L15: Systems Biology

Question 1

define systems biology

Answer 1

• the study of complex interactions within biological systems
• it describes the network properties in a qualitative and predictive manner
• it is an integrative or holistic approach (rather than reductionistic)
• facilitated by modern large-scale DNA-sequencing and proteomics technologies

Question 2

what are regulatory circuits

Answer 2

simple networks consisting of nodes and edges

Question 3

regulatory circuits - nodes and edges

Answer 3

• node: gene (represented as a dot)
• edge: regulation of gene by the product of another (shown by a line)

Question 4

regulatory circuits - explain the arrows

Answer 4

• ->-: shows relationship but not the type
• –|: repressor
• –>: activator

Question 5

regulatory circuits - what is autoregulation

Answer 5

• can have two types:
  1. negative autoregulatory circuit
  2. positive autoregulatory circuit

Question 6

regulatory circuits: autoregulation - negative aurtoregulatory circuit

Answer 6

• a gene for a repressor is negatively controlled by its own product
• its a homeostasis mechanism

Question 7

regulatory circuits: negative aurtoregulatory circuit - how is it a homeostasis mechanism?

Answer 7

• it ensures that the protein level is held constant
• when the protein levels fall, gene expression increases
• when the protein levels increase, the gene expression is subdued

Question 8

regulatory circuits: autoregulation - positive aurtoregulatory circuit

Answer 8

• an activator protein stimulates the expression of its own gene
• results in slow accumulation of the protein product

Question 9

autoregulation: positive aurtoregulatory circuit - why does it result in slow accumulation?

Answer 9

gene expression of the protein product depends on the accumulation of the activator

Question 10

what are feed-forward loops

Answer 10

• when transcription factor A controls the gene for a second transcription factor B
• both A and B control a third gene C

Question 11

feed-forward loops - diagram

Answer 11

• it looks like a triangle
• one side of the triangle: A ->- B ->- C
• other side of the triangle: A -> C

Question 12

feed-forward loops: diagram - label the arrows

Answer 12

• A ->- B: indirect
• A ->- C: direct edge
• B ->- C: edge

Question 13

feed-forward loops - coherent motif

Answer 13

• both direct and indirect pathways to output (C) have the same effect
• A -> B -> C
• A -> C

Question 14

feed-forward loops - incoherent motif

Answer 14

• direct and indirect pathways have different effects
• A -> B -| C
• A -> C

Question 15

feed-forward loops - how does it relate to Drosophila dorsalventral patterning?

Answer 15

• Dorsal activates Twist; both factors activate Snail (coherent feed-forward loop)
• Dorsal activates Snail; other genes are activated by Dorsal but repressed by Snail (incoherent feed-forward loop)

Question 16

feed-forward loops: dorsalventral patterning - coherent feed-forward loop

Answer 16

• Dorsal –> Twist –> Snail
• Dorsal –> Snail

Question 17

feed-forward loops: dorsalventral patterning - incoherent feed-forward loop

Answer 17

• Dorsal –> Snail –| Other genes
• Dorsal –> Other genes

Question 18

what are oscillating circuits?

Answer 18

• expression of genes is periodically up-regulated and then down-regulated at regular intervals of time
• ex: circadian clock

Question 19

what are oscillating circuits - circadian clock

Answer 19

• it drives expression of large numbers of genes at different times during the day/night cycle
• the animal circadian clock is driven by a negative feedback loop involving activators Clock and Cycle and the repressor Period

Question 20

oscillating circuits - explain how the animal circadian clock works

Answer 20

• Clock and Cycle activate Period
• Period accumulates to critical levels and counteracts Clock and Cycle to shut off its own synthesis
• the Period protein is ultimately degraded, freeing Clock and Cycle to activate Period gene expression
• this regulatory cycle helps define the 24hr periodicity of the circadian clock

Question 21

what is the Repressilator?

Answer 21

• a synthetic circuit created in E. coli
• a circular three node network where all signs are negative
• it generates an oscillatory pattern of transcription with a periodicity of 2hrs
• oscillations are far less robust than natural systems
• the synthetic circuit has not fully mimicked the more intricate circuitry of natural oscillators

Question 22

what is the Repressilator? - explain the gene layout

Answer 22

• A –| B –| C –| A
• lambda P-R –> lac1
• P-LtetO-1 –> lambda cI
• P-LlacO-1 –> tetR