A few definitions
|Any small organism (commonly used in reference to a bacterium, but can also refer to fungi, algae or amoebae )
|A particle of genetic material surrounded by a protein coat and other structures which can infect animal or bacterial cells and cause this cell to produce more copies of viral genetic material and structures. It cannot replicate without a host.
|A single-celled organism, found everywhere. Huge variation in types, structures and behaviour. The vast majority live as colonisers or commensals on our skin, mouth, respiratory tract and gut, and are essential for healthy bodily function. Occasionally they become ‘pathogenic’ or harmful – where they cause a severe infection.
The micro-organisms we work on
|A bacterium which can cause severe gastrointestinal infections, commonly called a ‘hospital superbug’ as it is much more common in people who have been treated in hospital. It appears to colonise the gut of many healthy humans, especially toddlers, and even adults, but in certain conditions (e.g. when antibiotics have wiped out all the other bacteria in the gut) it can lead to overgrowth of the bacteria and can produce toxins which cause severe infection.
|Our group is aiming to find out how it is transmitted between patients, and what causes some strains of C. diff. to cause severe infection.
|A bacterium which commonly colonises our skin, nose and respiratory tract. However, it can also cause severe infection if it gets to the wrong place.
Methicillin-sensitive Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus—the same bacterium, but it has a gene which makes it resistant to many of our common antibiotics (penicillins). It can also colonise patients or cause severe infection, which will then be harder to treat.
|Our group is looking into how both MSSA and MRSA are transmitted in hospitals and intensive care units by examining the genetics of strains found on skin, hospital surfaces, and healthcare workers which cause infection.
|Group A streptococcus
(e.g. Strep. pyogenese.g. Strep.agalactiae)
Group B streptococcus
(e.g. Strep. agalactiae)
|Group A streptococci are bacteria which can cause throat infections (such as strep throat) and, more rarely, skin infections and rheumatic fever. Many people are colonised with group A strep without symptoms.
Group B streptococci are bacteria which can cause pneumonia and meningitis, especially in newborns.
|Our group is studying why some strains appear to cause severe infection, and how the introduction of streptococcal vaccinations are altering the streptococcus infections.
Usually referring to:
|Tuberculosis is a lung condition caused by infection by a particular type of bacteria (the mycobacteria) and causes a severe illness which is often very difficult to treat.
The most common cause is the bacterium Mycobacterium tuberculosis, but it can also be caused by bacteria such as Mycobacterium bovis, M. africanum, or M. canetti (many clinicians will use the term TB when they mean MTB and vice versa—it is very confusing)
|Our group is studying how genome sequencing can be used to track how and when TB is transmitted, and how it can be used to predict resistance to treatment.
Klebsiella pneumonia/Klebsiella oxytoca
|A group of bacteria which commonly colonise our gut.
A bacteria which colonises our gut skin, and sometimes our urinary tract, but can also cause severe infection. It has the ability to transfer genetic material easily between different E. coli strains, and even other bacterial species, enabling it to pick up antibiotic resistance very easily.
Another common gut organism, which can also transfer genetic material and resistance easily. Together with E. coli it is one of the bacteria which is becoming resistant to antibiotics most quickly.
|Our group is studying how antibiotic resistance genes convey resistance and how it is transmitted, and how we can potentially prevent the bacteria becoming resistant.
DNA sequencing terms
|The entire genetic material of an organism
|A single piece of DNA. Humans have 47 different chromosomes. Bacteria have one chromosome which contains the bulk of their genetic material .
|A molecule that encodes the genetic instructions used in development and functioning of all known living organisms and many viruses.
|Small circles of DNA which contain genes and can be transmitted between bacteria. One bacterium can contain many of these in addition to its chromosome.
|Small fragments of DNA which can insert themselves into plasmids or chromosomes, and transmit between bacteria.
|Mobile Genetic Element
|Any genetic material which can be transmitted between different bacteria.
|The sequence of DNA which encodes a protein
|Sequencing all the DNA that is present in a sample (rather than an individual bacteria that has been cultured on an agarose plate)
|One nucleotide on a strand of DNA, also called one base.
A base pair = the base with its complementary pair on the other strand of the DNA double helix.
|Single Nucleotide Variant
|A difference between two DNA strands of one nucleotide (/base).
|Single Nucleotide Polymorphism
|Insertion or deletion mutation
|An entire sequence of DNA is either inserted or deleted into the DNA sequence
|The similarity of a sequence. A homologous sequence is the same. Two sequences with high sequence homology are very similar.
|Vertical gene transfer
|Genetic material is inherited from a parent cell
Programs and techniques we use to construct and analyse genomes using computers
|Pulsed Field Gel Electrophoresis
|Identification technique—uses fragments of DNA and identifies similarity in the pattern of DNA fragments to draw conclusions as to how similar they are (e.g. tuberculosis uses a technique called MIRU-VNTR).
|Multi-Locus Sequence Typing
|Identification technique—small parts of DNA from the genome (at particular locations or ‘loci’) are sequenced and compared (e.g. SPA –typing for Staph. aureus: ‘ST’ = Sequence Type (as identified by this technique)).
|Whole Genome Sequencing
|The entire genome (rather than just parts of it) are sequenced>
|This involves sequencing the genome one nucleotide at a time. It was the first method pioneered that allowed whole-genome sequencing, but is much slower than new techniques
|This refers to a number of techniques which allow ‘high throughput’ sequencing where entire genomes can be sequenced in hours to days.
|Shotgun sequencing/Short read sequencing
|This involves breaking the entire genome into fragments,(around 150-300 nucleotides long) and sequencing these fragments all at the same time. This makes sequencing long pieces of DNA much faster, but the DNA sequence then needs to be reassembled using complex computer algorithm. As of 2002-2017 this is the cheapest, most widely used type of whole-genome sequencing.
|Long read sequencing
|A long sequence of DNA is sequenced together, so computer re-assembly programs are not needed. This is potentially very useful, but the technology is developing and quite expensive.
|A company that make DNA sequencers like the MinION and GridION, which do long read sequencing quickly and cheaply, on small portable devices. As of 2017 the accuracy is not as high as other technologies but is improving. https://nanoporetech.com/
|PacBio make long-read DNA sequencing technology using a technique they call Single Molecule Real Time Sequencing (SMRT). It is much more accurate than other technologies as isn’t reliant on error-prone computer assembly algorithms, but is much more expensive as of 2017. http://www.pacb.com/smrt-science/smrt-sequencing/
|Illumina are a company that make widely-used short-read DNA sequencing machines such as the HiSeq and MiSeq https://www.illumina.com/
A few more DNA sequencing terms
|A small fragment of DNA which has been sequenced.
|A number of small fragments which all ‘fit’ together to create a longer sequence (contiguous sequence)
|De novo assembly
|A technique where fragments of DNA are all assembled together to create a genome ‘from new’
|Fragments of DNA are compared with a known ‘reference genome’, and fragments with the same sequence as a part of the reference gene are ‘mapped’ or ‘aligned’ to this part. The genome is then assembled.
Coverage = how much of the reference gene/genome has fragments which map to it.
|Basic Locus Alignment Search Tool
|A sequence of DNA is compared with a database of known sequences, enabling us to find out what genetic material is in our sample.