Week 7 HW: Genetic Circuits partII: Neuromorphic circuits

Assignment Part 1: Intracellular Artificial Neural Networks (IANNs)

1. What advantages do IANNs have over traditional genetic circuits, whose input/output behaviors are Boolean functions?

Traditional genetic circuits mostly behave like Boolean logic gates (ON/OFF). Intracellular Artificial Neural Networks (IANNs) are more flexible.

Advantages:

a. Analog (continuous) behavior

-> Traditional circuits: only 0 or 1 (OFF/ON)

-> IANNs: can process graded inputs (like protein concentration levels). More similar to real biological systems

b. Ability to learn complex patterns

-> Boolean circuits struggle with complex relationships

-> IANNs can approximate nonlinear functions.Useful for detecting subtle biological signals

c. Multivariate decision-making

-> Traditional: limited number of inputs

-> IANNs: integrate multiple inputs simultaneously. Example: detecting disease based on multiple biomarkers

d. Noise tolerance

-> Biological systems are noisy

-> Neural-like circuits can be designed to be robust to fluctuations

e. Scalability

-> Hard to scale Boolean circuits without complexity exploding

->IANNs naturally scale into layers (like perceptrons)

2.Describe a useful application for an IANN; include a detailed description of input/output behavior, as well as any limitations an IANN might face to achieve your goal.

Application of an IANN: Microplastic Detection and Filtering System

Description:

An intracellular artificial neural network (IANN) can be engineered in microbial cells to detect and respond to the presence of microplastics in aquatic environments. Since microplastics are not directly sensed biologically, the system relies on indirect chemical and physical signals associated with plastic contamination.

Input Behavior:

The system takes multiple inputs encoded as DNA sensors:

X1: Detects plastic-associated chemicals (e.g., bisphenol-like compounds released from plastics)

X2: Detects hydrophobic particle interactions (via surface-binding proteins)

X3: Detects oxidative stress caused by microplastic exposure

X4: Detects co-contaminants that commonly adsorb onto microplastics

Each input produces a graded transcriptional response, resulting in varying levels of regulatory proteins inside the cell.

These inputs are weighted and integrated by the IANN through regulatory elements such as transcription factors or endoribonucleases, allowing the system to compute the overall likelihood of microplastic contamination.

Output Behavior

The output depends on the combined input signal:

-> When the integrated signal is below threshold → minimal or no response

-> When the integrated signal is above threshold → activation of output genes

Possible outputs: a. Fluorescent protein expression

b. Indicates presence of microplastics (detection mode)

c. Expression of plastic-binding proteins or enzymes (e.g., PET-degrading enzymes)

d. Enables capture or partial degradation of microplastics (filtering mode)

This allows the system to act as a smart biosensor and response unit, activating only when contamination is significant.

Limitations: -> Indirect detection: Microplastics are not directly sensed; accuracy depends on proxy signals

-> Biological noise: Variability in gene expression may affect reliability

-> Slow response time: Transcription and translation processes delay output

-> Environmental safety concerns: Release of engineered microbes into natural ecosystems poses risks

-> Limited degradation efficiency: Biological breakdown of plastics is slow and incomplete

Ans:

Layer 1 produces an endoribonuclease (Csy4) that negatively regulates fluorescent protein expression in Layer 2 by cleaving mRNA.

Assignment Part 2: Fungal Materials

1. What are some examples of existing fungal materials and what are they used for? What are their advantages and disadvantages over traditional counterparts?

Ans: i) Examples of fungal materials & their uses

a. Mycelium-based materials

Example: Ecovative Design products

Uses: -> Packaging (alternative to Styrofoam)

-> Building materials (insulation, bricks)

-> Furniture

b. Fungal textiles

Uses:

-> Sustainable fabrics

-> Biodegradable fashion materials

ii) Advantages over traditional counterpart

a. Biodegradable: Break down naturally (unlike plastics)

b.Sustainable: Grown from agricultural waste

c.Low energy production: No high-temperature industrial processes

d.Carbon sequestration: Can store CO₂ during growth

e.Customizable growth: Shape materials during growth

iii) Disadvantages

a. Lower durability: Not as strong as metals or high-grade plastics

b. Moisture sensitivity: Can degrade in humid environments

c.Scaling challenges: Hard to mass-produce consistently

d.Slower production: Growth takes days vs instant manufacturing

e.Limited lifespan: Not ideal for long-term structural use

2. What might you want to genetically engineer fungi to do and why? What are the advantages of doing synthetic biology in fungi as opposed to bacteria?

Ans: I want to genetically engineer the fungi for the following reasons:

a. Fungi can be engineered to produce materials with improved performance. Because This allows development of lightweight, biodegradable composites with mechanical properties closer to plastics or wood-based materials.

b. Fungi naturally produce extracellular enzymes capable of breaking down complex substrates.Because this expands fungal capability for bioremediation, enabling degradation of persistent materials such as plastics, dyes, and hydrocarbons under mild environmental conditions.

c. Fungal mycelium can be engineered to respond dynamically to environmental stimuli. Because This enables adaptive materials that can self-repair, respond to damage, or change properties in real time.

Advantages of using fungi for synthetic biology vs bacteria

-> Eukaryotic system: Capable of complex protein folding and post-translational modifications, unlike many bacteria such as Escherichia coli

-> Secretion capacity: Efficient export of enzymes and metabolites simplifies downstream processing

-> Mycelial structure: Naturally forms 3D networks, enabling direct fabrication of structured materials

-> Substrate flexibility: Can utilize low-cost feedstocks (e.g., lignocellulosic waste)