Homework
Weekly homework submissions:
Week 1 HW: Principles and Practices
- Describe a biological engineering application or tool you want to develop and why? Answer: I want to design a ligand gated episomal system which relies on a synthetic promoter that is designed to trigger expression in the presence of a specific external molecule. Detection of this molecule is done by a modified unused cell pathway, which detects an external molecule and activate the synthetic promoter present in the non integrating episome. In this architecture, the expression is not constitutive or always on. Instead the modified cell remains inactive unless the engineered molecule binds to the modified receptor. This creates a programmable ON-switch that enables control over the activation. It matters as the episomal design allows reversable and tunable gene expression without permenant genomic integration which prevents many of the off target effects and possibly do awsome things like generating plants that can glow in dark or various gene therapies in humans or animals. 2. 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. Answer: Goal A: Activation Reliability and Biological Safety Sub Goals A1: Prevent Unintended Activation A2: Ensure there is a reliable OFF Control Goal B: Transparency and Clinical Oversight Sub Goals B1: Maintain interpretability of Genetic Control Logic B2: Support long term monitoring of engineered cell behavior especially in immunotherapies Goal C: Misuse Prevention and Responsible Innovation Sub Goals C1: Prevent Unauthorised triggering C2: Promote Secure development and deployement practices 3. Describe at least three different potential governance “actions” by considering the four aspects below (Purpose, Design, Assumptions, Risks of Failure & “Success”) Answer: Option 1: Make reliability testing mandatory for ligand-gated systems Purpose: Right now, engineered systems are mostly evaluated for general safety. Here, since activation depends on a specific ligand, we need to make sure the system does not accidentally turn ON. So the purpose is to make reliability testing of the ON-switch compulsory.
Week 2 HW: DNA Read Write and Edit
Week 1 Lecture Prep Homework Questions from Professor Jacobson 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? Answer: DNA polymerases with proofreading (like human replicative polymerases) have an intrinsic error rate of approximately 10⁻⁶ to 10⁻⁷ errors per base per replication. After mismatch repair, the final in vivo mutation rate is approximately 10⁻⁹ to 10⁻¹⁰ per base per cell division. The human genome is ~3.2 × 10⁹ base pairs. If replication occurred at 10⁻⁶ error rate without repair, it causes 3 × 10⁹ bp × 10⁻⁶ ≈ ~3,000 mutations per cell division. But observed mutation rates are closer to ~0.1–1 mutations per genome per division. Biology resolves this discrepancy by using a layered fidelity systems which includes, Base selectivity of polymerase, 3’ - 5’ exonuclease proofreading, DNA damage repair pathways and Mismatch repair (MMR) system. Together these reduce the errors.