Week 07 – Genetic Circuits Part II

Part 1: Intracellular Artificial Neural Networks

Q.1. Traditional genetic circuits mostly behave like Boolean logic, meaning everything is either ON or OFF. That works for simple designs like AND or OR gates, but it doesn’t really match what actually happens inside cells.

In real biology, nothing is strictly binary. Gene expression can be low, medium, or high, and signals are noisy and constantly changing. So forcing everything into ON/OFF makes the system too limited.

IANNs are different because they allow the cell to deal with inputs more flexibly. Instead of just switching ON or OFF, the system can combine multiple inputs with different strengths. One input might have a stronger effect, another might weaken the output, and the final result depends on the overall combination.

Also, these systems can be layered, meaning one step produces something that regulates the next step. This makes the behavior more complex and closer to how real biological systems actually work. So overall, IANNs are more useful because they allow continuous, tunable, and more realistic decision-making inside cells, instead of forcing everything into simple logic gates.

Q.2. If I think about where an IANN is actually useful, it’s when one signal is not enough and you need some kind of decision inside the cell, not just detection.

A simple example would be something like stress sensing. Cortisol alone is not reliable, and the same goes for any single marker. So instead of building one sensor per molecule, the idea is to combine multiple inputs and only produce an output when the combination actually makes sense biologically. From the kind of systems shown in work like CRISPR gene regulation (Nissim et al., 2017) and RNA-based control systems (Green et al.), we already know cells can integrate multiple inputs at the gene expression level.

Part 2: Fungal Materials

Q.1. Fungal materials, particularly mycelium-based composites, are already being used in several applications. Studies such as those on mycelium materials show that these materials can be used for packaging, leather alternatives, insulation panels, and lightweight structural components. In these systems, fungal mycelium grows through agricultural waste and binds it together into a solid material, meaning the material is grown rather than manufactured.

The main advantages of fungal materials compared to traditional materials are related to sustainability. They are biodegradable, require low energy to produce, and can use waste as a substrate. They also have useful properties such as low density and good insulation. Because of this, they are considered strong alternatives to petroleum-based materials like plastics and foams.

However, they also have limitations. Their mechanical strength is generally lower than traditional construction materials, making them unsuitable for load-bearing applications. They are also sensitive to moisture, which can affect their stability and durability. In addition, their properties can vary depending on growth conditions, which makes standardization difficult. Production is also slower compared to conventional manufacturing processes.

Q.2. Genetically engineering fungi offers an opportunity to move beyond passive materials and create systems with controlled or responsive behavior. Instead of only improving growth, fungi could be engineered to have enhanced material properties, such as increased strength or reduced water absorption. More importantly, they could be engineered to respond to environmental signals, for example by changing color, producing a detectable signal, or altering their structure under certain conditions.

This opens the possibility of combining material formation with sensing and decision-making, especially if integrated with systems similar to IANNs. In this case, fungal materials would not only exist as structures but could also act as responsive systems that process inputs and produce outputs.

Compared to bacteria, fungi offer several advantages for this type of application. While bacteria are easier to engineer and grow faster, fungi naturally form complex three-dimensional structures and are better suited for material-based applications. They can grow on low-cost substrates and are capable of producing and secreting complex molecules. This makes them more suitable for applications where physical structure and environmental interaction are important.

However, bacteria remain preferable for simpler and faster genetic systems due to their ease of manipulation and well-established tools. Therefore, the choice between fungi and bacteria depends on the application: bacteria are more suitable for controlled molecular systems, while fungi are more suitable for structural and material-based systems.

Refrences:

Nissim, L., Perli, S. D., Fridkin, A., Perez-Pinera, P., & Lu, T. K. (2014). Multiplexed and programmable regulation of gene networks with an integrated RNA and CRISPR/Cas toolkit in human cells. Molecular Cell, 54(4), 698–710.

Qi, L. S., Larson, M. H., Gilbert, L. A., Doudna, J. A., Weissman, J. S., Arkin, A. P., & Lim, W. A. (2013). Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Nature Biotechnology, 31(3), 233–239.

Green, A. A., Silver, P. A., Collins, J. J., & Yin, P. (2014). Toehold switches: De novo-designed regulators of gene expression. Cell, 159(4), 925–939.

Jones, M., Bhat, T., Huynh, T., Kandare, E., Yuen, R., Wang, C. H., & John, S. (2020). Engineered mycelium composite construction materials: A review. Fungal Biology Reviews, 34(4), 162–173.

Appels, F. V. W., Camere, S., Montalti, M., Karana, E., Jansen, K. M. B., Dijksterhuis, J., Krijgsheld, P., & Wösten, H. A. B. (2019). Fabrication factors influencing mechanical, moisture- and water-related properties of mycelium-based composites. Scientific Reports, 9, 1–11.