1st week: 2

Question 1

What is studied with animal models? (6)

Answer 1

• A gene and its encoded protein (and different isoforms)
• how specific genes and proteins interact
• the signalling pathway and how it works
• the formation/ specification of cell types, tissues and organs
• the circuits and networks in the nervous system
• the above in relation to disease

Question 2

What are these phyla:

Chordata?

Arthropoda?

Answer 2

CHORDATA: animals in this category have notochords (not always a vertebrate). Frogs etc. also humans

ARTHROPODA: insects

HUMAN:

Kingdom: Animalia

Phylum: Chordata

Class: Mammalia

Order: Primates

Suborder: Haplorhini

Infraorder: Simiiformes

Family: Hominidae

Subfamily: Homininae

Tribe: Hominini

Genus: Homo
Linnaeus, 1758

Question 3

How far apart in evolution are humans to insects?

Answer 3

500 million years

Question 4

Why study animals?

Answer 4

Main reason:

understand causes, mechanisms, pathways from molecule to mind

Question 5

The relative position or connection in homologous parts; they may differ to almost any extent in form and size, and yet remain connected together in the same invariable order.

Darwin, 1876, p. 382

What is this principle?

Answer 5

Homology

Question 6

Example of what?

Answer 6

Homologous genes/proteins

Sequence identity between orthologous genes/proteins from different species

Question 7

Methods possible/used in animal studies:

Answer 7

• mutating, inactivating or overexpressing a gene/protein
• finding interacting/ binding partners
• screening for enhancers/ suppressors
  of ‘disease gene/protein’
• epistasis tests and manipulation of a signalling pathway
• targeted activation/ inactivation of neural circuits
• the regulation and function of behaviour

Question 8

What are these?

otd/Otx

unpg/Gbx2

Pax2/5/8

Hox1 orthologs

Answer 8

Genetic similarities between fly and mouse (and human)

Hirth & Reichert 1999

Question 9

Baker’s yeast has been used to discover …. and their function in the regulation of the cell cycle/cell division.

Answer 9

Baker’s yeast has been used to discover genes and their function in the regulation of the cell cycle/cell division.

Question 10

baker’s/brewer’s yeast is …cell

Answer 10

eukaryotic cell

Question 11

What is in the picture?

Answer 11

cell division of bakers yeast

Question 12

TDP-43and FUS genes has been discovered to be involved in the formation of …. disease.

Explain picture:

Glucose =

Galactose =

Answer 12

TDP-43 and FUS genes has been discovered to be involved in the formation of motor neuron disease.

TDP-43 and FUS inhibit the growth of yeast cultures, they build aggregates = they are toxic.

Glucose = gene has been turned off

Galactose = gene has been turned on

Question 13

What does FUS, TAF15 and TDB-43 do in yeast?

What is the importance in human disease?

Answer 13

Form aggregates, means they are toxic.

Couthouis et al. (2011)

In human postmortem samples it is visible that human homolog of TAF 15 also forms aggregates in ALS cases, which stands for amyotrophic lateral sclerosis.

Couthouis et al. (2011)

Question 14

What animal:

simple anatomy

959 somatic nuclei

302 neurons

transparent

small (1mm long)

250 progeny per generation

easily cultivated

eats bacteria

grown on agar plates seeded

with bacteria

rapid development (three days

life cycle at 25°C)

Answer 14

C. elegans

Question 15

Who got a Nobel Prize for finding out that C. Elegance has 959 cells

Answer 15

John Sulton 2002

Question 16

C. Elegance:

How many larval stages?

What is dauer?

Answer 16

L1 - L4

a stage where larva can survive for 4 months, doesn’t mature into an adult.

Question 17

daf-2 and daf-16 define …. in C. elegans

daf-2 and daf-16 affect each other in what way?

Answer 17

daf-2 and daf-16 define lifespan in C. elegans

Kenyon et al. (1993)

High levels of daf-2 causes the suppression of daf-16, which therefore are low, which leads to a normal lifespan, around 25 days.

daf-2 is low, it leads to the derepression of daf-16, which then leads to high levels of this protein, and that extends the lifespan. See image!!

Question 18

What’s the importance of daf-2, daf-16 and TOXO in humans?

Answer 18

daf-2 /IGF1 is insulin receptor in humans!

(Affects life span)

Gems & Partridge (2013)

Question 19

What animal?

• 180 Mb sequenced genome, 13,600 genes

(Compared to ~25,000 human genes)

• 65 per cent structural identity to human genes

Complex brain and behaviour, including learning and memory

• molecular, cellular and behavioural studies in vivo

Answer 19

Drosophila melanogaster

Question 20

What animal was first with fully mapped genome

Answer 20

Fruit fly, drosophila melanogaster

Question 21

Who studied chromosomes and inheritance using drosophila melanogaster?

When

Answer 21

1912

Thomas Hunt Morgan

Columbia University

Question 22

Drosophila melanogaster life cycle?

Answer 22

10-12 days

egg - larva - adult

Question 23

Drosophila transactivation tool, GAL4/UAS system.

Can be used as what?

Example

Answer 23

Enhancer in generating transgenic flies.

For example, as an enhancer that is specific for all the dopaminergic neurons.

When all the dopaminergic neurons are active, enhancer is transcriptionally active. It recognises the abstract activating sequence of a second set. That could for example be a green fluorescent protein.

Muqit & Feany (2002)

Question 24

What neuron circuit is studied in Drosophila melanogaster by Dr. Hirth?

Involved in what human activity?

Answer 24

Dopaminergic pathway

Voluntary movement.

Hirth (2010); Strausfeld & Hirth (2013)

Question 25

Genetic strings:

• forward genetics?
• reverse genetics?

Answer 25

Forward genetics:

Starting with a mutant phenotype, then identify the protein and the gene (Thomas Hunt Morgan)

Reverse genetics:

Knowing the (human) gene, then going to Drosophila, looked whether it has a human homolog, or a fly homolog in this case, and then we started to manipulate that gene, and then, we could look, how does that relate to the disease.

(picture on the slide wrong?)

Question 26

Behavioural phenotype caused by disease-related genes/proteins can be tested with Drosophila.

Give an example

(Hirth (2010))

Answer 26

Parkinson’s disease, introduced mitochondrial dysfunction in cholinergic, dopaminergic; and serotonergic neurons.

Question 27

What was the effect on mitochondrial dysfunction in cholinergic, dopaminergic; and serotonergic neurons?

Answer 27

Only affected dopaminergic.

Question 28

What does cell lineage mean?

Answer 28

All cells derive from one.

J. Sutton was able to trace this tree in C. Elegance, got a Nobel Price for it.