HIRI focuses on RNA-based infection research. But what exactly is RNA? Or what, for example, is mRNA, which is being used in some of the COVID-19 vaccines?
These and many more technical terms from our research will be explained in the glossary.
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Antimicrobials stop or slow the spread of microorganisms. Alongside antiseptics and biocides, anti-infectives are a class of anti-microbials. More specifically, the term anti-infectives refers to a group of medicines that either prevent or treat infections from bacteria, viruses and fungi. They encompass antibacterial, antiviral and antifungal medications. A well-known example of an antibacterial is penicillin.
Antisense oligonucleotides/RNA antibiotics
Antisense oligonucleotides are small, synthetic, single-stranded nucleic acids that can be used to target specific regions of both nuclear and cytoplasmic RNAs. These molecules are able to alter RNA, and reduce, restore or modify the expression of proteins, offering great therapeutic potential. If programmed accordingly, antisense oligonucleotides can be used as a form of RNA antibiotics. This would allow for the targeting of antibiotic resistant pathogens, as an alternative to standard antibiotics.
The term Bayesian statistics refers to a statistical theory that views probabilities as quantifying belief.
Cell-free transcription-translation systems
The term cell-free transcription-translation systems refers to a cell lysate that can perform transcription and translation when DNA constructs are added. These systems, generally called TXTL, are used to perform rapid biochemical assays in small volumes without the challenges of protein purification or culturing cells, accelerating the pace of scientific discovery.
CLIP-Seq is short for cross-linking immunoprecipitation-high-throughput sequencing. It refers to a method used to identify which RNA types interact with each other or with specific RNA-binding proteins.
Commensal bacteria are bacteria that colonize tracts of a human or animal host without posing any harm or threat.
The abbreviation CRISPR is short for: Clustered Regularly Interspaced Short Palindromic Repeats. It refers to a specific group of repeating sequences within the genetic code of certain prokaryotic organisms such as bacteria and archaea. These sequences are associated to the cell’s immune system.
CRISPR-Cas is a prokaryotic immune system that scientists have harnessed as a genetic engineering tool. CRISPR-Cas technology involves two components that allow scientists to target and edit specific segments of DNA from animals, plants and microorganisms. The system requires a ‘guide’ RNA that allows scientists to target a specific DNA region while Cas, a nuclease guided by the RNA, cuts the DNA like scissors. Once the DNA is cut, it is then easy to rewrite the code, omitting or including specific sequences.
CRISPRi screen is short for CRISPR interference screen, a highly sensitive tool that allows scientists to study reduced gene expression.
Deep sequencing is a Next Generation sequencing technique that analyses a specific genomic region multiple times, this can be hundreds or thousands of times. This technique allows scientists to search for cells, microbes, or rare clonal types that represent less than 1% of a biological sample. For this reason, it can be used by researchers to identify pathogens present in a host sample.
Differential RNA-Seq is a high-throughput screening technique used to examine whether an mRNA molecule is a primary or a processed transcript.
Dual RNA sequencing is a technique that allows the analysis of genes from two different cells simultaneously, for example those of a host and pathogen. This technique can be used to study the entire infection process and the interactions between the two cells.
Gene fitness is a quantification of the contribution of a gene product to survival in a given condition.
Gene regulation is the regulation of gene expression by a cell, using a broad range of mechanisms, to increase or decrease the production of specific gene products (protein or RNA).
A genetic locus is a specific, fixed position on a chromosome where a particular gene or DNA sequence is located.
Genome editing is a type of genetic engineering, whereby DNA segments are inserted, deleted or modified at a specific location of a cell’s genetic sequence.
The term Grad-Seq refers to a technique called RNA gradient profiling by sequencing. This technique allows scientists to analyze the coding and non-coding segments of an RNA transcript. Grad-Seq enables the study of specific functional RNA classes, as well as important RNA binding proteins and their interactions.
High-throughput, genome-wide chemical probing technologies
High-throughput, genome-wide chemical probing technologies are tools and methods used to investigate the numerous RNA structures and functions across an entire genome.
In vitro models
In vitro models are experiments performed with microorganisms, cells or biological molecules outside of their normal biological context. These are usually carried out in labware such as test tubes, petri dishes, flasks and microtitre plates.
Library screening refers to the process of testing large libraries of DNA sequences and constructs can provide an immense volume of data with a single experiment. Scientists perform library screening to quickly learn about the rules for target selection by CRISPR-Cas systems and probe the genetics of different organisms across the entire genome.
Long non-coding RNA is a class of regulatory RNA that can influence chromosome structure, transcription, splicing, messenger RNA stability and availability. They can also contribute to post-transcriptional modifications.
Machine learning is a branch of artificial intelligence that seeks to develop applications that can autonomously learn from data and improve their pattern recognition and prediction accuracy over time. Algorithms, a sequence of statistical programming steps, are ‘trained’ to find patterns in large data sets to make decisions and predictions based on new data. In science, deep-learning algorithms can take raw features from very large, annotated data sets, such as a collection of genomes, and use this information to extract knowledge and create predictive tools based on patterns within the data.
Mass spectrometry is an analytical method used for determining the mass of charged atoms or molecules. For this purpose, the particles are ionised and then separated (e.g. by magnets) according to their mass-to-charge ratio. This method is used to study biomolecules and identify chemical identity or structure. Since the data obtained in this way can be easily digitised, mass spectrometers are increasingly coupled directly with computers.
The term microbiota refers to a specific group of microorganisms (bacteria, viruses, fungi and archaea) that populate a given environment. The human body is densely populated with microorganisms, especially the respiratory, urogenital and gastrointestinal tracts. The human microbiota can be affected by a series of factors, such as the diet and the use of antibiotics. The delicate equilibrium of this population of microorganisms within the human body can significantly influence health, with the potential for both protective and harmful effects.
The microenvironment is the immediate environment of a cell or tissue comprised of extra cellular matrix, cells and interstitial fluid. The microenvironment influences cellular phenotype through physical, mechanical and biochemical mechanisms.
Mutation based functional screen
Mutation based functional screens, also known as mutational interference mapping experiments (MIME), are used to identify at single-nucleotide resolution the primary sequence and secondary structures of an RNA molecule that are crucial for its function. MIME is based on random mutagenesis of the RNA target followed by functional selection and next-generation sequencing.
Next Generation sequencing
Next Generation sequencing, also known as high throughput sequencing, refers to various modern sequencing technologies. These techniques identify the nucleotide order of DNA or RNA transcripts and quantify them. They allow for much cheaper and quicker sequencing than previous techniques, and have revolutionized the study of genomics and molecular biology.
Non-coding RNA/Regulatory RNA
Non-coding RNA refers to a group of RNA molecules derived from non-coding genes that do not encode proteins, but possess other specialized cellular and molecular functions. This means they do not undergo translation, like messenger RNA, but rather remain active as RNA molecules within the cell. These molecules play an important role in regulating how genes are expressed (turned on and off) and are thus also known as regulatory RNAs. They are involved in regulating gene transcription and translation, post-transcriptional modifications and epigenetic regulation.
Organoids are organ-like microstructures that can be cultivated in a nutrient medium from stem cells and organise themselves into different, specialised tissues. In this way, it has already been possible to create models for the brain, heart, kidney, stomach and intestine. Although organoids do not correspond to whole organs in size and complexity, they offer an excellent opportunity to research diseases and their treatment.
A pseudoknot is an RNA structure caused by the twisting and folding of the RNA strand due chemical interactions within the molecule. These interactions can result in very complex and stable RNA structures. Due to variations in the spatial arrangements and interactions of the loops and folds, great structural diversity exists between different pseudoknots. These structures possess a variety of functions, playing a pivotal role in the alteration of gene-expression by inducing ribosomal frameshifting in many viruses.
Ribosomal frameshifting is a process whereby translation is essentially “recoded”. This means that in a given messenger RNA template, the code can be read in alternative ways. This phenomenon occurs without actually changing the code sequence, but simply by initiating the reading process (frame) from a different starting point. As the nucleotides of the messenger RNA are read in groups of three (codons), altering the reading frame, alters how the entire sequence is decoded. The result, is the ability to produce more than one protein from a single messenger RNA strand. This mechanism is often used by viruses.
A ribosome is a cell organelle that functions as a protein factory, where the translation of messenger RNA occurs. Several ribosomes can be attached to a single messenger RNA strand during translation. A mammalian cell can possess as many as 10 million ribosomes.
Ribo-Seq is a method based on RNA sequencing that allows scientists to obtain a global "snapshot" of all ribosomes actively translating within a cell at a given moment. This technique can identify the location of translation start sites on an mRNA molecule, and provide insights into the synthesis of peptides and proteins.
RNA (ribonucleic acid) is a compound involved in gene expression and cellular protein synthesis, in certain viruses it can also replace DNA (deoxyribonucleic acid) as a carrier of genetic information. Like DNA, it is composed of different repeating units called nucleotides that encode information. The units that make up RNA are: adenosine, cytosine, guanosine and uridine.
Messenger RNA carries the instructions in the form of a code that are necessary to build proteins during translation, it is classified as coding RNA. Other types of RNA possesses structural, catalytic and regulatory functions, these are classified as non-coding RNA. Examples of non-coding RNA include transport RNA, ribosomal RNA, small RNA and long noncoding RNA.
RNA antisense purification
RNA antisense purification is a biochemical purification method that enables the identification of the DNA, RNA or proteins associated with an RNA of interest.
RNA-binding proteins perform a critical role in the regulation of both transcriptional and posttranscriptional gene expression. These proteins can regulate the splicing process, as well as the transport, translation and decay of messenger RNA. They are essential for the stabilization and destabilization of messenger RNA in response to its surrounding environment.
RNA metabolic labelling
RNA metabolic labelling is a technique that provides invaluable insights into the history of a cell. The method is based on the incorporation of modified ribonucleosides into nascent RNA transcripts during proliferation of the cell.
Single-cell RNA-sequencing is a genomic analysis technique used for the detection and quantification of RNA molecules in a single cell. It allows scientists to study a specific cell, e.g. a pathogen, to investigate regulatory relationships between genes and provides a valuable insight into the development of cell lineages. This approach is important for investigating and understanding cell responses in a detailed and individualized way.
Before an mRNA molecule leaves the cell nucleus for protein biosynthesis in eukaryotes, it is processed. It receives a "cap" (5′-cap structure) at one end and a poly-A tail of adenine nucleotides at the other end. Both structures protect the mRNA and help with translation. In addition, there is the splicing process, in which the introns are removed from the mRNA and the remaining exons are joined together.
RNA-Seq is a technique that uses next-generation sequencing to identify the quantity and nucleotide sequences of RNA in a sample at a given moment. This can be used, for example, to obtain information on gene expression and post-transcriptional modifications. New methods of RNA sequencing are single cell sequencing and dual RNA-seq.
Small RNAs are a class of regulatory RNAs that play a fundamental role in post transcriptional regulation of gene expression. These molecules can control the stability and regulation of messenger RNA and contribute towards epigenetic modifications.
Splicing is the process by which the non-coding segments of genes, called introns, are removed from the original messenger RNA. This leaves behind only the coding segments, called exons, which are then rejoined to one another. The splicing process creates a mature messenger RNA template that is ready for protein synthesis.
Synthetic biology is a multidisciplinary field of research that involves redesigning or adapting biological parts or systems for useful purposes by engineering them to have new properties. This can be achieved by creating new systems or redesigning existing ones.
The term transcriptome refers to all the genes in a cell that have been actively transcribed from DNA into RNA. This can be both coding and non-coding RNA. In transcriptomics, the transcriptome is studied in order to understand gene expression more precisely.
Transcriptomics is the study of all the RNA molecules within a cell, also known as the transcriptome. Whilst many studies in transcriptomics focus on messenger RNA that code for proteins, a vast part of the RNAs within a cell are non-coding and possess a regulatory role instead. Spatial transcriptomics allows scientists to measure and map the specific location of gene activity within a cell or tissue sample.
Translation is the process of creating proteins from a messenger RNA template. This occurs within the ribosome, where the nucleotide sequence from the template is read. Reading is a highly controlled process, the nucleotides are read in a specific direction in triplets, known as codons. Each codon is translated into its corresponding amino acid. In this way a chain of amino acids in a specific order, dictated by the messenger RNA template, is synthesized to form a protein.
Transposon mutagenesis is a technique to randomly inactivate genes through the introduction of a selfish DNA element that can move itself to different locations in the genome.
Virions are virus particles that are located outside the cell. They contain nucleic acids (DNA or RNA) and are usually enclosed by a protein capsule and sometimes by a biomembrane. Lacking their own metabolism, virions have to penetrate cells in order to be able to reproduce and become viruses.
Virulence refers to the extent of pathogenicity of a pathogenic strain.