Systems biology

Question 1

What is systems biology

Answer 1

The study to develop a quantitative understanding of biological systems.

Question 2

What is a temporal reaction network

Answer 2

Gene or Biochemical networks.

Question 3

What is the goal of systems biology

Answer 3

To develop a quantitative understanding of the biological function of genetic and biochemical networks

Question 4

What is a network

Answer 4

How things relate to other things (in a biological context; how gene X relates to gene Y etc)

Question 5

What is Michaelis Menten kinetics (AKA lass of mass action)

Answer 5

E + S ES -> E + PWhere E = enzyme; S = substrate; P = product.

Question 6

How can the Michaelis Menten equation be used to work out the concentration change of an enzyme/substrate/product

Answer 6

To work out the concentration change:Minus anything that creates it; add up anything that uses it up.

Question 7

What is the Michaelis Menten equation

Answer 7

v = Vmax[S] / Km + [S]where Km = Kr+Kcat / Kf ; and Vmaz = Kcat[C]o

Question 8

What are the two types of Hill function

Answer 8

Normal ‘Hill function’ - positive curveRepressor Hill function - negative curve

Question 9

Describe the process of negative auto regulation

Answer 9

The product of transcription acts as a repressor of the transcription reaction.

Question 10

Why is negative regulation important in cells

Answer 10

Prevents build upIncreases reaction rate

Question 11

What is the difference between negative and positive auto-regulation

Answer 11

Neg is much fasterPos is much slower(than simple outside regulation)

Question 12

What are the two classes of loops that exist when 3 interactions are involved

Answer 12

Feed-forward loopFeed-back loop (cycle)

Question 13

How many types of feed-forward loop exist (3 interactions)

Answer 13

84 - coherent4 - incoherent

Question 14

What is the difference between coherent and incoherent feed-forward loops

Answer 14

Coherent - no change in sign. No contradicting stimulation/inhibitionsIncoherent - change of sign. Contradictions present.

Question 15

What are the two most common types of feed-forward loop

Answer 15

Coherent type 1 - All stimulated. X stimulates both, but X and Y are both needed to stimulate Z.Incoherent type 1 - X stimulates Y and Z; but Y inhibits Z.

Question 16

What does the graph look like for a coherent type 1 feed-forward loop

Answer 16

All stimulate. X and Y both needed to stimulate Z. X is produced. Y concentration slowly increases. When it reaches an appropriate level, Z concentration increases. The delay is referred to as Ton.This has no effect on the ‘off’ response.

Question 17

What is the benefit of a coherent type 1 feed-forward loop

Answer 17

Filters out small perturbations.X can randomly briefly activate, however Y does not reach the required concentration to activate Z (unless genuine stimulation).

Question 18

Give examples of a coherent type 1 feed-forward loop

Answer 18

ARA locus (genes use/transport arabinose). cAMP stimulates CRP (X); arabinose stimulates AraC (Y); they both stimulate araBAD/araFGH (which is able to stimulate Y).Time delay in production, but rate is about the same as a simple regulatory loop (lacZ locus used as simple comparison)

Question 19

What does the graph look like for an incoherent type 1 feed-forward loop

Answer 19

X stimulates Y and Z. Y inhibits Z. Results in ‘pulses’. X stimulated. Causes increases in Y and Z concentrations. When Y hits a certain concentration (Kyz), concentrations of Z decrease. Rate of decrease depends on the Repression strength (F) of gene Y.

Question 20

What is the benefit of an incoherent type 1 feed-forward loop

Answer 20

There is only a brief increase in levels of Z gene. Increased rate of response.

Question 21

Give an example of an incoherent type 1 feed-forward loop

Answer 21

Galactose system in E.coli.cAMP stimulates CRP production (X).This stimulates GalS (Y) and galETK (Z) production.GalS is a negative autoregulator, and inhibted by galactose (and inhibits galETK production).

Question 22

How can network responses (reactions) be sped up

Answer 22

Increased degradation rateUse of Negative feedbackUse of Incoherent feed forward loop.

Question 23

What are the two types of movement a cell makes

Answer 23

Run (straight line)Tumble (no movement, randomly changes direction)

Question 24

What is the difference between a random walk and a biased random walk

Answer 24

Biased is semi-directional - random movements, but will tend toward a higher concentration. Random has no tendency.

Question 25

How are the two types of cell movement achieved

Answer 25

Movement of the flagellar. Can move clockwise or anticlockwise. This determines whether the cell ‘runs’ or ‘tumbles’.

Question 26

What is the Gierer-Meinhardt model for pattern formation

Answer 26

Patterns are formed by 2 substances; an autocatalytic activator (activates itself and an inhibitor), and an inhibitor (long range)(prevents unlimited activation).Depending on distance between activator and inhibitor, the same process can yield a varying result - hence patterning.

Question 27

What are the two types of Gierer-Meinhardt diffusion

Answer 27

Either the activator OR the inhibitor diffuses faster.If inhibitor diffuses faster; activator is only active for a short time, inhibitor (long range) catches up, activator is stopped.If activator diffuses faster; inhibitor ‘chases’ activator. Activator is able to propagate, but is eventually halted when the inhibitor catches up/gets lapped.

Question 28

Give an example of the Gierer-Meinhardt model for pattern formation

Answer 28

Chemotaxis signalling pathways in Dictyostelium.Activator - PI3 kinaseInhibitor - PTENThey counteract each others cellular effects; and regulate.

Question 29

How can the chemotactic response be changed/amplified

Answer 29

GPCRs - non-adaptive; cannot be changedWhen GPCR is activated, causes creation of RasGEF and RasGAP (Incoherent feed-forward loop) - adaptiveThe result of RAS is stimulation of PI3K, which activates PIP3/PTEN. Signal amplified.

Question 30

What dose LEGI stand for

Answer 30

Local activation-global inhibition

Question 31

Define chemotaxis

Answer 31

The movement of an organism in response to a chemical stimulus

Question 32

What are the two competing models for chemotaxis

Answer 32

Cell is migrating. 1, Compass/LEGI mechanism:Stimulus reorientates compass. Compass causes formation of new pseudopod. Cell turns towards stimulus.2, Pseudopod-centred mechanism:Pseudopods form at random. Pseudopods grow at different rates depending on stimuli present. Pseudopod without stimulus is withdrawn. Leads to gradual turns, in a stimulus bias direction.

Question 33

How is a compass/LEGI mechanism involved in cell movement

Answer 33

Pseudopods generated at random. Compass autocatalyses (activator); amplifies and localises spatial information. If stimulus is present, new pseudopod created at site of signal amplification. Cell is steered towards signal.