Discussions during our journal club.
October 22, 2024，第一、二章
2010s, ten big problems in physics, David Gross gene sequence → species drawing
DNA and ribosome, which came first? ribosome contains also RNA, which can self replicate…
DNA directly going to protein?
not right to call genes the blueprint, dynamics also sets up. rules and parts are clearly separated, but is it correct? In what case are they melted together.
nature vs. nurture
幂等生物系统？
老板作为老观点的卫道士，败于 bistability 和 chaos
“parallel to f=ma, here m contains information of f” (wouldn’t there be a fixed point after a few iterations?)
October 29, 2024 第三章
如果相信 Nick Lane 的观点，蛋白质酶是在金属离子催化剂进化，在周围修饰上蛋白质而产生的，这就意味着这个信息来自于环境（碱性热液喷口），而需要一种生物机制将信息刻录进生物分子，这种机制在哪里？
98% of genome is “junk”; 80% of nucleotide is transcribed. 没听清，不确定这两个说法。
Vintel: minimal requirements to build
E Coli have different fates, like stock phase and swimming phase
remove some ‘junk’ DNA:
This book was published 2023. There has been quite some advance in understanding gene activation.
Yeast genes are quite one next to another. But in other systems regulatory genes can be millions of base pairs away from the target gene.
How human genome sequence works given the hopping genes:
Transposons in yeasts are TN sequences
Insert transposons into strains of virus to mutate the virus at scale. TN-seq: https://www.nature.com/articles/nmeth.1377
Gene dosage being out of balance
“number of lncRNA without identifying biological functions is vanishingly small” said the boss with confidence.
conserved sequence should be functional.
Big population vs small population: probability of random neutral mutation will take up the population; in a small population this mutation with no evolution advantage still takes up.
epigenetics problem: there is no known mechanism that distinguishes 甲基化的 nucleotide from normal nucleotide during gene duplication, so how does it pass itself to the child
Organelle cloaking: pop-tag onto organelle membrane
November 12, 2024 Chapter 4
Anfinsen's Experiment: heating protein and cool down. Did they do it on one molecule or multiple? https://aklectures.com/lecture/structure-of-proteins/anfinsens-experiment-of-protein-folding
- Expose proteins with Urea and beta-mercaptoethanol, then remove both
- Remove one of them: lost bio-activity (could due to inter-cellular disulfide bonds)
- Add back a little bit of the removed one: back to nature structure
Turning a cooked egg back to raw?
I asked how we can know X ray structure is the biological active structure? Boss says cryo EM has lower resolution than X ray, but shows similar result.
Another way to think about this is to use NMR on live cells and examine the proteins.
“Alternative slicing” giving fuzzy functions
Motor proteins can be locked into various phases, and can give different diffraction patterns.
MINFLUX angstorms level optical images: https://www.nature.com/articles/s41467-021-21652-z
December 10, 2024 Chapter 5
Debate on how TF search their targets: 3d diffusion; first goes on DNA molecule, then search along the chain.
Experiments in bacteria was published to PRL (half and half); eukaryotic totally different.
galactose (GAL) network in yeasts
mycoplasma transplant/swaps experiment?
January 21, 2025 Chapter 6
Counter argument: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011288
cognition thing
neutralphillis chasing bacteria: LPS TLR4
in the cell fate decision, it’s legal to ask how far down the diagram a cell can go before there’s no way back.
cell function for single cell organisms? like during some transition in matabolism (glucose/galactose/raffinose) expression level 滞回线
scRNAseq data quality is BAD! dropouts, “imputations”?
the possible states of a cell is much more than the total number of cells, so cells only occupy a very small subspace of the whole space
scRNAseq data for all mouse cells: Mouse Cell Atlas: https://bis.zju.edu.cn/MCA/
February 4, 2025 Chapter 7
abnormality
See also: