Week 1 HW: Principles and Practices

1. First, describe a biological engineering application or tool you want to develop and why. This could be inspired by an idea for your HTGAA class project and/or something for which you are already doing in your research, or something you are just curious about.

The tool I want to develop is a Physarum-on-a-Chip environmental sensor (slime molds) that utilizes Controlled Chemotactic Gradient Arrays.

Ideas aournd: bio-inteligence, including the Memory Hack of slimemode;how does it memrozie the rounte. Even without a nervous system, they leave a trail of extracellular slime; enjoy projects training it and how deos the inetrcellualar pathways contribute to theirnetwork.

2. Next, describe one or more governance/policy goals related to ensuring that this application or tool contributes to an “ethical” future, like ensuring non-malfeasance (preventing harm). Break big goals down into two or more specific sub-goals. Below is one example framework (developed in the context of synthetic genomics) you can choose to use or adapt, or you can develop your own. The example was developed to consider policy goals of ensuring safety and security, alongside other goals, like promoting constructive uses, but you could propose other goals for example, those relating to equity or autonomy.

Because this tool integrates living organisms into computational and sensing infrastructures, ethical development requires attention to safety, ecological responsibility, transparency, and equitable use. Lab Safety -Physarum polycephalum is generally classified as Biosafety Level 1 (BSL-1). Because it is non-pathogenic and doesn’t cause disease in healthy humans, it is considered safe for most biology classrooms and general research labs

-Environmental Concern Because slime molds are highly adaptive “escape artists,” a primary goal is to prevent the accidental introduction of laboratory-optimized or potentially modified strains into local ecosystems.

Lecture Questions

1. Nature’s machinery for copying DNA is called polymerase. What is the error rate of polymerase? How does this compare to the length of the human genome. How does biology deal with that discrepancy?

Error Rate is 1/10^{6 throughout 10 mS per base addition; throughput Error Rate Product Differential: ~10}8. The human genome is approximately 3.2 Gbp, and human genome is roughly 6*10^{9 base pairs. With an error rate of 10}-6, a single replication cycle would still introduce thousands of errors. The DNA polymerase enzyme proofreads to make instant corrections. The MutS Repair System identifies the errors too.

Note from class: Almost everything built in nature will have a sort of error, the error fixing mechanism is universal. -Single strand DNA is double strand’s workspace (Prof. Church)

2. How many different ways are there to code (DNA nucleotide code) for an average human protein? In practice what are some of the reasons that all of these different codes don’t work to code for the protein of interest? For an average human protein, the coding sequence is about 1036 base pairs long. As mentioned earlier, there is a significant chance of error in translation, a random codon choices may accidentally creates a stop codon. Moreover, in the mRNA secondary structure, some sequences fold into strong hairpins and loops that disrupts the correct formation of protein.

3. What’s the most commonly used method for oligo synthesis currently? The dominant method is chemical solid-phase synthesis using phosphoramidite cycle.

4. Why is it difficult to make oligos longer than 200nt via direct synthesis? Because chemical synthesis has an error rate around 1/100 error per base, such error rate accumulate with every nucleotide addition.

5. Why can’t you make a 2000bp gene via direct oligo synthesis? Because the error rate increases exponentially as the length increases, too much errors would be created. (correction rate = 0.99^2000)

6. [Using Google & Prof. Church’s slide #4]   What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”? Arginine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine. Vertebrate animals cannot produce lysine, thus are structururally dependent on external biological systems.

7. [Given slides #2 & 4 (AA:NA and NA:NA codes)]   What code would you suggest for AA:AA interactions? NA:NA (Not sure)

8. [(Advanced students)]   Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own: