Systems Biology Flashcards
Systems Biology
- The computational and mathematical analysis and modeling of complex biological systems.
- Quantitative understanding of biological systems
- Note: Systems Biology =! Network Biology
e.g. The Human Genome Project
Michaelis–Menten Kinetics
Model of enzyme kinetics.
v = d[P]/dt = Vmax[S]/(KM + [S])
v = reaction rate (The rate of formation of product (P)) [S] = Concentration of substrate Vmax = the maximum rate achieved by the system (happens at saturating substrate concentration). KM = the substrate concentration at which the reaction rate is half of Vmax.
d[P]/dt = the rate of change of [P] with respect to time
Types of regulation:
- Positive regulation (X is an activator that activates Y expression)
- Negative regulation (Xis a repressor that inhibits Y expression)
- Simple regulation (transcription factor X regulates the expression of gene Y)
- Negative auto regulation (The product of a gene represses its own production. Can speed up response of a strong promoter)
- Positive auto regulation (The product of a gene activates its own production. Slows down response, compared to simple regulation)
The “Hill” function
Reflects the binding of ligands to macromolecules.
Generalisation of Michaelis-Menten kinetics
results in the “Hill” function: (Or rather, michaelis menten formula is the hill function when n=1)
f(X)= (βX^n)/(K^n + X*^n)
V = (Vmax[S]^n)/(Km^n + [S]^n)
n= Hill coefficient: larger n gives steeper function
Feed Forward Loop (FFL)
Node A
/ \
/ \
\/ \/
Node C B
Node B -> C
Node C -> A
These are the 2 classes of 3 node networks:
- Feed forward loops
- Feedback loops
There are X possible coherent and incoherent Feed Forward Loops (FFLs): Other information about coherent and incoherent FFLS and examples of them:
X = 8 (4 coherent, 4 incoherent)
e.g. Coherent: X –¦ Y
Y –> Z
X –¦ Z
e.g. Incoherent: X –> Y
Y –¦ Z
X –> Z
X causes both inhibition of Z production (through Y), and directly activates Z production: Therefore incoherent.
- Coherent Feed Forward loop results in delay of “on” response.
- Coherent Feed Forward loop has no effect on “off” response.
- Coherent Feed Forward network can filter out small perturbations
Real Life Example: Ara and lacZ locus regulation in E coli
- Incoherent feed-forward loop results in pulse like dynamics.
- Depending on repression strength pulse response of incoherent feed-forward loop can be sharp.
- Incoherent feed forward loop speeds up response time -compared to simple regulation reaching the same steady state level.
Real Life Example: E coli galactose system, Activated by glucose starvation which results in cAMP production.
Three ways to speed up network response:
- Increasing the degradation rate
- Use of negative feedback
- Use of incoherent feed forward loop
4 Node Generalisation of FFLs:
X1 -> Y X -> Y1 X -> Y
X2 -> Y X -> Y2 X -> Z1
X1 -> Z Y1 -> Z X -> Z2
X2 -> Z Y2 -> Z Y -> Z1
Y -> Z X -> Z Y -> Z2
Can generalise for even higher numbers but obviously gets much more complex.
Random Walk
Describes a path that consists of a succession of random steps on some mathematical space.
e. g. Diffusion is random walk
e. g. Start at origin, flip coin, if heads go right if, tails go left, flip coin again N times.
Bacterial movement in the absence of chemical attractant is a random walk.
Biased Random Walk
A random walk that is biased in one direction, leading to a net drift on average of particles in one specific direction.
Bacterial movement in the presence of chemical attractant is a biased random walk.
Bacterial Movement: Run and Tumble
Absence of chemical attractant = random walk
Presence of chemical attractant = biased random walk
Chemo-attractants control bacterial flagella rotation:
Counter-Clockwise = Run
Clockwise = Tumble
Bacteria swim towards attractants and away from repellents by modulating tumbling frequency:
e. g. Chemotaxis system of E.coli
- Attractants switch CheY kinase off and suppress tumbling
- CheA phosphorylates CheY, which stimulates tumbling
How is amoeboid cell movement driven?
By actin polymerisation at the leading edge and a myosin II driven retraction at the rear:
- Extension (at front)
- Attachment (to new front surface)
- Contraction (at rear)
Dictyostelium development control and movement:
cAMP waves control all stages of Dictyostelium development.
Chemotactic movement to cAMP involves persistent extension of pseudopodia in the direction of the signal. This causes the cells to polarise and move directionally.
