From a quick skim: what's interesting about this study from an HN perspective is that they used Alphafold (or more specifically Alphafold-Multimer: https://www.biorxiv.org/content/10.1101/2021.10.04.463034v2....) to screen more than 1400 different proteins that were likely to be present on zebrafish sperm to see which ones might bind to other known sperm fertility factors.
Lo, and behold, they found a protein (i.e, the product of a particular zebrafish gene) that Alphafold-Multimer predicted would bind to two of the known sperm factors. And it turned out to be a kind of missing link: the three sperm proteins together were predicted form a stable structure. And, that structure ("complex") sticks to the only egg protein known to be required for fertilization! (Where all of this was first predicted using Alphafold-Multimer, then experimentally confirmed to some degree.)
Not only that, it turns out human versions ("orthologs") of these three sperm proteins exist, and their experimental evidence at least suggests that they stick together, forming a complex as well. Which presumably sticks to some human egg protein. Pretty neat.
Why this matters: Consider. 20 years ago, I briefly worked for a lab that used genetics to study fertilization in C. elegans (fast breeding, millimeter-long worms with a lot of infrastructure in place for scientific study). Sure, we were studying worms, but the PI had a personal interest in (in)fertility, and it was his long bet that fundamental research would help medicine solve infertility.
Now it looks like the bet is showing promise of paying off: back then, there didn't seem to be any vertebrate equivalents of the worm genes we found. Maybe worm fertilization was just too far removed. But the top "related article" is from my old lab (https://www.cell.com/current-biology/fulltext/S0960-9822(23)...) and the abstract points out that several worm genes they and related labs found are, in fact, equivalents of the vertebrate genes discussed in TFA! So progress accelerates.
What are other important “protein complexes” that we know of in biology? Seems like they may have relevance as an important precursor in the pathway of the evolution of life
Next step, design a drug to block it, and we have a new contraceptive that doesn't involve throwing a spanner in the works of anyone's endocrine system.
The animation illustrating the AlphaFold-predicted structural models of the trimeric sperm complex in zebrafish, mice and humans shows shocking similarity.
I remember Richard Dawkins talking about the "male fertility crisis" some years ago, and how little we still truly knew about it. Maybe this can shed some light.
It's "just" a model, but I wouldn't be at all surprised that there is biological machinery reused across all sexually-reproducing species, since sex evolved billions of years ago and there's nothing very exceptional about the human implementation of it.
I think you've drawn the wrong conclusion. Just because a life has a step early in the process of forming that includes an egg and a sperm does not mean that it is a living thing at that point. You are affirming the consequent here, which is a logical fallacy.
The original goal of the university was to bring together knowledge from disparate disciplines. It was believed that knowledge in the fullest sense would be attained via achieving a unity of knowledge across diverse disciplines.
Hence the term "university" which comes from the words "unity" and "diversity". Every academic discipline has something to contribute - and a fully formed mind does best to draw from and be informed by multiple contexts at once.
If two academic disciplines or contexts contradict one another, we ought to take that as an indication of an underlying problem somewhere. In this case, the paper's authors seem not to have gotten the memo. Perhaps a simple acknowledgment of agreement with orthodoxy would suffice - otherwise the opening sentence might cause misinformation. As it is, hopefully it doesn't accidentally get quoted without sufficient clarification by the media.
They don't contradict each other, the contexts are different. Words have subtly different meanings according to what is being discussed. English is not a context-free language.
Contexts ought to be able to overlap and inform each other without direct contradictions -- otherwise, there's (at minimum) a lack of logical validity and hence untruth somewhere.
The words we use (and their meanings) matter, because they are the substrate with which we think and act.
Any way to bring that up without logging into a Google account?
I hate how many products have become login-walled gardens (eg. Twitter, Instagram, various forums and newsites that render differently to crawlers than to me, etc...)
From a quick skim: what's interesting about this study from an HN perspective is that they used Alphafold (or more specifically Alphafold-Multimer: https://www.biorxiv.org/content/10.1101/2021.10.04.463034v2....) to screen more than 1400 different proteins that were likely to be present on zebrafish sperm to see which ones might bind to other known sperm fertility factors.
Lo, and behold, they found a protein (i.e, the product of a particular zebrafish gene) that Alphafold-Multimer predicted would bind to two of the known sperm factors. And it turned out to be a kind of missing link: the three sperm proteins together were predicted form a stable structure. And, that structure ("complex") sticks to the only egg protein known to be required for fertilization! (Where all of this was first predicted using Alphafold-Multimer, then experimentally confirmed to some degree.)
Not only that, it turns out human versions ("orthologs") of these three sperm proteins exist, and their experimental evidence at least suggests that they stick together, forming a complex as well. Which presumably sticks to some human egg protein. Pretty neat.
Why this matters: Consider. 20 years ago, I briefly worked for a lab that used genetics to study fertilization in C. elegans (fast breeding, millimeter-long worms with a lot of infrastructure in place for scientific study). Sure, we were studying worms, but the PI had a personal interest in (in)fertility, and it was his long bet that fundamental research would help medicine solve infertility.
Now it looks like the bet is showing promise of paying off: back then, there didn't seem to be any vertebrate equivalents of the worm genes we found. Maybe worm fertilization was just too far removed. But the top "related article" is from my old lab (https://www.cell.com/current-biology/fulltext/S0960-9822(23)...) and the abstract points out that several worm genes they and related labs found are, in fact, equivalents of the vertebrate genes discussed in TFA! So progress accelerates.
What are other important “protein complexes” that we know of in biology? Seems like they may have relevance as an important precursor in the pathway of the evolution of life
Far too many to list here, but some interesting ones re the evolution of life might be the complexes responsible for transcription of genes and translation into proteins, such https://en.wikipedia.org/wiki/DNA_polymerase_III_holoenzyme, RNA polymerase (https://en.wikipedia.org/wiki/RNA_polymerase), and the ribosome (https://en.wikipedia.org/wiki/Ribosome).
Start your journey here: https://archive.org/details/alberts-molecular-biology-of-the...
Next step, design a drug to block it, and we have a new contraceptive that doesn't involve throwing a spanner in the works of anyone's endocrine system.
Worse, vaccinate against it or write a virus to express analogue structures during intracellular construction, and you might have Children of Men.
Also: "Childhood's End"
https://s3.us-west-1.wasabisys.com/luminist/EB/C/Clarke%20-%...
The animation illustrating the AlphaFold-predicted structural models of the trimeric sperm complex in zebrafish, mice and humans shows shocking similarity.
I remember Richard Dawkins talking about the "male fertility crisis" some years ago, and how little we still truly knew about it. Maybe this can shed some light.
It's "just" a model, but I wouldn't be at all surprised that there is biological machinery reused across all sexually-reproducing species, since sex evolved billions of years ago and there's nothing very exceptional about the human implementation of it.
I’ve never stumbled so much through a title….
COMplex (noun) as opposed to comPLEX (adj) might help you
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I think you've drawn the wrong conclusion. Just because a life has a step early in the process of forming that includes an egg and a sperm does not mean that it is a living thing at that point. You are affirming the consequent here, which is a logical fallacy.
I was pointing out the inconsistency of the opening statement with modern orthodoxy, not presenting a logical argument either way.
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I think these are definitions from very different contexts.
The original goal of the university was to bring together knowledge from disparate disciplines. It was believed that knowledge in the fullest sense would be attained via achieving a unity of knowledge across diverse disciplines.
Hence the term "university" which comes from the words "unity" and "diversity". Every academic discipline has something to contribute - and a fully formed mind does best to draw from and be informed by multiple contexts at once.
If two academic disciplines or contexts contradict one another, we ought to take that as an indication of an underlying problem somewhere. In this case, the paper's authors seem not to have gotten the memo. Perhaps a simple acknowledgment of agreement with orthodoxy would suffice - otherwise the opening sentence might cause misinformation. As it is, hopefully it doesn't accidentally get quoted without sufficient clarification by the media.
They don't contradict each other, the contexts are different. Words have subtly different meanings according to what is being discussed. English is not a context-free language.
Contexts ought to be able to overlap and inform each other without direct contradictions -- otherwise, there's (at minimum) a lack of logical validity and hence untruth somewhere.
The words we use (and their meanings) matter, because they are the substrate with which we think and act.
[flagged]
Any way to bring that up without logging into a Google account?
I hate how many products have become login-walled gardens (eg. Twitter, Instagram, various forums and newsites that render differently to crawlers than to me, etc...)
Doesn't matter if what the LLM says isn't factually true as long as we're all too ignorant to tell!