4 ms·

Really fascinating! I wonder if these cells all have defects in innate immune sensing of cytosolic DNA. Like, do cGAS/MAPK/etc. require linear for recognition l

Really fascinating! I wonder if these cells all have defects in innate immune sensing of cytosolic DNA. Like, do cGAS/MAPK/etc. require linear for recognition like RIG-I does for dsRNA or are they all mutated/shutdown in these cells. Would be interesting to see the innate immune transcriptome with and without ecDNA.

panabee 5y ago
one of the best accelerants for science would be empowering non-researchers like you to hire researchers to conduct experiments like this -- or ideally conduct experiments yourself. equipment, material, and people costs are prohibitively high for now. hopefully one day.
- ncmncm 5y ago
  Ideas are cheap. Every biologist has way more ideas for what to investigate than they could ever get grants to look into. Grant committees, likewise, see applications for way more research programs than they have money to fund. (This is like startup ideas, founders, and VCs.) But grant committees are controlled by the older members of each sub-field. They are biased toward what seemed important to them when they were young, but also against what experience has taught them tend to be dead ends. They want questions explored that have gone wanting for decades. Young researchers will eventually graduate to grant committees, and fund what they wish had been looked into decades before. We can see systematic failure in, e.g., Alzheimer syndrome research, still funding suppression of amyloid plaques and tau tangles decades after every such avenue was found to fizzle. But we don't know a better way to organize evaluating grant applications. We would not know how to evaluate any change proposed. And, we don't know how to change committees over if we found a better one. Each sub-field has its own dynamic, independent of all the others. Probably some have evolved a method that works well for their sub-field, for now, but would certainly be wrong for the next sub-field over, and will be wrong in its own in ten years. They are all playing catch-up all the time. The only thing that keeps it working at all is that they are run by smart people who have had to solve many different hard problems, and those people retire on a regular schedule.
  - panabee 5y ago
    agreed. however, lowering barriers so more people can help also means potentially clearing the idea backlog faster. the startup analogy is right: sometimes a promising idea requires another implementation (experiment in this case) for validation/invalidation. similar to ecDNAs, novobiocin, and other cases. science funding is indeed broken. only 7% of NIH grants go to researchers under 40. tesla, apple, and many impactful companies were started by founders under 40. watson, crick, and currie were all under 40 when making seminal contributions to science. imagine how many breakthrough ideas are gated in science right now. the NIH is amazing but not allowed to take risk: how can we fund more unestablished scientists?
    - DrAwdeOccarim 5y ago
      industry. i'll just say it plainly. that's where you can fund more unestablished scientists. the vc world, the smart ones, are now funding moonshot ideas from younger scientists in ways academic science funding methods will never match. if you're a young scientist with crazy ideas, try to hitch up with vc's that run an incubator. the first step, though, is to move to boston.
- DrAwdeOccarim 5y ago
  i appreciate the vote of confidence! to assuage your concerns, i'm part of the research planning team at a major biopharma. so funding, executing, and analyzing these kinds of experiments is my day job : )
  - panabee 5y ago
    in the same way FAANG engineers build impactful projects on the side, it would only help science if we could empower talented people like you to conduct your own "side" experiments. let's hope the day comes soon.
    - DrAwdeOccarim 5y ago
      it boils down to costs. spinning up some code on your laptop is effectively free. of course your time, electricity, laptop depreciating, etc. cost money, but it's negligible if you're just taking a break from earning your living in that space. to execute a biological experiment, you need to move liquids around which adds a ton of costs for handling said liquids. also, you need to indirectly analyze the results, which requires equipment to amplify/change the output to a human readable format. i've returned to issac asimov's response to innovation: find the smartest people, pay them a stipend contingent on completing some quick menial task, and then leave them be for a few weeks. out the other end you'll have innovations.
      - panabee 5y ago
        this is right. driving down costs is crucial in science (and other fields actually). as software grows more sophisticated, this will happen. startups like https://mbcbiolabs.com https://mbcbiolabs.com are starting to lower lab costs, and this trend will only accelerate over time. what are your favorite resources/labs for tracking research?

panabee 5y ago

one of the best accelerants for science would be empowering non-researchers like you to hire researchers to conduct experiments like this -- or ideally conduct experiments yourself. equipment, material, and people costs are prohibitively high for now. hopefully one day.

ncmncm 5y ago
Ideas are cheap. Every biologist has way more ideas for what to investigate than they could ever get grants to look into. Grant committees, likewise, see applications for way more research programs than they have money to fund. (This is like startup ideas, founders, and VCs.) But grant committees are controlled by the older members of each sub-field. They are biased toward what seemed important to them when they were young, but also against what experience has taught them tend to be dead ends. They want questions explored that have gone wanting for decades. Young researchers will eventually graduate to grant committees, and fund what they wish had been looked into decades before. We can see systematic failure in, e.g., Alzheimer syndrome research, still funding suppression of amyloid plaques and tau tangles decades after every such avenue was found to fizzle. But we don't know a better way to organize evaluating grant applications. We would not know how to evaluate any change proposed. And, we don't know how to change committees over if we found a better one. Each sub-field has its own dynamic, independent of all the others. Probably some have evolved a method that works well for their sub-field, for now, but would certainly be wrong for the next sub-field over, and will be wrong in its own in ten years. They are all playing catch-up all the time. The only thing that keeps it working at all is that they are run by smart people who have had to solve many different hard problems, and those people retire on a regular schedule.
- panabee 5y ago
  agreed. however, lowering barriers so more people can help also means potentially clearing the idea backlog faster. the startup analogy is right: sometimes a promising idea requires another implementation (experiment in this case) for validation/invalidation. similar to ecDNAs, novobiocin, and other cases. science funding is indeed broken. only 7% of NIH grants go to researchers under 40. tesla, apple, and many impactful companies were started by founders under 40. watson, crick, and currie were all under 40 when making seminal contributions to science. imagine how many breakthrough ideas are gated in science right now. the NIH is amazing but not allowed to take risk: how can we fund more unestablished scientists?
  - DrAwdeOccarim 5y ago
    industry. i'll just say it plainly. that's where you can fund more unestablished scientists. the vc world, the smart ones, are now funding moonshot ideas from younger scientists in ways academic science funding methods will never match. if you're a young scientist with crazy ideas, try to hitch up with vc's that run an incubator. the first step, though, is to move to boston.
DrAwdeOccarim 5y ago
i appreciate the vote of confidence! to assuage your concerns, i'm part of the research planning team at a major biopharma. so funding, executing, and analyzing these kinds of experiments is my day job : )
- panabee 5y ago
  in the same way FAANG engineers build impactful projects on the side, it would only help science if we could empower talented people like you to conduct your own "side" experiments. let's hope the day comes soon.
  - DrAwdeOccarim 5y ago
    it boils down to costs. spinning up some code on your laptop is effectively free. of course your time, electricity, laptop depreciating, etc. cost money, but it's negligible if you're just taking a break from earning your living in that space. to execute a biological experiment, you need to move liquids around which adds a ton of costs for handling said liquids. also, you need to indirectly analyze the results, which requires equipment to amplify/change the output to a human readable format. i've returned to issac asimov's response to innovation: find the smartest people, pay them a stipend contingent on completing some quick menial task, and then leave them be for a few weeks. out the other end you'll have innovations.
    - panabee 5y ago
      this is right. driving down costs is crucial in science (and other fields actually). as software grows more sophisticated, this will happen. startups like https://mbcbiolabs.com https://mbcbiolabs.com are starting to lower lab costs, and this trend will only accelerate over time. what are your favorite resources/labs for tracking research?