Week 7 — 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?

IANNs provide a significant advantage over Boolean genetic circuits by enabling analog computation, which allows cells to process a continuous range of signal concentrations rather than simple on/off states. This capability leads to more efficient signal integration, as a single layer can replace complex cascades of logic gates, while offering greater tunability by adjusting molecular weights like promoter strengths without re-engineering the entire system.

  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.

A practical application for an IANN is a smart metabolic regulator for conditions such as diabetes, where inputs like glucose and GLP-1 levels are weighted to produce a graded output of insulin. This mimics natural pancreatic behavior more closely than a binary response, although it faces limitations such as molecular noise and metabolic burden, which can lead to leaky expression or reduced cellular fitness during high computational demands.

  1. Below is a diagram depicting an intracellular single-layer perceptron where the X1 input is DNA encoding for the Csy4 endoribonuclease and the X2 input is DNA encoding for a fluorescent protein output whose mRNA is regulated by Csy4. Tx: transcription; Tl: translation.

In the provided diagram, the Csy4 endoribonuclease acts as an inhibitory input that regulates the output of the fluorescent protein by cleaving its mRNA. The system functions as a molecular perceptron where the final fluorescence depends on the balance between the transcription of the reporter gene and the repressive activity of Csy4, effectively performing a subtraction-based calculation within the cell.

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?

Existing fungal materials, often called mycelium-based composites, include sustainable alternatives for packaging, construction bricks, and vegan leather. In packaging, mycelium is grown on agricultural waste to replace polystyrene, while in construction, it is used to create lightweight, fire-resistant insulation panels or acoustic tiles. Compared to traditional materials like plastic or concrete, fungal materials are biodegradable, carbon-negative, and require significantly less energy to produce; however, they currently face disadvantages such as lower structural strength, sensitivity to high humidity, and slower production times compared to synthetic manufacturing.

  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?

Genetically engineering fungi could enable the production of specialized enzymes for plastic degradation or the synthesis of complex pharmaceutical compounds like precursor molecules for antibiotics and anticancer drugs. Fungi are particularly advantageous for synthetic biology because, as eukaryotes, they possess advanced protein folding and post-translational modification machinery that bacteria lack, allowing them to produce functional human-like proteins. Additionally, their robust secretome allows them to export large quantities of products directly into the growth medium, simplifying the purification process compared to the intensive recovery methods often required for bacterial intracellular production.