I found myself very interested in the aspect of biosynthesis and engineering fabric-like material from microorganisms. The example shown in the first lecture of jackets made from bacterial cellulose piqued my curiosity in particular because it involves possibly making clothes from sustainable and biodegradable material instead of plastic. As a biology student, this application opened my eyes to a new and exciting path I could take in the future that is independent from medicinal applications. For now, I’m very curious about it. But hopefully, I will be able to make this my final project and get hands on experience in synthesizing such materials.
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? response:
The error rate of polymerase is one per million bases. Compared to the human genome which is in total 3.2 GBP, which means approximately 3000 errors per genome. The human body deals with this error through a few ways: 1) polymerase proofreading: this utilizes 3’-5’ exonuclease which splices out the wrong mismatched nucleotide from the 3’ end of the strand. This process happens while the DNA replication is active. 2) Mismatch repair: after DNA is finished replicating, proteins like MutS read the strand for incorrect pairings that have escaped the earlier proofreading. It, similarly, cuts out the incorrect nucleotide before resynthesizing that section. 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?
Subsections of Homework
Week 1 HW: Principles and Practices
I found myself very interested in the aspect of biosynthesis and engineering fabric-like material from microorganisms. The example shown in the first lecture of jackets made from bacterial cellulose piqued my curiosity in particular because it involves possibly making clothes from sustainable and biodegradable material instead of plastic. As a biology student, this application opened my eyes to a new and exciting path I could take in the future that is independent from medicinal applications. For now, I’m very curious about it. But hopefully, I will be able to make this my final project and get hands on experience in synthesizing such materials.
I view biosynthesizing fabric-like materials as an alternative to traditional methods that use plastics/nonbiodegradable materials. The traditional method contributes significantly to pollution and harms the environment. A governance goal would be to ensure that this technology is actually capable of reducing environmental harm when produced for industrial use. A sub goal can be verifying sustainability claims through experimental evidence and making sure the production process is safe for both the ecosystem and the workers. If this field is developed enough to find a way to scale this for industrial use, it could be a real game changer in the fashion industry while lessening environmental risks.
Ensuring biosynthesized materials are developed responsibly requires several governance actions that can be implemented by different major actors.
An important, and perhaps a primary, actor would be government and regulatory agencies. These organizations are capable of establishing biosafety rules that require laboratories to safely handle engineered microorganisms used in biofabrication. These rules aim to prevent accidents and protect public safety. These regulations involve creating a standardized process about containment and waste management that institutes must follow to receive licensing. The assumption here is that the companies would comply and strictly enforce the regulations. It could very well fail if the instructions are loosely enforced or, on the contrary, are too strict and restrictive, which might slow the creative process.
The second actor is biotech and fashion companies. These companies can contribute by implementing sustainable production practices as well as providing transparent information about their products. Advertising also plays a major role in how the customers would perceive this new invention. The purpose is for consumers to be aware of what they are purchasing, this can further raise awareness about the existence of a more ecofriendly way of consuming. This governance assumes multiple things; that the companies prioritize ethical responsibilities and that consumers will respond positively to the nature of biosynthesized products. A potential risk is that companies may lean towards misinformation, exaggerating or poorly marketing their products.
The third actor are universities and researchers. Researchers can study and evaluate the true environmental impact of biosynthesized materials; this would provide more concrete evidence that they’re safe for the environment as well as potentially developing a safer version of engineered microorganisms. The purpose is to provide reliable scientific evidence to act as a guide for industrial use. This assumes the willingness to fund the research and provided ethical supervision. A risk may be limited funding given the scale and material this kind of research requires.
(sorry, i made my original chart in Word. i couldnt transfer it here and i had trouble inserting an image so i used chatgpt to convert it to text.)
Based on the scoring, I would prioritize the actions that must be taken by regulatory agencies and biotech companies. They establish clear biosafety and clarify the environmental impact, all essential to ensuring that biosynthetic fabrics are produced in a safe and responsible manner. Biotech companies develop and scale products is necessary because without industry involvement this technology cannot become easily accessible to the masses. These actions balance creativity, engineering and safety, contributing to the field growth while minimizing environmental risks. a potential trade off is that strict regulations may slow the researching process and increase production costs. and because this is still a developing field, there is no garanty about its long term impact on the enviroment. an ethical concern i found in the topics covered during the lecture would be automating protein monitoring. though it is much faster than humans, it is susceptible to error and biases. governance actions to address this concern maintaining regular human reveiewing to ensure no errors or contamination goes unnoticed.
Week 2 HW: Pre lecture
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?
response:
The error rate of polymerase is one per million bases. Compared to the human genome which is in total 3.2 GBP, which means approximately 3000 errors per genome. The human body deals with this error through a few ways: 1) polymerase proofreading: this utilizes 3’-5’ exonuclease which splices out the wrong mismatched nucleotide from the 3’ end of the strand. This process happens while the DNA replication is active. 2) Mismatch repair: after DNA is finished replicating, proteins like MutS read the strand for incorrect pairings that have escaped the earlier proofreading. It, similarly, cuts out the incorrect nucleotide before resynthesizing that section.
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?
The average human gene for a protein is 1036 Bp according to Professor Jacobson. And there are four nucleotides that make up the human genome (A,T,C,G). So, if we want to know all the possible ways we can code for a single gene, we must raise 4 to the power of 1036, which ultimately gives us 10^623 possibilities. There are multiple reasons why not all codes work efficiently to code for certain proteins. Codon bias, for example, entails that rare codon is slower to translate due to a different tRNA availability. Though the tRNA is always there, it might take longer to translate a rare codon which would stagger the process. mRNA can be slower to recognize the start site in the presence of strong secondary structures.
What’s the most commonly used method for oligo synthesis currently?
As described in professor Leproust’s slides, solid phase phosphoramidite oligonucleotide synthesis.
Why is it difficult to make oligos longer than 200nt via direct synthesis?
Because making oligos longer than 200 nt suggests to a large margin of error. The process is already error prone as a single cycle is not at 100% efficiency, this lessens the yield as the sequences get longer.
Why cant you make a 2000bp gene via direct oligo synthesis?
At this stage of developing oligo synthesis, the current limit is 700 nucleotides.
[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”?
Lysine, leucine, isoleucine, valine, threonine, methionine, phenylalanine, tryptophan, histidine, arginine.
The lysine contingency leverages animals’ reliance on lysine. While it is plausible, given that animals need it for survival. But it is highly unlikely that the dinosaurs (animals) wouldn’t find it available in their environment given how readily available it is in the ecosystem. My biggest issue with this idea is that lysine absence (again, farfetched) would take weeks before the animal dies from it.