ababaian
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Comment · 1 year ago
Comment · 1 year ago
The Laboratory for RNA-Based Lifeforms | University of Toronto | Full-Time | ONSITE | RNAlab.ca
Howdy, The Laboratory of RNA-Based Lifeforms based out of UofT is looking for post-doctoral fellows, independent researchers, and/or a cloud engineer. We're a research computational biology lab at the forefront of massive scale genetics analysis (think petabytes). We have two ongoing projects: (1) Serratus focuses on the discovery of novel RNA viruses and RNA infectious agents. Currently we're focusing on identifying cancer-causing viruses in humans. By identifying these viruses, we can develop treatments for them. (2) PlastiDB is a new project where we are searching for enzymes which are capable of bio-remediating microplastics. By reducing microplastics in our environment, we're building a cleaner world for the future.
Seeking a full-stack developer who is creative, passionate, and willing to learn. No biology experience is necessary, but it's an asset. Key skills: Python/R, AWS/HPC, postgres, Neo4j/graph databases, javascript. See full job posting on https://www.rnalab.ca/join
Select Media:
* Hacker News Post about Obelisk RNA elements (Cell Paper): https://news.ycombinator.com/item?id=42547489
* Serratus (Nature Paper): https://www.nature.com/articles/s41586-021-04332-2
* CBC News Story: https://www.cbc.ca/news/health/supercomputer-virus-study-dis...
* Gairdner Lecture: https://www.youtube.com/watch?v=mPUM-adhXd8&t=5875
Comment · 1 year ago
Not sure I understand. Obelisks seems an inert descriptor to me, it has no connotation in the field so it's appropriately a blank slate.
Comment · 1 year ago
How would they exist/maintain themselves without it's DNA counterpart?
Comment · 1 year ago
Vanya thought that when you run them through the RNA folding software, it would give you these unusual straight rods which reminded him of Cleopatra's Needle (Obelisk, https://en.wikipedia.org/wiki/Cleopatra%27s_Needles). The name stuck around. Incidentally the name has some cool 2001: Space Odyssey monolith vibes to it, which I think has been fitting.
Comment · 1 year ago
Absolutely, reading Selfish Gene in high school set me on the path to this type of exploration. Genes, in the pure abstract sense, are the unit by which we interrogate understand evolutionary change. There's a large grey area about the boundaries of genes, but after a certain point, genes assemble into operational units larger than themselves, a genome. Obelisks are some of the simplest, most rudimentary genomes described thus far.
Comment · 1 year ago
I like to view it that we're all RNA-based lifeforms. Operationally: DNA, RNA, or other are just a vehicles which hold our information.
This podcast RadioLab with Carl Zimmer (11m) I think captures the essence of the idea near perfectly: https://radiolab.org/podcast/creation-translation
Comment · 1 year ago
That's exactly what they are though, some piece of garbage RNA cells are producing. A lot of things meet that definition if you think about it.
Comment · 1 year ago
It's not OT at all. It depends on what you mean exactly by LLM, but we use them all the time. ESMFold2 was an LLM [https://www.science.org/doi/10.1126/science.ade2574] and was instrumental in advancing deep protein fold prediction in metagenomic space. Likewise AlphaFold2 it's direct application in creating FoldSeek for ultra-deep homology search. Both of these actually have radically improved our capacity to say Obelisks are _REALLY_ not like anything that's known.
Besides that I encourage all students to use ChatGPT for research, coding, copy editing, etc... I haven't encountered an LLM that can deal with difficult domain problems like we're facing, but I'd welcome the help. I'm for using all tools available, my main criticism with AI/LLM in general is the poor way in which uncertainty is reported.
Comment · 1 year ago
The classic phylogenetic classes are a fantastic model, but https://en.wikipedia.org/wiki/All_models_are_wrong :)
Phylogeny is the study by which things relate to one another. There is a divergence point at which point it becomes impossible to relate two sequences to one another. Obelisks, Zeta-Elements, Deltaviruses, viroids all veer towards their own divergence point into infinity, but their are higher-order genome organization traits which are consistent. We don't know if these traits are the same by origin, or the same by chance. Interestingly Ambiviruses also have this genome organization, but they have a protein which is de facto of an RNA virus.
My opinion is that these simple genome layouts (structured circular RNA elements with ribozymes) are like a cauldron of mixing simple genes, and when they come together just the right way, we see those lineages take off. Think of it as an ocean of ancient primordial RNA replicators, ready to fire off, and this process is ongoing even today.
Comment · 1 year ago
These are two distinct questions. Are Obelisks part of the self? If you think of the "host" as being made up by it's DNA, then these are not part of that set, since they are not found in DNA copies. Or is an organism it's RNA? If it's the RNA that's the organism, then sure you could say this is part of that organism in that it exist as organelles of sorts, like mitochondria or chloroplasts (but in RNA form).
The second question is if it's parasitic, mutualistic, or neutral. If it's a parasite it should cause a fitness defect to the DNA organism's replication. As of yet I haven't seen evidence of this at the cellular level. But there is a strong argument that by depleting cells of nucleic acids (RNA) would have to be at least minimally parasitic. That is of course unless they confer some advantage to the cells with Obelisks. In which case, why don't all microbial cells have Obelisks. Importantly, the relationships between all the various Obelisks at least for now, is not lining up with microbial genome evolution. This would mean they are jumping from genome to genome.
Now you're in a late night pub discussion about where we should be drawing the boundaries of life.
Comment · 1 year ago
We certainly have the data, too much so actually. I should correct the statement to say, we have insufficiently developed _applied_ information theory.
We know how to quantify homology, it just has not been applied to sufficient depth to the field of RNA/viroid evolution to resolve how much of an RNA element with extensive secondary structure, or ribozyme is evidence of a homology vs. convergence. And how could we resolve the two? It's easy with protein sequences, tricky with protein structures, but deep RNA evolution? That's a mystery.
Comment · 1 year ago
What have Obelisks ever done to you? Our first reaction shouldn't be to kill everything we don't understand :'(
Good pragmatic question though. It's not clear if any drugs up- or down-regulate Obelisk genome copy, you could re-investigate other drug-treatment studies to see if Obelisks incidentally present are altered and get an "accidental" study.
From a molecular perspective, the most likely compounds and methods would be those which work against viroid replication (i.e. RNA polymerase inhibitors, translational inhibitors, CRISPR,...). You just have to maintain a preferential toxicity to Obelisks over host cells.
Comment · 1 year ago
If you want the real mind-trip, try to think about how little we know about detecting "life" that is not based on nucleic acids.
Comment · 1 year ago
Not that I know of, although this doesn't mean it isn't happening, it's something which has to be investigated in detail.
We’re engineering enzymes to degrade microplastics using AI + high-throughput molecular biology. Join the Laboratory for RNA-Based Lifeforms (https://RNAlab.ca | PI: Artem Babaian) on one of the largest projects in bioinformatics today. Building on Serratus (10× RNA virus discovery, Nature 2022), we’re now developing Logan to mine planetary-scale genomics datasets to evolve and test novel plastic-degrading enzymes.
Looking for: * PhD in Molecular/Synthetic Biology, Biochemistry, or Genetics
* Strong skills in yeast/bacterial systems, enzyme assays, or metabolic engineering
* Interest in automation, robotics, and collaboration with AI and Computational Biology scientists
Full-time postdoc in Toronto, Canada. Start date: flexible/immediate.
Apply Today: https://jobrxiv.org/job/university-of-toronto-27778-syntheti...
----- Relevant Links:
* Serratus paper (https://www.nature.com/articles/s41586-021-04332-2)
* Logan preprint (https://www.biorxiv.org/content/10.1101/2024.07.30.605881v2)
* Entering The Platinum Age of Computational Discovery. Vision. (10m; https://www.youtube.com/watch?v=mPUM-adhXd8&t=5875s)
Let’s build the biology together to clean Our Planet.