Core Research Flashcards
Tissue bank
a collection of human tissue or other biological material, stored for potential research use beyond the life of a specific project with ethical approval
What is a HTA license (consent) required for?
any “scheduled purpose” involving removal, storage and use of human tissue, from the living or decease
- anatomical examination
- storage/use for public display
- research in connection with disorders of human body
- post mortem examinations, including removal and storage of tissue
Conditions where license/consent not required?
- tissue that is stored and used for NHS REC approved specified research projects (anonymised) (unspecified requires lisence)
- Storing organs for less than 24 hours prior to transplantation
Generic consent?
Broad consent given eg. donation to a tissue bank for storage/use for unspecified research bank
Proteome definition
the entire set of proteins expressed by a cell, tissue or organism
Central Dogma
an explanation of the FLOW of generic information within a biological system “DNA makes mRNA and mRNA makes protein”
miRNA
short, non coding RNA molecules that act as negative regulators of gene expression, by inhibiting mRNA translation or promoting mRNA degradation
Evidence Based Medicine
the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients
Bias
any influence that acts to make observed results non-representative of the true effect of therapy
Placebo effect
a response to a medical intervention that results from the act of carrying out the intervention itself, rather that from the specific treatment mechanism
Microsatellites
repetitive segments of DNA scattered throughout the genome in non coding regions. Used as markers of linkage analysis because of their naturally occurring high variability in repeat number between individuals
GWAS
OBSERVATIONAL study of a genome-wide set of genetic variants in different individuals to see if any variant is associated with a trait - determine what AREAS of the genome contribute to disease
Epigenetics
the study of heritable changes in gene EXPRESSION that do not involve changes to the underlying DNA sequence
Intervention
a set of planned actions that are designed to bring about desired changes (outcomes) in defined beneficiaries in order to address a health or social problem
Bradford Hill Criteria
group of principles that are used to establish epidemiological evidence of a causal relationship between a presumed cause and an observed effect
Bias
Any systematic error (in the research methodology) in an epidemiological study that results in an incorrect estimate of the association between exposure and risk of disease
Confounding
Possibility that an observed association is due to the effects of differences between the study groups (other than the exposure under investigation), that could affect the risk of developing the outcome being studied
Sanger Sequencing
To determine the DNA sequence of a shorter sequence of DNA (900 bp). Uses chemically altered, dyed ‘dideoxy’ bases to terminate newly synthesised DNA fragments at specific bases. The fragments are then separated by gel electrophoresis, and the modified didNTP bases can be detected as each one emits a light of a specific wavelength
Illumina Sequencing
Involves cleaving the DNA sample into short fragments, then cluster generator by ligating longer fragments to ‘adaptors’ and annealing to a slide using the adaptors.
Bridge PCR
Slide flooded with modified dNTPs (contain terminator) and DNA polymerase
Image taken of the slide at each read location - fluorescent signal which means that a picture of the DNA is built up base by base
NGS: sequencing reactions are constructed simultaneously on a large no of DNA fragments on a solid surface, fast and cheap
PCR
Used to amplify a specific fragment of DNA for analysis
- Denaturation -> separate strands
- Annealing -> cool so primers bind to complementary sequences
- Extension -> raise reaction temp so taq polymerase extends primers, creating new strands
- doubles each cycle 1,2,4,8*
Adv: speed, simplicity, low cost, can amplify a really small fragment, used in qt RT PCR, immunohistochemistry etc, don’t need to know DNA sequence
Disadv: primer can attach to wrong part if sequence appears more than once, doesn’t allow for localisation
Pre-clinical trial drug development
safety pharmacology, preliminary toxicological testing, pharmacokinetic testing, chemical + pharmaceutical development
drug discovery: natural sources, study of metabolites, molecular design, new disease insight
Phase 1 trial
initial administration of drug into humans 20-50 people, healthy volunteers determine tolerability of dose range Single ascending dose (SAD): PK Multiple ascending dose (MAD): PK, PD
NOAEL
MABEL
use lowest estimated dose with a safety margin, cautious increases in dose - steep dose response curve
drug administration: continuous monitoring, best clinical practice, preform in specialist clinical trials unit, prepared for adverse consequences, stringent stop criteria
Phase 2a trial
50-500 people (patients)
to test drug effectiveness
continuing safety evaluations
Phase 2b trial
assessment of dose ranging and dosing intervals - how well the drug works at the prescribed dose