Week 7 HW: Genetic Circuits Part II: 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?
While traditional genetic circuits operate on binary logic (0 or 1), Intracellular Artificial Neural Networks (IANNs) utilize an analog approach that more accurately reflects biological reality. Their primary advantages include:
- Realistic Analog Processing: Biology rarely exists in a strictly “on/off” state. IANNs can process continuous gradients of expression, allowing the cell to make decisions based on subtle shifts in concentration rather than waiting for a digital threshold.
- Weighted Decision Boundaries: In a Boolean circuit, adding a new “condition” usually requires engineering entirely new genetic parts from scratch. In an IANN, you can adjust the “weight” of an input (e.g., by changing the binding affinity of a protein or the strength of a promoter), allowing for complex tuning without redesigning the whole system.
- Advanced Logic (The “Dual Region” Zone): IANNs enable “non-monotonic” logic. For example, a cell can be programmed to activate only when an input is strictly below or strictly above a certain range, remaining inactive in the middle. This “band-pass” behavior is incredibly difficult to achieve with standard AND/OR gates.
- Pattern Recognition: IANNs are superior at integrating multiple “weak” signals. Instead of requiring one signal to be 100% “on,” the network can sum several 20% signals to trigger a response, making them ideal for sensing complex environmental or disease signatures.
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.
Goal: A synthetic IANN designed for a bioremediation host (like P. putida) that triggers a cleanup response only when a specific ratio of heavy metals and organic pollutants is detected.
- Input Behavior: The network senses three distinct analog inputs: Lead (Pb2+), Arsenic (As3+), and Toluene.
- Output Behavior: The IANN calculates a weighted sum. If the “toxic signature” matches a specific profile (e.g., high Lead + moderate Toluene), it triggers the expression of degradative enzymes. If the inputs fall outside these specific “decision boundaries” (e.g., Lead is too low to be a threat, or so high it would kill the host), the output remains at 0 to conserve energy.
Limitations to Implementation
- Metabolic Sequestration (The ERN Cost): Using Endoribonucleases (ERNs) to control the network is powerful but “expensive.” Because ERNs often bind to and hold RNA rather than instantly destroying it, they sequester cellular resources. A large IANN could potentially “clog” the cell’s translational machinery, leading to reduced fitness or growth arrest.
- Orthogonality Scalability: As the circuit grows more complex to handle more inputs, you need an increasing number of unique ERNs. If these ERNs overlap in their target sequences, “cross-talk” occurs, where one branch of the neural network accidentally silences the wrong target, leading to a total failure of the logic.
- Stochastic Noise: In an analog system, small random fluctuations in molecular counts (noise) can shift the decision boundary, potentially causing a “false fire” in a sensitive environment.
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?
Fungal materials, often referred to as mycomaterials, primarily utilize mycelium which is a vegetative, root-like network of a fungus.
- Mycelium Composites (Bio-foams & Bricks)
How they’re made: Fungi are grown on agricultural waste (hemp, sawdust, rice hulls). The mycelium acts as a natural “glue,” binding the substrate into a solid form.
Applications:
- Packaging: Companies like Ecovative produce biodegradable alternatives to Styrofoam.
- Construction: Mycelium bricks and insulation panels. Notable projects like “Hy-Fi” (a 40-foot tower in NYC) have demonstrated their structural potential.
- Acoustics: Sound-absorbing wall tiles for studios and offices.
- Mycelium Leather (Myco-leather)
How it’s made: Pure mycelium is grown in mats, then tanned and processed like animal hide.
Applications: High-fashion items (e.g., Hermès and Adidas have explored mycelium leather), upholstery, and automotive interiors.
- Fungal Textiles and Films
- Applications: Biodegradable films for wound healing or flexible electronic substrates.
Advantages and Disadvantages vs. Traditional Counterparts
| Feature | Fungal Materials | Traditional (Plastics/Leather/Concrete) |
|---|---|---|
| Environmental Impact | Carbon-negative/neutral. Uses waste and is biodegradable. | High carbon footprint; fossil-fuel based or methane-heavy (livestock). |
| Manufacturing | Grown in days; low energy/water requirements | Energy-intensive chemical synthesis or years of livestock raising. |
| Performance | Excellent thermal/acoustic insulation; natural fire resistance. | Variable; plastics are durable but toxic when burned. |
| Durability | Disadvantage: Sensitive to moisture and can biodegrade prematurely if not treated. | Extremely durable and weather-resistant. |
| Consistency | Disadvantage: Biological variability makes standardization difficult. | Highly predictable and standardized properties. |
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?
Fungi offer a unique chassis for synthetic biology. I would love to use it to produce scorpion venom peptides but there are other appliations too.
Potential Engineering Goals
- Material Customization: Engineering fungi to produce more chitin for stiffer bricks or more hydrophobins for water-resistant leather.
- Self-Healing Materials: Designing fungi that remain “latent” in a material and reactivate to repair cracks when exposed to moisture or specific nutrients.
- Biosensors: Programming mycelium to change color or produce a signal in the presence of environmental toxins or pathogens.
- Biopharmaceuticals: Engineering filamentous fungi (like Aspergillus niger) to secrete complex human proteins or secondary metabolites for cancer therapy.
Advantages of Fungi vs. Bacteria in Synthetic Biology
- Post-Translational Modifications (PTMs): As eukaryotes, fungi can perform complex PTMs (like glycosylation) that bacteria cannot. This is crucial for producing functional human-like proteins.
- Secretion Powerhouses: Filamentous fungi are natural champions at secreting large amounts of enzymes and proteins directly into their environment, simplifying the “harvesting” process compared to lysing bacterial cells.
- Complex Metabolism: Fungi possess vast biosynthetic gene clusters (BGCs) for secondary metabolites, making them superior for discovering and producing new antibiotics or anticancer drugs.
- Structural Growth: Unlike bacteria (which grow as a “soup” or biofilm), fungi grow as a 3D physical network. This allows for the engineering of living materials with specific mechanical architectures.