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Undeleted > Systems biology > Flashcards

Systems biology Flashcards

1
Q

What is systems biology

A

The study to develop a quantitative understanding of biological systems.

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2
Q

What is a temporal reaction network

A

Gene or Biochemical networks.

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3
Q

What is the goal of systems biology

A

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

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4
Q

What is a network

A

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

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5
Q

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

A

E + S ES -> E + P

Where E = enzyme; S = substrate; P = product.

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6
Q

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

A

To work out the concentration change:

Minus anything that creates it; add up anything that uses it up.

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7
Q

What is the Michaelis Menten equation

A

v = Vmax[S] / Km + [S]

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

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8
Q

What are the two types of Hill function

A

Normal ‘Hill function’ - positive curve

Repressor Hill function - negative curve

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9
Q

Describe the process of negative auto regulation

A

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

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10
Q

Why is negative regulation important in cells

A

Prevents build up

Increases reaction rate

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11
Q

What is the difference between negative and positive auto-regulation

A

Neg is much faster
Pos is much slower
(than simple outside regulation)

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12
Q

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

A

Feed-forward loop

Feed-back loop (cycle)

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13
Q

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

A

8
4 - coherent
4 - incoherent

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14
Q

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

A

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

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15
Q

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

A

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.

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16
Q

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

A

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.

17
Q

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

A

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

18
Q

Give examples of a coherent type 1 feed-forward loop

A 
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)
19
Q

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

A

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.

20
Q

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

A

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

Increased rate of response.

21
Q

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

A

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).

22
Q

How can network responses (reactions) be sped up

A

Increased degradation rate
Use of Negative feedback
Use of Incoherent feed forward loop.

23
Q

What are the two types of movement a cell makes

A

Run (straight line)

Tumble (no movement, randomly changes direction)

24
Q

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

A

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

25
Q

How are the two types of cell movement achieved

A

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

26
Q

What is the Gierer-Meinhardt model for pattern formation

A

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.

27
Q

What are the two types of Gierer-Meinhardt diffusion

A

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.

28
Q

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

A

Chemotaxis signalling pathways in Dictyostelium.
Activator - PI3 kinase
Inhibitor - PTEN
They counteract each others cellular effects; and regulate.

29
Q

How can the chemotactic response be changed/amplified

A

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

30
Q

What dose LEGI stand for

A

Local activation-global inhibition

31
Q

Define chemotaxis

A

The movement of an organism in response to a chemical stimulus

32
Q

What are the two competing models for chemotaxis

A

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.

33
Q

How is a compass/LEGI mechanism involved in cell movement

A 
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.

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