Lecture 15: Disease modelling & Drug Screening

Question 1

From healthy state to disease state =

Answer 1

• infectious agents
• geentics
• Iatrogenic disease (doctors)
• physical damage (e.g. radiation, chemicals)

Question 2

in relation to diseases we would like to

Answer 2

• prevent the disease occurring
• reverse the disease process
• • for this we need a TARGET for the drug to act on, & a drug must be discovered & developed + tested

Question 3

The drug discovery process =

Answer 3

• target identification
• lead selection
• lead optimisation
• pre-clinical development
• clinical phase 1
• clinical phase 2+ 3

Question 4

once u have some understanding of potential targets you can screen small molecules in either:

Answer 4

• conventional drug discovery pipelines

- using PSCs

Question 5

Why is it beneficial to model human diseases using human cell lines?

Answer 5

organisms (mouse+ humans) have differences:

• developmental
• physiological
• physical
• genetic

Question 6

what the issue in using human cell lines?

Answer 6

Patient derived cells can be useful BUT what if you want to study early stages of tumorigenesis?

Question 7

human pluripotent stem cells: 3 major advantages over conventional cell lines?

Answer 7

1) Normal, primary cell line
2) Grow indefinitely
3) Differentiate to any cellular fate

Question 8

Penetrance =

Answer 8

the proportion of individuals with a specific genotype who express a particular phenotype

Question 9

How are iPS + ES cells similar but different

Answer 9

both pluripotent BUT iPS cells carry the genotype of the parent cells. (could make iPS cells from different genotypes, inc. those with diseases)

Question 10

by comparing patient iPS cells & ‘Normal’ iPS cells we can

Answer 10

look in the lab and try to discover the underlying mechanism

Question 11

what other cell shave iPS cells been derived from?

Answer 11

• epidermis
• neuron
• blood
• beta-cell
• • in reality it appears any cell can be reprogrammed to an iPS cells

Question 12

Several diseases have now been modelled &tested with drugs:

Answer 12

• Cardiac
• Schizophrenia
• Alzheimer’s disease
• Early-onset Alzheimers
• Retinitis pigmentosa

Question 13

Testing drugs for embryo toxicology:

Answer 13

• If you can measure the production of cells that represent these different stages - and QUANTIFY
• you could screen for any deviation from ‘normal’
• if there were any deviations these cpds may be teratogenic

Question 14

whats used to cause myotube formation (fusion)

Answer 14

horse serum