Week 7 — Genetic Circuits Part II: Neuromorphic Circuits

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

IANNs provide graded and analog computation rather than a strict ON/OFF logic. Enabling cells to integrate multiple inputs with tunable weights and produce continuous outputs that reflect the signal strength, not just presence/absence. IANNs can implement thresholding, nonlinear decision boundaries, and noise tolerance, making them more robust in heterogeneous biological environments. They also allow combinatorial regulation, which is difficult to achieve with simple Boolean gates without increasing the circuit complexity.

  1. 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: Smart infection biosensor (multi-signal decision)

Goal: Detect a pathogenic state only when a specific combination of biomarkers is present at sufficient levels.

Inputs (continuous, not binary) X1: Inflammatory cytokine level (Proxy via promoter responsive to NF-κB) X2: Bacterial quorum signal (AHL-responsive promoter) X3: Hypoxia signal (HIF-responsive promoter)

Network behavior (IANN) Each input drives expression of regulatory RNAs/proteins that act as weights (RNA regulators). The network computes a weighted sum:

  • High X1 and X2, moderate X3 → output ON (pathogenic infection)
  • High X1 alone → output low (inflammation but not infection) A thresholding layer converts the summed signal into a measurable output.

Output Fluorescent protein (GFP) or therapeutic gene (antimicrobial peptide). Output intensity reflects strength of classification

Why IANN is useful here

  • Avoids false positives from single signals
  • Integrates multiple noisy biomarkers
  • Produces graded output for better diagnostics

Limitations of IANNs

  • Biological noise: stochastic gene expression affects weights and outputs
  • Tuning difficulty: precise control of weights (promoter/RBS strength) is nontrivial
  • Crosstalk: regulatory parts may interfere with each other
  • Metabolic burden: multi-layer circuits can slow growth
  • Latency: transcription/translation delays limit response time
  • Scalability: adding layers increases complexity and failure modes
  1. Draw a diagram for an intracellular multilayer perceptron where layer 1 outputs an endoribonuclease that regulates a fluorescent protein output in layer 2.

X1 ─── Tx ─── Tl ───► (Csy4 protein) ─────┐ │ X2 ─── Tx ────────────────────────────────┼──► (mRNA GFP with Csy4 sites) ─── Tl ───► GFP (fluorescence) │ [Layer 2 regulation: cleavage/inhibition]

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

Mycelium-based composites Basidiomycetes dominate for composites and “pure mycelium” sheets. A concrete example are insulation boards made with Pleurotus ostreatus and Ganoderma lucidum grown on wheat straw to generate mycelium-based boards. A widely cited commercial packaging example is Mushroom® Packaging (MycoComposite™), marketed as a regenerative alternative to plastic foams; the company describes it as “mycelium + hemp hurd,” home-compostable in 45 days under appropriate conditions. Compared with petroleum foams (e.g., EPS), MBCs offer biodegradable end-of-life and the possibility of using waste feedstocks, but typically require moisture-protective coatings or application environments that limit water exposure. Risk-focused analysis also emphasizes that durability under humid weathering is a key performance gap; coatings help but may not fully seal porous composites.

Fungal leather and leather-like mycelium sheets A premium commercial entrant is MycoWorks, which markets “Reishi™” made via its patented “Fine Mycelium™” process (engineered interlocking cellular structures) and states it uses chrome-free tanning/dyeing technologies in finishing. In contrast, Bolt Threads states it has discontinued development and manufacturing of its mycelium leather product Mylo™, illustrating the real-world challenge of financing and scaling novel biomaterials through commodity-like production economics. Mycelium leather aims to reduce reliance on livestock and fossil based polymers while enabling biodegradability; however, most formulations still require finishing chemistry (tanning/crosslinking, coatings) to match abrasion/water resistance of incumbent leathers, and consistent quality at scale remains an open challenge in the literature.

Fungal-derived chitin and chitosan KitoZyme positions itself as a major manufacturer of fungal-origin chitosan and chitin-glucan, targeting cosmetics, agriculture, healthcare, and winemaking. Regulatory signals also exist: the U.S. Food and Drug Administration GRAS notices database lists “Chitosan from Aspergillus niger” and “Chitin-glucan from Aspergillus niger” among reviewed notices, indicating pathway precedent for food-contact/ingredient contexts depending on use case and dossier. Fungal chitosan often compares favorably on allergen/mineral contamination risk and supply-chain stability (fermentation vs seafood seasonality), but can still face higher production costs for bulk commodity uses (e.g., large-scale water treatment) and must meet rigorous purity/toxin specifications for biomedical and food uses.

Fungal pigments Carotenoids deliver color and antioxidant functionality and are used in food/feed/cosmetics; the review emphasizes broad carotenoid diversity in fungi and notes fungi can be strong hosts for carotenoid production relative to some alternative platforms.

  1. 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?

  • I would engineer fungi to produce enhanced mycelium-based biomaterials with increased mechanical strength and environmental responsiveness, by modifying cell wall composition and introducing synthetic protein scaffolds. This leverages fungi’s natural ability to form structured materials while enabling sustainable alternatives to plastics and leather.

  • A core reason is that fungi combine eukaryotic cell biology with an industrially proven capacity for secretion and materials formation. Filamentous fungi are eukaryotes with ER/Golgi pathways and PTMs that bacteria generally lack; reviews emphasize strategies such as engineering glycosylation sites, unfolded protein response (UPR) management, and secretion pathway optimization to improve heterologous protein output.

  • A cell-wall biotechnology review states that filamentous fungi can outperform bacteria and yeasts in secretion efficiency, reaching reported secreted protein levels up to ~100 g/L in some contexts. Unlike bacteria, fungi naturally build macroscopic fibrous networks (mycelia) that act as binders and scaffolds. MBCs explicitly exploit this to bind particles into solids; biomineralized ELM work likewise uses mycelium as a scaffold for functional composites. Filamentous fungi are specialized decomposers; reviews emphasize their ability to depolymerize complex substrates externally by secreting enzymes, allowing direct use of lignocellulosic wastes and diverse sugars, feedstocks that many bacteria cannot access without extensive pre-processing.

  • Fungal systems are generally slower-growing and introduce additional process complexity due to morphology (pellets vs dispersed hyphae) affecting viscosity, mixing, and oxygen transfer. Tool maturity is improving but still uneven: a domestication-focused review highlights challenges such as locus biases, transformation efficiencies, and limited cross-species part libraries, issues that are often less severe in mature bacterial chassis ecosystems.