L11 : Drosophila Model System to Study Regulatory Networks

Question 1

Briefly overview Drosophila as model organism?

Answer 1

Drosophila melanogaster
Fruit fly

Question 2

Who was the first major researcher to use Drosophila as model organism?

Answer 2

Thomas Hunt Morgan
Explained sex linkage
In 1910 isolated first mutant fly with white eyes

Question 3

Advantage of Drosophila life cycle for research?

Answer 3

Short life cycle
About 10 days at 25°C and 28 days at 18°C

Rapid development allows for quick generation turnover in experiments

Question 4

Why is drosophila considered efficient for breeding in lab?

Answer 4

Breeds quickly
- Each female produces many progeny

Question 5

Describe maintenance and storage of drosophila in lab?

Answer 5

Inexpensive to maintain
- Can be stored in tubes or vials
- Fed simple diet of sugar, yeast, agar

Question 6

What are key reasons Drosophila is a good in vivo model compared to cell cultures?

Answer 6

Reflects complexity and structure of whole animals
- Cell cultures are artificial
Around 75% known human disease has counterpart in fruit flies

Question 7

What genetic tools make Drosophila a useful model organism?

Answer 7

Genetic tools
- Marked chromosomes
- Balancer chromosomes
- Naming via phenotype

Helps track mutation and preserves genetic lines

Question 8

What are balancer chromosomes?

Answer 8

Multiple inversions that prevent recombination with homologous chromosomes

Question 10

What is the UAS/GAL4 expression system?

Answer 10

Uses the GAL4 TF to bid upstream activation sequences (UAS) and drive gene expression

Question 11

How is the UAS/GAL4 system used in Drosophila?

Answer 11

Gene expression studies
- Used to selectively activate expression in specific tissues

Question 12

How does tissue-specific expression work using UAS/GAL4 system?

Answer 12

1. Fly line expressing GAL4 under tissue-specific promoter
2. Crossed with another line carrying UAS-human transgene
3. GAL4 activates transgene only in target tissue, enabling precise spatial control

Question 13

What genetic resources are available for Drosophila research?

Answer 13

FlyBase
Comprehensive database for Drosophila genetics
~13,000 annotated genes

Question 14

Describe an important difference between fly and mouse organs?

Answer 14

Mouse organs have ongoing cell division
Fly organs are mostly post-mitotic
- Fixed post development
- Except gut

Question 15

Describe use of Drosophila model system for circadian rhythm and sleep?

Answer 15

Flies that are inactive/sleeping will not interrupt infrared beam

Question 16

Describe use of Drosophila model organism for feeding?

Answer 16

FlyPAD setup allows monitoring of:
- Food preferences
- Feeding behaviour
- Nutritional needs

Question 17

What are examples of research using Drosophila model system?

Answer 17

Cancer
Genetics, chromosome mechanics
Evolution
Metabolism
Ageing
Neurodegenerative disease

Question 18

What are the parallels between embryonic and cancer development?

Answer 18

• Rapid division of cells
• Cell movement
• Differentiation

Question 19

What are the differences between normal development and cancer progression?

Answer 19

During normal development:
- Cells stop dividing when appropriate
- Correct differentiation

Question 20

Describe the use of Drosophila as a model for cancer?

Answer 20

Conservation of key signalling pathways that have been implicated in cancer eg.
- Notch
- Hippo
- Hedgehog/ Wingless

Question 21

Expand on what the Notch pathway is?

Answer 21

Conserved cell-cell communication system
Implicated in cancer
- Can act as oncogene or tumour suppressor depending on context

Question 22

Why is the Notch pathway researched in Drosophila?

Answer 22

1. Resemblance in domains and protein structure between flies and humans
   - Directly relevant
2. Only 1 Notch receptor in flies vs multiple homologues in mammals
   - Less complex to study

Question 23

How are tumour allografts used in Drosophila cancer research?

Answer 23

Involves injecting flies with tumours

Allows examination of how host environment influences tumour development and progression

Question 24

Describe the use of Drosophila as a model for studying innate immunity?

Answer 24

Lacks adaptive immunity, making it ideal to study innate immunity in isolation

Question 25

What is cell competition?

Answer 25

Occurs when, within growing tissue, stronger cell populations outcompete and eliminate weaker or less fit cells

Question 26

Describe the use of Drosophila as a model for studying cell competition?

Answer 26

Cell competition first discovered in Drosophila and only later in mammals Promotes tissue health by selecting for optimal cells

Question 27

Describe use of Drosophila as a model for drug screening?

Answer 27

Enables high throughput screening of potential anti-cancer drugs in living organism

Question 28

Explain example of Ross Cagan lab for Drosophila drug screening?

Answer 28

1. Drosophila larvae with induced brain tumours, do not reach adulthood 2. Placed into 96-well plates containing different drug compounds 3. Systematically tests effect of each on survival time

Question 29

Why is using Drosophila model advantageous over cell line studies?

Answer 29

- Evaluates drug effects in whole, complex organism - Can detect toxicity/side effects that may not be apparent in isolated cells

Question 30

What is important to note about effectiveness of cancer treatment?

Answer 30

Cancer is easier to target in early stages before multiple mutations accumulate Order and timing of drug treatment have significant effect

Question 31

Describe how Drosophila can be used as a model in cancer treatment?

Answer 31

Tumours from patients can be sequenced Creation of a genetically matching 'personlised fly avatar' Used to rapidly screen drug candidates Allows recommendation of personalised treatment regimens