Month: November 2002

Minimal life

Craig Venter has been given ethical approval and a government grant to build the first artificial bacterium. He plans to create a single-celled organism with the minimum number of genes to sustain life.

This could be the drosophila of proteomics by having an idealized organism that is as simple as it can possibly be. Even then, this organism will still be orders of magnitude more complex than cellular automata. Now that I have more time, I need to delve into a new kind of science


2008-09-12: Syn3.0

J. Craig Venter’s work to build an artificial bacterium with the smallest number of genes necessary to live takes current life forms as a template. Protocell researchers are trying to design a completely novel form of life that may never have existed.

2014-09-03: See also this talk on synthetic life:

We now know we can create a synthetic organism. It’s not a question of ‘if’, or ‘how’, but ‘when‘, and in this regard, think weeks and months, not years.

2016-03-26: syn3.0 update:

Venter’s team painstakingly whittled down the genome of Mycoplasma mycoides to reveal a bare-bones set of genetic instructions capable of making life. syn3.0 contains just 473 genes or 531k bp, smaller than any independently replicating organism discovered on Earth to date. it is unclear what 149 of these genes do. also not a single gene is shared across all of life

2016-10-16: syn3.0 isn’t minimal though. Symbionts / parasites need ~50% DNA:

With only 160k base pairs of DNA, the genome of Carsonella ruddi is less than 50% the size thought to be the minimum necessary for life. Carsonella lives inside a leaf-munching insect, called a psyllid. They have a symbiotic relationship. The bacteria’s sheltered life has allowed it to pare its genome down to the bare minimum. There are certain genes necessary for life that the bacteria’s genome lacks, but these are compensated for by its insect host.

2022-02-25: And now some new work blends Alife with minimal life:

The minimal cell the team modeled, JCVI-syn3A, is an updated version of one presented in Science in 2016. Its genome is designed after that of the very simple bacterium Mycoplasmas mycoides, but stripped of genes that were not essential for life. JCVI-syn3A gets by with 493 genes, but no one knows what 94 of those genes do except that the cell dies without them. To build the new model, the team took an abundance of findings from various fields and wove them together. They used flash-frozen, thin-sliced images of the minimal cell to position its organic machinery precisely. A massive protein analysis helped them sprinkle all the right known proteins inside, and a detailed analysis of the cell membrane’s chemical composition helped them place molecules correctly on the outside. A thorough map of the cell’s biochemistry provided a rulebook for the interactions of the molecules.

As the digital cell grew and divided, 1000s of simulated biochemical reactions occurred, revealing how every molecule behaved and changed over time. The simulations mirrored many measurements of living JCVI-syn3A cells in culture. But they also predicted characteristics of the cells that hadn’t yet been noticed in the lab such as how the cell portions out its energy budget and how quickly its messenger RNA molecules degrade, a fact that critically affects researchers’ understanding of how the cell regulates genes. With a complete enough model, the researchers should be able to get creative: They can see what happens if they prune biochemical pathways, drop in extra molecules or set the simulation in a different environment. The results should give more insights into which processes cells need to survive — and which they don’t. They might even offer glimpses into what the very first cells required billions of years ago.


2022-02-28: New Yorker writeup: Richard Feynman once quipped that biology would be easy if you could “just look at the thing!” We are nearly there. “All these questions that people have. I think you’re going to be able to say, ‘Let’s just do a tomogram.’ ”

Some biologists are now combining approaches. Their goal is to create an integrated view of life inside the cell, in the form of a computer simulation that puts the whole system into motion. In grad school, Villa studied under Klaus Schulten, who helped develop the field of whole-cell computational modeling. Klaus worked from the bottom up, favoring “all-atom” simulations, in which virtual atoms follow the laws of quantum mechanics, while Zan worked from the top down, with “kinetic” models that track the cell’s larger traffic patterns. By the 2010s, the state of knowledge had advanced enough for them to try building a hybrid model. Klaus died in 2016. But, last month, Zan’s group published a paper in Cell that outlined a computational model of JCVI-syn3A. The model drew on cryo-EM images from Villa’s lab and on a genetic inventory supplied by J.C.V.I. It included all 452 of JCVI-syn3A’s proteins, plus other cellular bits. In the simulation, these parts interact among themselves as they would in real life.
The software aims to simulate a world that’s very different from ours. If a cell were blown up to the size of a high-school gym, you wouldn’t be able to see across it. It would be filled with 10000s of proteins, most about the size of a basketball. Other biomolecules no bigger than your hand, and water molecules the size of your thumb, would fill the spaces between. (To scale, your whole body would be about the size of a ribosome.) The mixture would have the consistency of hair gel. In such a world, gravity would be virtually meaningless—you would be weightless, as if suspended in a ball pit. And everything would be moving. The mixture would buzz constantly; spend just a few seconds inside it and every medium-sized object around you would have explored every square inch of your body. It would feel like pandemonium, but it wouldn’t be.

2022-03-13: More on cryo-ET and why it is such a big deal.

cryo-ET has evolved tremendously over the past 20 years. Advancements in the field will continue in the years to come, significantly enhancing our knowledge of prokaryotic cell biology. Those enhancements include but are not limited to improved sample preparation workflows, advances in hardware and software, and the curation of the vast amount of data into publicly available resources. Depending on the collection scheme and chosen magnification, fast tomography could increase collection time per target by 50–75%, vastly multiplying the amount of data that can be collected per sample. Resources such as the Caltech Electron Tomography Database have laid the groundwork for building comprehensive collections of cryo-ET data. In turn, some of this information has been translated into resources such the Atlas of Bacterial and Archaeal Cell Structure. This open access, digital resource provides detailed information about the prokaryotic ultrastructure of 85 species, which can be used as a source for comparison of structures in different strains, education, and comparison of sample treatments.

There’s also other microscopy techniques that have lower resolution, but can create 3D movies:

By combining 2 imaging technologies into Multimodal Optical System with Adaptive Imaging Correction (MOSAIC), scientists can now watch in unprecedented 3D detail as cancer cells crawl, spinal nerve circuits wire up, and immune cells cruise through a zebrafish’s inner ear.

2023-07-15: Regaining fitness

We went into the study thinking JCVI-syn3B simply wouldn’t be able to contend with the “inevitable mutations [that are] going to hit one of those essential genes”. The team pitted JCVI-syn3B against the first-generation JCV10syn1.0 from which it was derived. Each strain grew for 2k generations. Although both strains rapidly mutated, JCVI-syn3B could flexibly modify its genes like JCV10syn1.0, even though the latter had far more genetic letters to tolerate random mutations. Both bacterial strains survived similar types of genetic changes—insertions, deletions, and the switching of genetic letters—without a hitch.
“The initial effects of genome reduction were quite large; they made the cells sick”. Their fitness dropped by 50%. Fast-forward 2k generations, and it was a different picture. The minimal cells bounced back, regaining a fitness rate similar to their non-minimal cousins. Despite harboring a bare-boned genome, they readapted to their surroundings and overcame initial genetic shortfalls. The minimal cells’ main lifeline seemed to be “metabolic innovation.” Rather than adapting themselves to slurp more nutrients from the surrounding broth, the cells instead increased their ability to synthesize molecular pieces of fat into an outer protective layer, without sacrificing the lipid molecules essential for regeneration.

free.

i aced my last exam. i am now a master of computer science and business administration (for what its worth) the exam was totally awesome. i got to talk 45 minutes (30 minutes is the allotted time) about open source business models, culture, motivational issues, you name it. it was very interesting. so interesting in fact that my professor forgot to ask any questions relating to the subjects i was supposed to have studied. she was very eager to read my thesis, use it in her research, stay in touch. even offered me a phd position. WOHOO. do i rule or what. more later.

Peer production for information assets

i’m going to defend this paper by yochai benkler in a couple hours as part of my masters. benkler argues that there is a third mode of production besides markets and hierarchies (firms): peer production. per benkler, (and my own experience makes me agree with him) peer production is the most efficient mode of production for information because it reduces the opportunity costs of production that the other 2 models entail. markets are imprecise at valuing human resources because they have limited information, and hierarchies are inefficient at assigning tasks (also due to limited information). in the peer production model, individuals voluntarily flock to the tasks that interest them most, and where they can apply their skills most gainfully. it is asserted that individuals have the best available information about their skill set, and are thus much more efficient at task selection.

the internet enables a unbounded pool of human resources to seek out problems. these economies of scale easily overcome the additional costs of integration and coordination in a highly distributed environment. with proper attribution and meritocratic structures, problems of burn-out and free riding can be overcome.

it should be an interesting discussion, especially considering that the relevant institute has been conducting research into the open source phenomenon recently.

proustian qualities

Clearly there is a higher purpose to these discursive ruminations. In describing in great detail the new dog his next-door neighbor just got or by writing about how he was tired and just drank 3 cups of coffee from the vending machine down the hall, Eric is seeking to rescue these moments from the clutches of the past. Proust had the same obsession with the inexorable passage of time. I really have to hand it to Eric, how he elevates the importance of certain events in his life while simultaneously revealing their essential hollowness.

reading some blogs, you can totally find this quality. whether it adds value to the global discourse besides being an outlet for the blogging person, who knows. more reflection and less sup, dude? might lift quite a few of them above the irrelevance threshold.

principles

i found these, and liked them sufficiently enough to merit a post.

The Libertarian Party’s Statement of Principles

We, the members of the Libertarian Party, challenge the cult of the omnipotent state and defend the rights of the individual.

We hold that all individuals have the right to exercise sole dominion over their own lives, and have the right to live in whatever manner they choose, so long as they do not forcibly interfere with the equal right of others to live in whatever manner they choose.

Governments throughout history have regularly operated on the opposite principle, that the State has the right to dispose of the lives of individuals and the fruits of their labor. All political parties other than our own grant to government the right to regulate the lives of individuals and seize the fruits of their labor without their consent.

We, on the contrary, deny the right of any government to do these things, and hold that where governments exist, they must not violate the rights of any individual: namely, (1) the right to life — we support the prohibition of the initiation of physical force against others; (2) the right to liberty of speech and action — we oppose all attempts by government to abridge the freedom of speech and press, as well as government censorship in any form; and (3) the right to property — we oppose all government interference with private property, such as confiscation, nationalization, and eminent domain, and support the prohibition of robbery, trespass, fraud, and misrepresentation.

Since governments, when instituted, must not violate individual rights, we oppose all interference by government in the areas of voluntary and contractual relations among individuals. People should not be forced to sacrifice their lives and property for the benefit of others. They should be left free by government to deal with one another as free traders; and the resultant economic system, the only one compatible with the protection of individual rights, is the free market.

Brainpower

So a computer with the processing capacity of a human brain is to be put to work by the government? Does the US government have any actual experience in managing something as powerful as a human brain? How long before the computer realizes it could do much better in the private sector?

Portents

I tried to install my machine at my new employer today. After 1 hour, the network card stopped working. I decided to call it a day and went home. This is just the most recent episode in a long string of computer incidents that happen to me. Maybe i’m in the wrong trade.