Ciro Santilli believes that molecular biology technologies will be a large part of the next big things as shown at: Section "Molecular biology technologies".
Bibliography:
- https://www.youtube.com/watch?v=mS563_Teges&list=PLQbPquAyEw4dQ3zOLrdS1eF_KJJbUUyBx Biophysical Techniques Course 2022 by the MRC Laboratory of Molecular Biology. Holy crap that playlist is a tour de force of molecular biology techniques in 2022!
Study of the metabolome.
Examples:
For a commented initial example, see: e. Coli K-12 MG1655 gene thrA.
KEGG does the visual maps well.
But BioCyc is generally better otherwise.
An artificial metabolic pathway using synthetic biology technology.
Design software for synthetic biological circuit.
The input is in Verilog! Overkill?
Then it essentially maps to a standard cell library of biological primitives!
It is quite cool that photosynthesis works just like cellular respiration by producing a proton potential through chemiosmoses.
https://www.youtube.com/watch?v=4HxqQOHifkU&list=PLGlvFEwL2wDGAFJFFFyi-LL1zu64BHvxv Cell Culture Basics playlist by Thermo Fisher Scientific. Content on their website: https://www.thermofisher.com/uk/en/home/references/gibco-cell-culture-basics.html
Power, Sex, Suicide by Nick Lane (2006) part 5 "Murder or suicide" mentions that apoptosis has two main functions:
- prevent cancer
- but it is also an important part of body development, e.g. fingers are separated because cells between them kill themselves. Otherwise we would have webbed feet like ducks. There is also a lot of apoptosis during the development of the brain. This has been observed notably in C. elegans see also: Section "C. elegans cell lineage".
Power, Sex, Suicide by Nick Lane (2006) part 5 "Murder or suicide" mentions that the key events that leads to apoptoses is when certain proteints normally present in the inner mitochondrial membrane spill out, and that this often happens when free radicals are produced in excess: the cell is really not doing well in those cases. This point suggests that the initial mitochondrial endosymbioses happened due to a parasite that lived inside another cell. It mentions that even today we see parasites kill the host cell when they feel that the cell does not have many nutrients. This frees the parasites to then infect other cells.
Types:
One major advantage: eukaryotes can do phatocytosis due to their cytoskeleton.
Opposed to the hydrogen hypothesis, in which both cells cooperated from the start.
https://pubmed.ncbi.nlm.nih.gov/27185558/ A Eukaryote without a Mitochondrial Organelle by Karnkowska et. al (2016)
As of 2020, there are no known eukaryotes which have never had mitochondria.
Known eukaryotes without mitochondria, which are very rare, have lost mitochondria they previously had.
Having mitochondria appears to be a requisite for being an eukaryote. This is one of the central thesis of Power, Sex, Suicide by Nick Lane (2006).
Space inside inner mitochondrial membrane.
Space inside the outer mitochondrial membrane but outside the inner mitochondrial membrane.
Notably, it does not undergo crossover.
It has to swim fast, right!
So how is it that mitochondria are not inherited from the father?
- 2016 https://www.sciencedaily.com/releases/2016/06/160623145932.htm It appears that the exact mechanism hadn't been elucidated
These have almost certainly been transferred to nuclear DNA in the course of evolution.
This isn't completely surprising, since when mitochondria die, their DNA is kind of left in the cell, so it is not hard to imagine how genes end up getting uptaken by the nucleus.
A limiting factor appears to be that you can't just past those genes in the nucleus, further mutations are necessary for mitochondrial protein import to work, apparenty some kind of tagging with extra amino acids.
However, you likely don't want to remove all genes from the mitochondria because mitochondria have DNA because they need to be controlled individually.
The process that imports proteins encoded in the nuclear DNA and made in the cytosol into the mitochondria.
The term is mentioned e.g. in this article: https://www.nature.com/articles/nrm2959.
Power, Sex, Suicide by Nick Lane (2006) suggests that proteins are somehow tagged with extra amino acids for this.
Argued at Power, Sex, Suicide by Nick Lane (2006) page 212.
Basically, energy supply has to be modulated rather quickly, because we spend a lot sometimes, and very little other times.
Even not turning it off quickly enough is a problem, as it starts to generate free radicals which fuck you up.
If control came from the nucleus, it has no way to address different mitochondria. But it might be that only one of the mitochondria needs the change. If the nucleus tells all mitochondria to stop producing when only one is full, the others are going to say: "nope, I'm not full, continue producing!" and the one that need to stop will have its signal overriden by the others.
DNA stuff at: human mtDNA.
All pages below are from the second edition from 2018. It seems that there weren't any changes in the text, the updated preface mentions
As it happens, nearly 15 years have passed since the 1st edition of Power, Sex, Suicide was published, and I am resisting the temptation to make any lame revisions. Some say that even Darwin lessened the power of his arguments in the Origin of Species through his multiple revisions, in which he dealt with criticisms and sometimes shifted his views in the wrong direction. I prefer my original to speak for itself, even if it turns out to be wrong.
This is partly addressed in the preface of the second edition from 2018.
Central thesis:
- there are two sexes because of mitochondria
- the acquisition of mitochondria was one of the most important steps in the evolution of eukaryotes.There are no known eukaryotes which never had mitochondria. Having mitochondria appears to be a requisite for being an eukaryote.Contrast this for example with multicellularity, which is highly polyphyletic.
- Apoptosis is largely regulated by mitochondria
- there are two main theories for how the mitochondria endosymbioses started:
- parsitic hypothesis of mitochondrial endosymbioses: a parasitic option rather than cooperative
- hydrogen hypothesis: a cooperative option rather than parasitic
Smaller points:
- 10% of our body weight (dry presumably?) is mitochondria. Also quoted at: https://www.nature.com/scitable/blog/student-voices/mighty_mitochondria. TODO confirm.
- eukaryotes can do phatocytosis due to their cytoskeleton
- paints a colorful picture of Peter Mitchell. Some Wikipedia edits are warranted!
- it is hard for complex organisms to evolve because longer DNA means longer replication time
- cancer is natural selection gone wrong
- multicellular organisms are not utopias where every cell lives happily. Rather, they are dictatorships, where any dissident is forced to commit seppuku. Lu Xun's petition quote comes to mind.
Nitpicks:
- the book calls ATP synthase "ATPase" in several points, which is confusing because -ase means "something that breaks", and in 2020 parlance, there are ATPases which actually break ATP: https://en.wikipedia.org/wiki/ATPase. The book itself acknowledges that on page 135:
The ATPase is freely reversible. Under some circumstances it can go into reverse, whereupon it splits ATP, and uses the energy released to pump protons up the drive shaft, back across the membrane against the pressure of the reservoir. In fact the very name ATPase (rather than ATP synthase) signifies this action, which was discovered first. This bizarre trait hides a deep secret of life, and we’ll return to it in a moment.
Some criticisms:
- some of the later chapters are a bit more boring, like the stuff about warm-blooded animals. Perhaps is it that Ciro Santilli is more interested in the molecular aspects than macro
- the author talks about some very recent research at the time. While this does highlight his expertise, some of the points mentioned might still be in a state of flow. This is acknowledged by the author himself on the 2018 updated preface however.
Just like the adenine nucleotide translocator moves ATP/ADP in and out, this one moves loose phosphate in.
Both of those together recycle the cellular respiration carriers from/to the mitochondria.
Present in chormosome 4.
Good video showing what appears to be the adenine nucleotide translocator. although they don't use that name, instead saying ADP/ATP carrier.
The video also briefly depicts the ATP synthase and the mitochondrial phosphate carrier protein.
The key metabolic pathway of cellular respiration.
Happens in the matrix of the mitochondrion in eukaryotes.
Good animation explaining it: Video "Electron transport chain by HarvardX (2017)".
The fact that ATP is the universal energy storage mollecule of all life on Earth is such an incredible unifying principle of biology!
It is the direct output of all the major forms of "energy generation" in cells: ATP synthesis mechanism.
It is just as fundamental as the genetic code for example.
No wonder dozens of Nobel Prizes were related to its discovery, given its complexity.
ATP is the direct output of all the major forms of "energy generation" in cells:
One of the most beautiful molecular machines known!
The first one with such complexity that was uncovered.
The thing rotates like a water wheel for God's sake, except it uses protons instead of water.
The ATP synthase complex is so large that Power, Sex, Suicide by Nick Lane (2006) page 123 contains a cryoEM image of several ATP synthases on small membrane vesicles, this is the paper: https://pubs.acs.org/doi/abs/10.1021/bi00437a031# under a fucking paywall.
Both eukaryotic and prokaryotic ribosomes have a large and a small subunit.
The small one in comparison to the ribosome large subunit.
Organelle that is only present in prokaryotes.
Can either be a cell's dick used during bacterial conjugation, or little attachment anchors.
https://www.youtube.com/watch?v=-jIZ3bH-rAE "Illuminating biology at the nanoscale and systems scale using single-molecule and super-resolution imaging" by Xiaowei Zhuang (2017)
Ciro Santilli started taking some notes at: https://github.com/cirosantilli/awesome-whole-cell-simulation. but they are going to be all migrated here.
It is interesting to note how one talks about single cell analysis, in contrast to whole cell simulation: experimentally it is hard to analyse a single cell. But theoretically, it is hard to simulate a single cell. This mismatch is perhaps the ultimate frontier of molecular biology.