Homework
Weekly homework submissions:
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. Currently, I develop software that creates new paradigms of computer-aided design (CAD) for systems that don’t fit conventional models of making. For example, most current mainstream CAD applications rely on drawing and volumetric representation as the main mechanism of formal shape creation. However, with newer fabrication systems such as robotic printing, zero-gravity printing, pigment printing, and other digital manufacturing advances, the tooling for operating this hardware lags behind the creation potential of these machines.
Homework Questions from Professor Jacobson: [Lecture 2 slides] 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? 1 error per 106 additions, with a throughput of 10 mS per Base Addition. If a human genome is 3.1 gigabase pairs haploid, then 3.1 109 / 10 6 = 3100 errors (3.1 * 1000) It fixes these errors during biological synthesis, where the nucleotides in an error physically dont fit together so it pushes that error out to unjam the system and continue on with further synthesis 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? 1036 base pairs in an average human protein, 3 bp (codon) per protein = 1036 / 3 = ~345 3345 That’s a huge number, but these dont all work physically because of codon bias, mRNA structure, regulatory interference, and translation/folding constraints. Note: Had to ChatGPT this one “Why don’t all codon possibilities work at a protein site?, couldn’t find it in the slides. Homework Questions from Dr. LeProust: [Lecture 2 slides] What’s the most commonly used method for oligo synthesis currently? 1965 Solid phase synthesis of oligos Had to search google separately Why is it difficult to make oligos longer than 200nt via direct synthesis? Because errors accumulate over time, even though oligo synthesis has a 99% success rate, the 1% error rate over time breaks it down with the step-by-step addition. So at 200 nucleotide length, you get a 37% full length molecules, which you can purify away from the rest. Beyond this, the exponential rate of the error makes it not wort the amount of effort. Why can’t you make a 2000bp gene via direct oligo synthesis? A looped run with error rate 99.5% 2000 times == 0.000045 chance of success, because oligo synthesis is all or nothing once a failure occurs. Homework Question from George Church: [Lecture 2 slides] Choose ONE of the following three questions to answer; and please cite AI prompts or paper citations used, if any.
Part 1 Benchling Part 2 Lab Notes: Restriction Digest and Gel Electrophoresis Overview We’re cutting Lambda DNA with different restriction enzymes to create patterns in an agarose gel (inspired by the Latent Figure Protocol). The ladder helps us visualize the DNA fragment sizes based on base pair length.
Part 1 Find and describe a published paper that utilizes the Opentrons or an automation tool to achieve novel biological applications. Vespers III The paper presents a fabrication platform for making 3D-printed objects whose surfaces host living bacteria that respond to chemical signals embedded in the print material. The central idea is that a multimaterial inkjet printer can be used not just to control mechanical properties, but to spatially distribute chemical inducers throughout an object — and that bacteria coated onto the surface will “read” those signals and express proteins accordingly. The printer they used (Stratasys Objet Connex500) normally blends a rigid build resin with a sacrificial support resin to handle overhangs. The authors noticed that the support resin (SUP705) is hygroscopic — it absorbs water — which makes it useful for soaking up and slowly releasing chemical solutions like IPTG. By controlling how much support resin appears in each voxel, they could tune how much inducer gets released at any given spot on the surface. Later in the paper they go further and dissolve inducers directly into custom resin formulations loaded into the print cartridges, which lets them place two different chemical signals (IPTG and AHL) independently during a single print job. Bacteria are delivered by spraying a warm hydrogel-cell mixture onto the surface, which gels on contact. The hydrogel keeps cells alive, feeds them, and lets the inducers diffuse through from the print material below. Depending on what genetic circuits the cells carry, they produce visible outputs — blue or magenta pigment via β-galactosidase activity, or fluorescent proteins. The team also tested cells with AND and NAND logic gates, so expression only occurs where both signals are present, or where neither is. They built a computational model to predict how signals diffuse across 3D surfaces over time and how bacteria respond, which they validated against experimental results. The match was reasonable in most regions but broke down close to high-concentration signal sources, partly because some material compositions turned out to lower local pH and suppress expression — something the model didn’t account for.
Part A Why humans eat beef but do not become a cow, eat fish but do not become fish? Part B: Protein Analysis and Visualization In this part of the homework, you will be using online resources and 3D visualization software to answer questions about proteins. Pick any protein (from any organism) of your interest that has a 3D structure and answer the following questions.