blood cells).
Cell Culture
The process of growing cells obtained from a multicellular organism (including humans) in Petri dishes under controlled conditions in the laboratory. Cells can be manipulated to study mechanisms and processes involved in disease and test potential therapies.
Cell Line
A culture of cells derived from a single source. The established cells possess the same genetic makeup (i.e. are clones) and the ability to proliferate indefinitely.
Central Nervous System (CNS)
The brain and spinal cord.
Chromosome
Found within the nucleus of the cell, chromosomes are thread-like structures of DNA that are tightly coiled up around proteins and contain many different genes. Humans have 46 chromosomes per cell - 23 from each parent - except for the sperm and egg cells which possess just the 23. The number of chromosomes can differ between species, for instance, chimpanzees possess 48, dogs 78, and the platypus 52.
Denervation
The degeneration of nerve cells such that they no longer contact and excite their target muscle.
Distal
Anatomical term of location meaning situated away from the centre of the body. Distal muscles, such as those found in the legs and arms, are less affected by SMA compared to proximal muscles.
DNA
Deoxyribonucleic acid (DNA) is the molecule that contains the genetic instruction manual to build all known organisms. Short stretches of DNA sequence that code this information are known as genes. DNA consists of nucleotides, the specific sequence of which determines the properties of the proteins made from the genes. Within cells, DNA is organised into structures called chromosomes.
Drosophila
A type of fruit fly that is frequently used as a model organism to study biological processes. Drosophila melanogaster is the full Latin name of the most widely used fly.
Embryonic Stem Cell
A cell that is derived from a blastocyst (an early stage embryo) and that can be differentiated into a large number of different cell types.
Exon
See Splicing.
Gene
A stretch of DNA sequence that carries the information to produce a specific protein. Genes are the unit of heredity that are passed from one generation to the next. We usually possess two copies of each gene, one inherited from each of our parents. When genes are altered through mutation, this can affect the structure and function of the proteins that they produce, leading to disease.
Gene (Replacement) Therapy
A method for altering, removing or adding genetic material (DNA) to correct particular defective genes that are responsible for the development genetic disorders. Viruses are often used as delivery vessels.
Genome
The full set of genes found within an organism.
Glial Cell
A type of cell found within and that supports the nervous system. They play a role in supplying nutrients, maintaining neuronal architecture, transmitting electrical signals, and removing waste products, amongst other things.
Heredity
The passing of traits through the inheritance of genes from one generation to the next.
Induced Pluripotent Stem Cell (iPSC)
A cell (e.g. skin cell) that has been altered or “reprogrammed” by the expression of specific genes to become able to potentially differentiate into a number of different cell types, for instance a motor neuron.
Intron
See Splicing.
Messenger RNA (mRNA)
An intermediate molecule between DNA (genes) and proteins, serving as a template that can be read by the ribosomes to produce proteins (click here for more information).
Mitochondria
Distinct structure found within cells often referred to as the powerhouses as they generate most of the cell’s energy supply.
Motor Function/Performance
The ability to coordinate and carry out successful movement.
Motor Neuron
The nerve cells that connect the brain and spinal cord to skeletal muscles allowing conscious movement. They act as a message delivery system: electrical signals originating in the brain are fired down the spinal cord along ‘upper motor neurons’ and on to skeletal muscles via the ‘lower motor neurons’. Lower motor neurons are the main cell type affected by SMA.
Mouse Model
Strain/breed of mouse used to model and investigate human disease. Model mice are inbred so as to have the same genetic background in which to study the effects of mutations in genes known to cause disease in humans. SMA mice are used to learn more about the molecular and cellular processes underlying disease symptoms and to test potential therapeutics before translation in to human clinical trials.
Mutation
A permanent change in the DNA sequence of a gene that can be inherited by subsequent generations. Dependent upon where a mutation occurs within the gene, it can have no effect on the protein produced, or can disturb the protein's function causing a genetic disorder such as SMA.
Nerve Cell
Also called neurons, nerve cells are electrically excitable cells that allow the quick transmission of signals throughout the body. Different types of nerve cell make up the nervous system, which functions to allow us to respond and react to our surroundings.
Neuromuscular Junction (NMJ)
A specialised synapse between lower motor neurons and skeletal muscles that allows the passage of signals from the nerves resulting in contraction of the muscle.
Neuron
A nerve cell.
Nucleotide
The individual building block of our DNA and RNA. DNA consists of the nucleotides adenine (A), cytosine (C), guanine (G) and thymine (T). Within DNA, A pairs with T, and C with G. When paired up like this, nucleotides may also be referred to as base pairs.
Nucleus
The control centre of a cell that contains the DNA wrapped up within chromosomes.
Outcome Measure
A gauge of physical ability along a numerical scale that can be used to determine patient improvement or decline over time.
Pathology
The anatomical and/or functional consequences of a disease, i.e. the deviation from a healthy condition caused by disease.
Peripheral Nervous System (PNS)
Consists of the nerve cells found outside of the central nervous system (CNS). The PNS acts to connect the CNS with the muscles and internal organs. The lower motor neuron axons and their connections with the muscle (neuromuscular junctions) are found within the PNS.
Pharmacokinetics
The study of the fate of substances, such as drugs and chemicals, externally administered to a living organism. This includes analysing the rate at which a substance takes effect, the mechanisms of absorption and distribution throughout the body, and the duration of effect.
Protein
Consisting of chains of amino acids arranged in very specific orders, proteins are fundamental components of living cells that are required for the structure, function, and regulation of cells, tissues and organs. The order of amino acids within a chain is determined by the genetic code (DNA). Proteins possess unique functions within a cell, and examples include enzymes, hormones, antibodies and the survival motor neuron (SMN) protein.
Proximal
Anatomical term of location meaning situated close to the centre of the body. Proximal muscles, such as those found in the chest, are more affected by SMA than distal muscles.
Ribosome
Molecular machine that can read mRNA and use it as a template to produce protein with specific amino acids corresponding to the genetic information encoded by the DNA.
Sensory Neuron
The nerve cells responsible for converting external stimuli (e.g. sound, light, smell) from the environment into internal signals.
Skeletal Muscle
Consciously controlled muscle that attaches to bones allowing movement. Examples include the biceps, triceps, and thighs.
Splicing
Before mRNA can be read by ribosomes to produce protein, it must first be modified by the sticking, or “splicing”, together of important regions of the mRNA called exons, which encode important information about the protein. Exons are interspersed by regions of mRNA called introns that do not contain information necessary to build a protein. These introns are removed by the process of splicing (click here for a more detailed explanation of splicing that includes a picture).
Survival Motor Neuron 1 (SMN1)
The gene that when mutated leads to the development of SMA. SMN1 produces the SMN protein, which we need a certain level of in order for our lower motor neurons to survive and thrive.
Survival Motor Neuron 2 (SMN2)
The gene that can modulate the severity of SMA due to it being able to produce a small amount of functional SMN protein. The more copies of SMN2 that someone has, the more functional SMN protein they can produce. Patients with more severe forms of SMA (Type I/II) usually have fewer copies of the SMN2 gene than patients with Type III SMA.
Survival Motor Neuron (SMN) Protein
Produced from both the SMN1 and SMN2 genes, the SMN protein is required for the survival of lower motor neurons. Complete absence of SMN is deadly to all different types of cell, but at low levels, the lower motor neurons appear to be the most severely affected cell type.
Synapse
The region between a nerve cell and another cell (this can be a nerve cell or a different type of cell, for example a muscle cell) that permits the passage of electrical or chemical signals.
Systemic
Refers to something that is spread throughout the whole body.
Tissue
A collection of cells that work together to perform a common function. Organs are formed from multiple tissues working together with a common function.
Transcription
The process whereby information in the DNA sequence is converted to messenger RNA (mRNA) form before being translated into protein by ribosomes.
Translation
The process allowing the production of proteins from messenger RNA (mRNA) by ribosomes.
Translational Research
The conversion of knowledge gained in the laboratory using cell and animal models of disease into studies in humans.
Transgene
A gene or genetic material transferred from one species to another. This can occur naturally or through genetic engineering.
Vasculature
The network of blood vessels, including the arteries, veins and capillaries, found within a particular organ or part of the body.
