Systems biology Flashcards
What is systems biology
The study to develop a quantitative understanding of biological systems.
What is a temporal reaction network
Gene or Biochemical networks.
What is the goal of systems biology
To develop a quantitative understanding of the biological function of genetic and biochemical networks
What is a network
How things relate to other things (in a biological context; how gene X relates to gene Y etc)
What is Michaelis Menten kinetics (AKA lass of mass action)
E + S ES -> E + P
Where E = enzyme; S = substrate; P = product.
How can the Michaelis Menten equation be used to work out the concentration change of an enzyme/substrate/product
To work out the concentration change:
Minus anything that creates it; add up anything that uses it up.
What is the Michaelis Menten equation
v = Vmax[S] / Km + [S]
where Km = Kr+Kcat / Kf ; and Vmaz = Kcat[C]o
What are the two types of Hill function
Normal ‘Hill function’ - positive curve
Repressor Hill function - negative curve
Describe the process of negative auto regulation
The product of transcription acts as a repressor of the transcription reaction.
Why is negative regulation important in cells
Prevents build up
Increases reaction rate
What is the difference between negative and positive auto-regulation
Neg is much faster
Pos is much slower
(than simple outside regulation)
What are the two classes of loops that exist when 3 interactions are involved
Feed-forward loop
Feed-back loop (cycle)
How many types of feed-forward loop exist (3 interactions)
8
4 - coherent
4 - incoherent
What is the difference between coherent and incoherent feed-forward loops
Coherent - no change in sign. No contradicting stimulation/inhibitions
Incoherent - change of sign. Contradictions present.
What are the two most common types of feed-forward loop
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.
What does the graph look like for a coherent type 1 feed-forward loop
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.
What is the benefit of a coherent type 1 feed-forward loop
Filters out small perturbations.
X can randomly briefly activate, however Y does not reach the required concentration to activate Z (unless genuine stimulation).
Give examples of a coherent type 1 feed-forward loop
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)
What does the graph look like for an incoherent type 1 feed-forward loop
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.
What is the benefit of an incoherent type 1 feed-forward loop
There is only a brief increase in levels of Z gene.
Increased rate of response.
Give an example of an incoherent type 1 feed-forward loop
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).
How can network responses (reactions) be sped up
Increased degradation rate
Use of Negative feedback
Use of Incoherent feed forward loop.
What are the two types of movement a cell makes
Run (straight line)
Tumble (no movement, randomly changes direction)
What is the difference between a random walk and a biased random walk
Biased is semi-directional - random movements, but will tend toward a higher concentration.
Random has no tendency.
How are the two types of cell movement achieved
Movement of the flagellar. Can move clockwise or anticlockwise. This determines whether the cell ‘runs’ or ‘tumbles’.
What is the Gierer-Meinhardt model for pattern formation
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.
What are the two types of Gierer-Meinhardt diffusion
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.
Give an example of the Gierer-Meinhardt model for pattern formation
Chemotaxis signalling pathways in Dictyostelium.
Activator - PI3 kinase
Inhibitor - PTEN
They counteract each others cellular effects; and regulate.
How can the chemotactic response be changed/amplified
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.
What dose LEGI stand for
Local activation-global inhibition
Define chemotaxis
The movement of an organism in response to a chemical stimulus
What are the two competing models for chemotaxis
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.
How is a compass/LEGI mechanism involved in cell movement
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.
