Homework
Weekly homework submissions:
Week 1 HW: Principles and Practices
Question 1: A biologically engineered application that I find particularly compelling is the development of gene editing tools for biodiversity conservation. Given the rapid global decline of many species driven by human activity, emerging infectious diseases, and climate change, preserving biodiversity and maintaining ecosystem stability has become an urgent scientific and societal challenge. One promising application of genetic engineering in this context is the germline editing of amphibian genomes to combat the chytrid fungus, Batrachochytrium dendrobatidis, which has caused widespread population declines and driven numerous frog and toad species toward extinction.
Homework Part A: General and Lecturer-Specific Questions General homework questions Explain the main advantages of cell-free protein synthesis over traditional in vivo methods, specifically in terms of flexibility and control over experimental variables. Name at least two cases where cell-free expression is more beneficial than cell production. Cell-free protein synthesis removes the constraints we usually face for protein synthesis when working with live cells. For example, working with live cells requires culturing cells throughout the whole cell lifecycle, with all the possibilities for error that this implies (mistakes, unexpected cell behavior due to their non-deterministic nature, etc), as well as the required timelines (speed is limited by the fundamental speed constraints from the cell growth cycle), and costs. Cell-free systems also allow for much greater control, as the main system is boiled down to its most basic functional components, removing a lot of complexity (variables outside of our control), and therefore allowing the possibility of producing much more homogeneous products.
Week 2 HW: DNA Read, Write, Edit
Week 2 Pre-Lecure Homework: Homework Questions from Professor Jacobson: 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? DNA polymerase makes about 1 error per 10⁴ bases during replication. Since the human genome is about 3 billion base pairs, this would result in roughly 300,000 errors per replication if left uncorrected. Biology handles this through proofreading and DNA repair systems, which dramatically reduce the final number of mistakes.
HTGAA Week 03 - Lab Automation Find and describe a published paper that utilizes the Opentrons or an automation tool to achieve novel biological applications. https://www.nature.com/articles/s42003-019-0305-x?utm_source=chatgpt.com This paper used a Tecan liquid handler to enable high-throughput patient-derived tumor organoid drug screening, moving beyond pipetting into a biologically novel precision medicine application. The researchers wanted to determine whether patient-derived tumor organoids (miniature 3D tumors grown from real patient cancer tissue) could be used to rapidly identify effective anti-cancer drugs for individual patients. The Tecan system automated several otherwise tedious and error-prone steps: precise dispensing of organoid cultures into multiwell plates, automated addition of large drug libraries at multiple concentrations, and standardization of timing and reagent handling to reduce variability between samples. This helped make organoid-based drug screening much more scalable as a workflow for research.
Week 04 - Protein Design I Part A How many molecules of amino acids do you take with a piece of 500 grams of meat? (on average an amino acid is ~100 Daltons) 6.6 x 1023 molecules of amino acids Why do humans eat beef but do not become a cow, eat fish but do not become fish?
Part A: Generate Binders with PepMLM Begin by retrieving the human SOD1 sequence from UniProt (P00441) and introducing the A4V mutation. Sequence with mutation: MATKVVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTS AGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVV HEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ Using the PepMLM Colab linked from the HuggingFace PepMLM-650M model card: Generate four peptides of length 12 amino acids conditioned on the mutant SOD1 sequence. WRYYAAALRHKG WRYYAVAARHKK WRSYVVVLELGG HHYPAVAVALKG FLYRWLPSRRGG To your generated list, add the known SOD1-binding peptide FLYRWLPSRRGG for comparison. Part B