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?
Polymerase has an error rate that ranges from about 1 in 10,000 to 1 in a million. While this may seem like a lot, the human genome is made up of approximately 3 billion base pairs, meaning that errors in replication could accumulate quickly. But biology has its own solution: it uses various proofreading mechanisms built into the polymerase, as well as repair systems like the MutS complex, which catch and correct mistakes during the replication process, ensuring that the genome stays accurate over time despite the occasional slip-up.
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?
When we talk about how many different ways we can code for an average human protein, there are multiple codons that can encode the same amino acid, thanks to the redundancy in the genetic code. This means that the system has a bit of flexibility in how proteins are made. But not all these possible codons are equally efficient. Some codons are preferred over others. It’s like a game of chess, where there are many possible moves, but certain ones are more likely to lead to victory. In this case, a properly folded and functional protein.
Questions from Dr LeProust
What’s the most commonly used method for oligo synthesis currently?
I believe that the most commonly used method is phosphoramidite chemistry. A method based in the coupling of nucleotides to a growing chain of DNA, followed by oxidation, capping unreacted sites, and deblocking, with each step repeated in cycles
Why is it difficult to make oligos longer than 200nt via direct synthesis?
Is difficult due to issues of error accumulation and yield loss.
Why can’t you make a 2000bp gene via direct oligo synthesis?
For long sequences such that, the error rate is too high, leading to incomplete or incorrect sequences. Also, the cost and time required is really high, so it is not suitable for such synthesis.
Questions from George Church
What are the 10 essential amino acids in all animals and how does this affect your view of the “Lysine Contingency”?
The 10 essential amino acids are Arginine (Arg), Histidine (His), Methionine (Met), Isoleucine (Ile), Leucine (Leu), Lysine (Lys), Phenylalanine (Phe), Threonine (Thr), Tryptophan (Trp), and Valine (Val). Their are called essential because animals cannot synthesize and we have to obtain them in the diet. The Lysine Contingency, introduced in Jurassic Park, makes no sanse from that point of view. This is a genetic mechanism that is supposed to make dinasours dependent to substances including lysine. However in real life, any animal is capable to produce lysine. Herbivores obtain lysine from plants, and carnivores obtain lysine by eating other herbivores. In the movie, dinasours are capable of eating other animals, or humans, so the lysine contingency would apply.
What code would you suggest for AA:AA interactions?
I would propose a simple sistem using the three letters name of the AA, the simbol (-) to represent the bond and the name of the other AA, e.g Lau-Lys. Another sistem would be mapping each of the 20 AA to single-letter codes (A-Z). This sistem also allows to subdive other charactarestics of the AA such as Nonpolar/Hydrophobic, Polar/Uncharged, Acidic/Basic behavior.
Given the one paragraph abstracts for these real 2026 grant programs sketch a response to one of them or devise one of your own:
BioStabilization Systems recovered from https://arpa-h.gov/explore-funding/programs/boss. I am particularly interested in stabilization. In my thesis project I delved into the topic of nanoparticle stabilization in polymer matrices. Following that, I had the opportunity to participate in the mini-symposium “Bacteriophages in Science and in Practice,” organized by the Institute of Biochemistry and Biophysics PAS. One of the talks addressed the stabilization of phages in natural extracts such as essential oils and in polymers like gelatin. I really liked this approach because I believe that the solution to stabilizing chemical systems (nanoparticles stabilized in a colloidal polymer solution) or biological systems (phages in a buffer with a polymer or extract) is closely linked to materials science. Personally, I’m interested in green synthesis and natural extracts, so I would propose a stabilization method using ideas from these areas. I would propose an experiment with different buffers: one with SM Buffer, another with SM + Natural Extract, and another with SM + Natural Extract + Biocompatible Polymer, and evaluate phage production in each.