Week 1 HW: Pre-Prep Week 2
- 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?
The error rate of polymerases depends on their type, as Human DNA has mechanisms for proofreading that other organisms’ DNA lacks. The error rate for DNA polymerase is 1 in every 107 base pairs. As compared to the human genome size of 6 X 109 base pairs. The mechanisms include mismatch repair, base excision repair, nucleotide excision repair, NHEJ, HR, damage checkpoint, and some tolerance mechanisms. This is how biology deals with discrepancies via multiple mechanism before-during-after DNA replication and the cell cycle.
Prompts - What is the length of human DNA base pairs? what the different ways in which DNA is proffread nd repaired?
- 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?
As each amino acid has 3 codons mostly and proteins are made of a combination of 20 amino acids. With a lot of amino acids with multiple codons , the ways to code are astronomically huge.
Codes at times fail to work as the amino acids might not form the protein folding form, mRNA fold, tRNA, ribosome as the same ones required in the cells. That is where protein design and coding gets complex to gain the exact intended expression.
https://doi.org/10.3390/biom14010132
- What’s the most commonly used method for oligo synthesis currently?
phosphoramidite chemistry
- Why is it difficult to make oligos longer than 200nt via direct synthesis?
As error accumulates on every nucleotide addition , so instead assembling enzymatically i better.
- Why can’t you make a 2000bp gene via direct oligo synthesis?
Again error rates decrease final yields and limit purification, which also leads to yield loss.
10 AA in animals and What do you think about Lysine Contingency?
The ten essential amino acids in animals are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and arginine;
“lysine contingency” means the biological dependence of animals on external lysine supply due to the absence of lysine biosynthetic pathways. This creates a dependency that can be exploited in evolution and synthetic biology for metabolic control and biocontainment.
My take on Lysine Contingency is - This can certainly be a powerful tool to implement biocontainment when we decide to inhabit or spread bioforms on extraterrestrial land. But it also threatens the very existence of human & animal bodies, in turn showing our dependency on plants. It certainly makes me further appreciate the importance of the food chain and the evolutionary process of life forms.
Prompts : 10 amino acids in all Animals? What does Lysine Contingency mean?
Week 1 HW: Principles and Practices
- 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.
As I have been thinking about the different ways synthetic biology can help with menstruation and its complexities (painful, irregular bleeding) when it comes to people with PCOS and endometriosis. I want to develop an autonomous endometrial gene circuit that senses estrogen or progesterone peaks and locally regulates endometrial growth. The goal is non-hormonal, reversible control of menstrual bleeding, which could prevent heavy bleeding or abnormal endometrial proliferation while minimizing systemic hormone exposure.
WHY - Hormonal regulation comes with lots of cons, and in general, having control over the reproductive cycle can benefit the population and quality of life overall.
During iGEM Startups 2024, I worked theoretically on Femflux, an aptamer biosensor that analyzes interstitial fluid to analyze estrogen and later predicts & helps peri-menopausal women. I realised that as people experiencing menstrual cycles, we have little to no control over it, despite it affecting us beyond reproduction. While interviewing multiple indian women, a common answer towards the want to use a product like this was- WHY? As if the choice to prevent or help our health is not enough of a reason to want tech development. The answers were sad, showing the priority of healthtech use for them was an afterthought, unnecessary even.
So, I would ike to explore beyond current methods for controlling bleeding (hormonal contraception, surgery) that are either systemic or irreversible. The power to bring back control and want.
This system could give women personalized, cycle-specific control with minimal side effects.
It could also integrate with broader synthetic biology tools like hormone biosensors and predictive health platforms, potentially linking to osteoporosis prevention or menopause health monitoring.
- 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).
Main Goal: Ensure the autonomous endometrial synthetic switch is safe, ethical, equitable, and respects women’s autonomy, while minimizing potential misuse or exploitation.
Safety & Non-Malfeasance
Prevent off-target gene silencing outside the endometrium.
Ensure reversibility and prevent long-term adverse effects.
Equity, Autonomy & Access Control
Ensure that women can choose whether to use the system themselves.
Prevent exploitation by third parties (e.g., coercive use by healthcare providers, employers, insurers).
Protect patient privacy and decision-making authority.
Research Transparency & Constructive Use
Encourage safe development and sharing of protocols to advance science while preventing misuse
2/. Next, describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”).
| Action | Purpose | Design | Assumptions | Risks of Failure / Success |
|---|
| 1. Regulatory preclinical & access control standards | Require regulators (FDA/EMA) to define safety, reversibility, and who is authorized to deploy the technology | Regulatory bodies set licensing/approval frameworks; companies must enforce access restrictions; independent review boards certify compliance | Assumes regulators can define enforceable access rules; assumes compliance can be monitored | Failure: Unauthorized use or coercion; Success: Safe, controlled rollout, preserves trust but may slow commercialization |
| 2. Technical transparency & misuse prevention | Require labs and companies to maintain secure registries of who is authorized to develop or deploy circuits | Secure, monitored databases; access limited to trained personnel; funding agencies enforce compliance | Assumes secure systems and proper auditing; assumes actors cannot bypass rules | Failure: Data leaks or misuse; Success: Protects women from exploitation while promoting constructive research |
| 3. Ethical consent, autonomy & personal use option | Establish mandatory consent standards and enable women to opt-in for personal, self-controlled use | IRBs, hospitals, and companies collaborate on clear informed consent protocols; include options for women to use devices under medical guidance or self-use frameworks | Assumes patients understand synthetic biology complexity; assumes autonomous use is technically feasible | Failure: Misunderstanding or misuse; Success: Empowers women, prevents coercion, ensures autonomy |
- Next, score (from 1-3 with, 1 as the best, or n/a) each of your governance actions against your rubric of policy goals.
| Policy Goal | Criteria | Regulatory Preclinical & Access | Technical Transparency | Ethical Consent & Self-Use |
|---|
| Safety & Non-Malfeasance | Prevent off-target effects, ensure reversibility | 1 – Strong, enforced by regulators | 2 – Moderate, improves safety indirectly | 2 – Moderate, relies on user understanding |
| Autonomy & Access Control | Preserves user choice, prevents exploitation | 1 – High, access rules controlled | 2 – Moderate, indirectly supports | 1 – Strong, women can choose use |
| Equity & Ethical Use | Fair access, informed decisions | 2 – Moderate, access may favor regulated regions | 2 – Moderate, depends on compliance | 1 – Strong, empowers women directly |
| Constructive Innovation & Research Integrity | Encourages transparency, reproducibility | 2 – Moderate, strict rules may slow innovation | 1 – Strong, promotes reproducible research | 1 – Strong, supports ethical, constructive use |
| Feasibility & Practicality | Cost-effective, scalable, technically implementable | 2 – Feasible but adds regulatory burden | 2 – Feasible with moderate cost | 1 – Feasible, can be implemented with clear protocols |
Prioritize:
Primary: Ethical Consent, Autonomy & Self-Use (most directly protects women, prevents exploitation).
Secondary: Regulatory Preclinical (ensures safety).
Trade-offs:
- Assumes users can understand synthetic biology risks; additional education required.
Audience:
FDA / EMA: Set safety, reversibility, and access rules
Academic & Industry Labs: Comply with transparency and security standards
Hospitals / Patient Advocacy Groups: Implement consent and self-use protocols
Johns Hopkins Medicine Researchers Find Early Success Using Endometrial mRNA Therapy to Treat Infertility | Johns Hopkins Medicine
Hormonal control of Menstrual bleeding https://www.youtube.com/watch?v=5q4ExatWfUU
Femflux https://docs.google.com/presentation/d/1Ew0E1LpoUeQWVf2WQQrztRrIYIA44LLRTVOx55lRuIE/edit?usp=sharing
