Week 7 Genetic Circuits Part II: Neuromorphic Circuits

Genetic Circuits Part II: Neuromorphic Circuits

Part 1: Intracellular Artificial Neural Networks (IANNs)

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

Traditional genetic circuits tend to have a more restricted set of states they can use to respond to stimuli. IANNs support analog signal processing, which allows them to continuously adapt and respond to varying conditions instead of set of those that only register as ‘1’s or ‘0’s. This property can make them better suited to cope with the environmental bioprocesses that can exhibit different metabolic properties depending on their location in space and time ¹. IANNs are also better able to respond to noise in signals than traditional genetic circuits.

I think it would be interesting to create an IANN to support people who have hemochromatosis, a disorder that causes the body to absorb too much iron. An IANN would rely on measuring a analogue signnal of free iron concentration. The processing part of the circuit would involve summing the input signal of Fe concentration to detect when it passed a certain level. When the threshold was reached, the circuit could encourage further ferritin synthesis, perhaps such that the amount produced matched the amount of free iron.

I don’t know if it’s a weakness but I’d wonder how long engineered cells would last in the body. I’d also wonder whether parts of the circuit would have a risk of changing - for example somehow as the circuit ages, the threshold of when it starts producing ferritin gets lower and lower (producing too much response) or higher and higher (triggering too little response)

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.

Draw a diagram for an intracellular multilayer perceptron where layer 1 outputs an endoribonuclease that regulates a fluorescent protein output in layer 2. I’m having trouble understanding this and spent half an hour on it before giving up to get more help on it. I understand that the perceptron f1 would take as input the x1 - the DNA encoding for the Csy4 endoribonuclease and something else that could turn that ‘on’ or ‘off’. That output would then feed into the diagram that’s shown, and the presence of endoribonuclease would turn ‘off’ the production of fluorescent proteins. Beyond that I’m not sure.

Part II

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 (the vegetative part of fungi) can be used to produce insulation, packaging, or construction materials. Mycelium is also used to make a leather-like substance to make fashion items ². Research has also found that mycelium can be made to create a self-repairing fabric.³

Mycelium material can provide a biodegradable alternative to synthetic materials.⁴ There are claims that it can be more environmentally friendly, but I think the costs of growing it and reusing it at large scale need to happen before I can evaluate that claim.

The disadvantages of mycelium materials is that growing it for large-scale activities may be challenging. Its properties may not be as consistent as those of synthetic materials and its biodegradability means it would likely not be as durable.⁵

Also note fungal materials are also used to detect food pathogens, provide antibiotics, and alternative food materials to meat.

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 can be genetically engineered to support bioremediation applications (e.g. sequestering heavy metals).⁶ For example, Jo reports that:

"Compared with bacteria, which are widely deployed for    bioremediation and typically require a continuous water phase to grow, filamentous fungi can extend their mycelia across the air-liquid interface into air-filled pores in the soil. Fungal mycelia can thus reach areas inaccessible to bacterial biofilms and form bridges transporting nutrients and chemicals across discontinuous microhabitats. In these environments, fungal cells absorb molecules from enzymatic degradation together with other chemicals, such as heavy metals and metalloids, and convert them into less toxic forms intracellularly."