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Molecular Bio + Nanotech

DNA + RNA Overview

  • DNA is the storage of biology. DNA is double stranded with each strand being the corresponding opposite of the other. This acts as a backup mechanism for if one strand gets damaged the other can direct the repair and no information is lost. Since there are two strands one separate to act as a template in the synthesis of a new DNA strand via enzymes called DNA polymerases.
    • We started in an RNA world that evolved to DNA as DNA provided a more stable genetic material that facilitated the evolution of higher complexity organisms.
    • One end of the DNA is 3' and the other 5'. Polymerases can only add on to the 3' end.
    • Genes are only by RNA polymerases 5'-3'. RNA polymerases knows where tp start transcribing a gene bc it interacts with the promoter, a stretch of DNA upstream on the 5' side of the gene. RNA polymerase binds the promoter before it begins transcription.
    • Replication is initiated by the primase enzyme, which synthesises a short RNA primer.
    • The polymerase chain reaction (PCR) is how we can duplicate DNA artifically w/ a PCR machine.
  • RNA, specifically messenger RNA (mRNA) is the calldata to create proteins which carry out functions within the cell.
    • DNA is transcipted into RNA, via RNA polymerase, which is then translated, as transfer RNA (tRNA), into protein.
    • It takes the “message” to the ribosome where the nucleotides are turned into amino acids (the building blocks of proteins)

MicroRNA

MicroRNA (miRNA)

Biochemistry

Molecular biology is an interdisciplinary field that relies heavily on chemistry. And so biochemistry provides the foundational knowledge required to understand molecular biology fully. We’ll be looking deeper into organic chemsitry though, the study of molecules with carbon in them. It explains the chemical interactions and reactions that underpin the structure and function of biomolecules. When observing the reason why enzyems cut, DNA replicates, transcripts, translates, molecules bind and everything “functioning” the underyling causes are chemical reactions. Chemistry is the bridge to understanding these interactions. The formation of proteins and everything else is simply chemistry!

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Nucleotides

There are 4 nucleotides, [A, T, C, G] in DNA and [A, U, C, G] in RNA, and by themselves they cannot create 20 different types of combinations. However, biology has created codons which are sets of 3 nucleotides, e.g. AAA, ACA, etc, therefore we can create 43=644^3 = 64 combinations.

  • 61 codons specify amino acids.
  • 3 codons (UAG, UGA, and UAA) are stop codons, which signal the ribosome to to release the newly synthesized polypeptide chain from protein synthesis. The reason there isn’t DNA stop codons is bc translation occurs in messenger RNA (mRNA) and so Thymine (T) is substituated for Uracil (U). DNA serves as the template for RNA synthesis during transcription.

If any nucleotide mutates in a sequence then it can result in a large change. As an analogy we can change a single bit in your bank balance:

What we wanted to decode 1

000 000 000 000 000 001

But we decoded 1e17

100 000 000 000 000 000

Or even decoding the wrong bit for the correct position. Instead of true we decoded false that may have the same effect.

000 000 000 000 000 000

Imagine this single bit mutation in an organism that results in more wings, taller, etc.

Molecular programming would be having a compiler that sends this compiled ACTG code to a DNA synthesiser to create the molecules. Then you could create a big program repo w/ different aspects: [ribosome.rna, t_cell.rna, etc].

If you can create program computation into RNA and build some kind of circuit with for loops, etc, then you can probably program anything into RNA.

Amino Acids

There are 20 amino acids which form proteins. Nearly every single job in the cell is performed by a protein. They are the jack-of-all-trades.

When proteins are placed in water they twist and fold, finding an optimal shape that will shelter the hydrophobic amino acids inside and display the charged amino acids on the surface. The final shape of the folded protein is completely predetermined by the order of amino acids in the protein chain.

  1. Arginine
  2. Lysine
  3. Aspartate
  4. Glutamate
  5. Asparagine
  6. Glutamine
  7. Cysteine
  8. Methionine
  9. Histidine
  10. Serine
  11. Threonine
  12. Valine
  13. Leucine
  14. Isoleucine
  15. Phenylalanine
  16. Tyrosine
  17. Tryptophan
  18. Glycine
  19. Alanine
  20. Proline

The physical matching of each nucleotide triplet with its proper amino acid is performed by **transfer RNA (tRNA). There are 20 different types of tRNA molecules made w/ the different triplet of nucleotides at once end, called anticodons, and the corresponding amino acid attached at the other end.

20 different enzymes load the proper amino acid onto each type of tRNA.

Ribosomes bring everything together to build the rteoin. At a rate of about 20 amino acids per second, an average protein takes about 20 seconds to build.

You can mae an entirely new proteins by modifying the instructions in the genome. The protein synthesis machinery builds it for you.

Some instructions are essentially hardcoded because they’re so valuable. For example, the enzyme glyceralde-hyde-3-phosphate dehydrogenase is virtually identical in human cells and in becteria. Other proteins are remodeled every day, e.g. our antibody genes are edited to create new, fine-tuned antibodies to attack new infections. I think of this as a spectrum of “how useful is this to keep vs modify” and it seems that all agents in evolution try to “keep” as many of the useful ones as possible and explore the search space for new ones in new generations.

Mutations

Protein mutations happen via ribosome translation.

Genome mutations happen in the nucleus for eukaryotes and the nucleoid region of the cytoplasm for prokaryotes during DNA replication via DNA polymerase. DNA replication is how organisms pass on their genetic information to daughter cells during cell division. So if its replicated with an error and the correction system is faulty then it remains.

Mutations in non-reproductive cells (somatic cells) may lead to cellular dysfunction, uncontrolled cell growth (cancer) or cell death.

Mutations in reproductive cells (germ cells) like sperm or egg can cause offspring to inherit those variations, introducing potentially advantageous traits to contribute to evolution.

Point Mutations

  • Substitutions: A single base pair is replaced by another (e.g. A→G). This can be a transition (purine→purine or pyrimidine→pyrimidine) or a transversion (purine→pyrimidine or vice versa).

Substitutions can lead to:

  • silent mutations: no change in amino acid
  • missense mutations: different amino acid
  • nonsense mutations: premature stop codon

Insertions

One or more extra base pairs are inserted into the DNA sequence.

Deletions

One or more base pairs are deleted from the DNA sequence.

Frameshifts

Insertions or deletions that are not a multiple of 3 bases, causing a shift in the reading frame of codons during translation.

Repeted Expansions

Increase in the number of repeated copies of the same codon, resulting in repeated amino acid sequences.

Large-Scale Mutations

  • Copy number variations (CNVs): Insertions, deletions or duplications of large DNA segments.
  • Inversions: A segment of DNA is reversed in orientation.
  • Translocations: Segments of DNA move from one location to another, within or between chromosomes.
  • Aneuploidy: Gain or loss of entire chromosomes.

Bacteria

Fungus

Slime mold is a protozoan, meaning its a single-celled Eukaryote able to push the boundaries of it’s one cell further and further.

Mold is super interesting because they start as the small spore it expand in the form of threads called hyphae. Sometimes they form branches of their own or fuse with one another creating a web of hyphae called mycelium. This network acts as a feeding apparatus. The hyphae will secrete enzymes into the medium around it, breaking down it’s nutriants so that fungus can eat. It’s basically a really large network of mouths.

Whats even more interesting is that fungi can eat a shit load of things. There are fungi is Chernobyl eating away at radioactive material, like hot graphite.

Viruses

Viruses aren’t actually alive. They’re non-living particles that entire depend on host cells as they don’t reproduce outside of living cells! These are the parasites of the microcosmos that leech off their host’s resources to survive.

They range from sizes 0.02 to 0.25 microns, making most viruses submicroscopic (which is why electron microscope is used to observe them).

The infections are systematic, spreading throughout the entire body. The scary part is that viruses can reprogram the host cells, mainly for reproduction, oftening causing the infected cell to die.

There are three types of viruses

RNA Viruses

These contain RNA as their genetic material to inject into the cell and replicate by producing new viral RNA using their own RNA-dependent RNA polymerase enzyme. The RNA stand is inherintly less stable and has a higher mutation rate than DNA since there is no backup strand for proofreading if it gets damaged.

When DNA cells replicate their DNA they use DNA polymerases enzymes that proofread and fix any mistakes made during the copying process, like an audit. RNA viruses replicate their genomes using an RNA-dependent RNA polymerase (RdRp) enzyme which lack efficient proofreading mechanisms to remove typo nucleotides (the building blocks of RNA), e.g. A instead of G. Therefore these typos are what casues the mutation and there is no “spell-checker” to fix them. Its estimated to be around 1 mutation per 10,000 to 100,000 nucleotides copied for RNA viruses and the RNA virus genome sizes range from around 3,000 to 30,000 nucleotides.

DNA viruses mutate around 10−610^{-6} to 10−810^{-8} per base per generation/replication cycle whereas RNA viruses mutatate at around 10−310^{-3} to 10−610^{-6}. This means RNA viruses is around 2-4 orders of magnitude aka 100-10,000 times higher than DNA viruses.

Retroviruses

Just like normal RNA viruses, they inject RNA into the cell. However, it uses an the reverse transcriptase (RT) enzyme to convert the RNA into DNA that later is tried to integrate into the host cell’s genome as a provirus (injecting genetic material into the genome of the host it infects). This is why is so incredibly hard to cure these because you need to know what changed in your genome to be able to identify where it is. Luckily, they don’t replicate into other parts of the genome, it’s just a single injection somewhere in the genome. But, it is replicated passively with the host cell’s DNA during cell division. This means all daughter cells will contain the integrated proviral DNA copy. This makes it invisible to detect and is why something like HIV is so deadly.

DNA Viruses

These contain double-stranded DNA to “save a copy” of their virus if one strand gets damaged since there are proof mechanisms in place. This results in less frequent mutations, meaning it evolves much slower than RNA viruses. It’s not a glass-cannon like the other two RNA ones. It simply replicates in the cell host’s machinery to produce more viral DNA and proteins. Since DNA is a storage device it is able to establish latent infections and reactivate later, e.g. Herpesviruses.

Since these evolve so slowly, it’s quite interesting how the Herpesviruses have not been cured since making a vaccine is significantly more feasible than RNA viruses. Probs bc the lack of threat and free money involved from Pharma companies is my guess.

Transmission

Bloodborne

The most common way would be through fluids such as saliva or blood. Whenever you get a cut or pricked by a neelde it’s then transmitted via the blood stream to get to the cells it needs.

Vectorborne

Vectors like insects (mosquitoes) act as the gataeway to the body during a blood meal. It’s essentially being bloodborne with an active aggressor that initiates the transmission whereas only bloodborne would be the

Airborne

Viruses become airborne when they’re able to remain suspended in the air via respiratory droplets.

Large droplets are generally defined as >5-10 micrometers (μm) in diameter and are primarily responsible for short-range transmission as they tend to settle quickly bc of gravity. These droplets are generated during coughing (8-32 μm), sneezing, or talking.

The smaller the droplet the longer it remains airborne and cna travel further distances. The most dangerous ones are <5 μm, especially <1 μm bc they have a high likelihood of going deep into the respiratory tract — these sizes come from breathing and the others form large droplets.

Biological weapons possess destructive potential and loss of life far in excess of nuclear, chemical or conventional weapons. An airborne virus would be incredibly powerful and would have the potential to wipe out humanity without anyone even seeing it.

Molecular nanotechnology (MNT)

  • Can cure death or at minimum fight viruses and bacteria.
  • Modify molecules, atoms, on-the-fly chemistry within the body and outside of it
  • Is the robotics field of molecular biology, e.g. ribosomes.
  • Used in parallel with AI + molecular bio

Mechanosynthesis is machine-controlled construction of complex molecular products by controlling individual molecular reactions. The chemical syntheses by mechanical constraints to direct reactive molecules to specific molecular sites. There are no non-biological chemical syntheses that can do this, yet. The ribosome is an example of a programmable mechanosynthetic device.

What if nanotech starts small and then builds itself by reorganising atoms? e.g. nanotech bacteria that becomes multicellular (multiple nanobots) then builds itself via that, just as bacteria.

MNT provides the hardware for the better computer, for light stronger materials, better medical technology.

Space becomes accessible by nanotech. If you able to make materials such as diamond thats 50:1 strength to weight of steel then its the single invention that changes all possibilities bc the flagpost of constraints are pushed considerably.

Self Assembling

Molecular Machines

Seeds

Ribosomes

Kinesins

motor proteins, kinesin (“kin-EE-sin”) — proteins are really where it’s at - actual molecular machines.

Microtubules

are self-assembling highways that Kinesin walk on to carry proteins around in the cell and also separates chromosomes during cell division

Resources