Case Unit 7: Hypothesis free science

Question 1

What is hypothesis free science?

Answer 1

Not all ‘good’ science requires a strict hypothesis
Drugs can be designed without knowing the target
Trial lots of drugs and see which ones work

Question 2

How might a hypothesis be generated?

Answer 2

Observational studies e.g. case reports

Question 3

What is an assay?

Answer 3

Used to test of the pharmacological activity of a compound, to see if it works
Typically first step in drug discovery

Question 4

What is a screen?

Answer 4

The interpretation of the results of a large number of assays, to evaluate the activity of a library of compounds

Question 5

What is ‘deep learning’?

Answer 5

Artificial intelligence can be used to analyse images by learning what images show

Question 6

What are therapeutic antibodies?

Answer 6

Antibodies that have been designed for a specific target antigen e.g. a cytokine, lower it’s effect

Question 7

Which part of an antibody can be modified?

Answer 7

The Fab region (fragment antigen-binding)

Question 8

What is rational drug design?

Answer 8

Creating a drug with a specific shape and charge to match a target

Question 9

What are the advantages of the screening approach to drug discovery as opposed to rational drug design?

Answer 9

Nature has lots of molecules created already, may be a useful molecule that can be found there instead of creating one

Question 10

What is in vitro evolution of antibody fragments used for?

Answer 10

A method for producing a therapeutic antibody with very high affinity for it’s target

Question 11

How is in vitro evolution of antibody fragments carried out?

Answer 11

1. Synthesise many different genes for Fab region of antibody region
2. Fuse the Fab cDNA to the gene for a phage coat protein
3. Inserted both genes into vector
4. Vectors inserted into bacteriophages
5. Phages express Fab protein on surface
6. Apply phages to antigen - only ones with high affinity stick
7. Wash away any unbound
8. Use the high affinity phages to infect bacteria
9. Phages replicate, will mutate slightly
10. Expose phages to antigen again
11. Repeat cycle until you find a super high affinity binder

Question 12

What are aptamers?

Answer 12

A piece of single stranded nucleic acid that folds into a 3D structure and binds to a target complex
Used instead of therapeutic antibodies