Week 7 HW: genetic-circuits-part-ii

Task Part 1: Intracellular Artificial Neural Networks (IANN)

1. Advantages of IANNs vs. Boolean Logic

Continuous/gradual response (not just ON/OFF)
Integrate multiple weighted signals (weighted sum type)
Allow thresholds, nonlinearity, and fine-tuning
Greater robustness to biological noise
Scalability for complex functions (not just AND/OR)

2. Useful Application (example: intelligent intestinal biosensor)

Input:
X1 = microbial metabolites (SCFAs)
X2 = inflammatory signal (NF-κB)
X3 = drug present
Behavior:
The IANN integrates signals → calculates an “activation”
If it exceeds the threshold → activates the expression of a therapeutic (or fluorescent) protein

Output:
Proportional protein production (non-binary)

Limitations:

Cellular noise and variability
Difficulty in adjusting “biological weights”
Slow kinetics (Tx/Tl)
Cellular metabolic load
Interference with endogenous networks

3. Intracelular Perceptron

This figure illustrates a synthetic biological perceptron designed to sense gut metabolic signals. The circuit integrates two key inputs, short-chain fatty acids (butyrate) and bile acids, which modulate the expression of RNA-processing enzymes. These enzymes control the stability of the reporter mRNA (mNeoGreen), determining fluorescence output. The system discriminates between dysbiotic and healthy states based on the combined input signals.

Circuit interpretation:

The system works like a biological perceptron that integrates two environmental signals:

X1 (butyrate/SCFAs) → inhibitory signal
X2 (bile salts) → activating signal

Under normal conditions (healthy state):

High X1 represses CasE expression
X2 at basal levels does not activate Csy4
As there is no processing of the output RNA (NG, mNeoGreen), it is translated correctly = there is controlled basal fluorescence or absence of cleavage = “off” circuit in terms of dysbiosis response

In conditions of dysbiosis:

Decrease in X1 = CasE expression is disinhibited
Increase in X2 = activates Csy4 expression
Both effectors process/cleave NG RNA = translation is blocked = no fluorescence