Austin Clyde

MENG 346
Assignment 1
Coherent Type 2 FFL is an Ineffective Signal Transducer
The appearance of C2-FFL loops in biological networks is not statistically significant,
especially compared to C1-FFL or L1-FFL loops. C1-FFL, for example, is a sign sensitive delay
element which can reduce signal noise. These loops have functions that generally cannot
be implanted with similar circuits. C2-FFL with both AND or OR activation functions
reduce to simpler circuits which only one factor versus two, which is preferably
biologically as using multiple signaling mechanisms requires energy.
C2-FFL with AND:
Assuming the Z activation requires not X* and Y*, there are a few cases to Figure 1 Coherent
consider. First, assume a persistent Sx signal. X* becomes activate and inhibits production Type 2 Feed
Forward Loop. See
of Y* and also inhibits production of Z. If Sy occurs, production of Z* is still not note 1.
activated since Z is inhibited by X*. Consider the truth table for the circuit1
SX SY Change in Z
0 0 0
0 1 1
1 0 0
1 1 0
This truth table would lead the question why is X involved in the circuit or why has Y not
evolved to modulate Z correctly? One possible use would be if Sy is saturated then the signal of
Sx could turn off production, or even if there is signal Sy, do not produce Z in the presence of Sx
(yet both cases do not require X to interact with Y). Using negative autoregulation for Y would
reduce the need for another signaling mechanism and function somewhat similarly given the
hypothesis. Lastly, response time in this system is not interesting as there is no cascade in the
sense that we always have to consider SX and SY separately and not the dynamics between
cascading from X* to Y* to Z* as in C1-FFL.
C2-FFL with OR:
Given the very short-sighted look at this motif, the OR C2-FFL ends up functioning the
same as a simpler mechanism with just X* as a single inhibitor. Given the table below, the
circuit is the same as X* as a single input to Z, as the value of Y does not alter production.
SX SY Change in Z
0 0 1
0 1 1
1 0 0
1 1 0
If we consider the behavior beyond the Boolean circuit behavior using a step function for the
production function of Z and assume SY is persistent, the C2-FFL motif could function as a
simple modulation of Z production by SX, turning X* on when Y has accumulated. Again, this
hypothesis can be achieved with negative autoregulation on Y and even a second input inhibition
by X*, but X and Y do not need to interact in this case. Reponse times are similar to the AND
case as activation of Z is soley dependent on the lack of SX.

1
Idea for using truth tables came from Harvard lecture slides for the course MCB 195: A systems approach to
biology (no professor attributed). http://sites.fas.harvard.edu/~mcb195/sections/Section_5/netMotifs4section.ppt