New universe of miniproteins is upending cell biology and genetics • Hacker News Board

Re: New universe of miniproteins is upending cell biology and genetics

#51

Post by NeoBasilisk » Thu, Oct 17, 2019, 9:40 PM UTC

Dev_2019 wrote: post #17

ccvannorman wrote: post #5

* 'Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are,"…

We aren't curing aging any time soon are we :(?

Probably not soon enough to be of much benefit to anyone alive today. I have no qualifications to say this, so I can only base it on the staggering lack of progress made on many other medical fronts in the last decades.

Re: New universe of miniproteins is upending cell biology and genetics

#52

Post by dboreham » Thu, Oct 17, 2019, 9:42 PM UTC

dfsegoat wrote: post #16

danharaj wrote: post #7

Earlier quoted context omitted.

This is why you should be very skeptical of anyone who claims transparency between genetics and complex phenotypes.

Indeed. The whole "One Gene, One Protein [One Phenotype]" [1] dogma went out quite some time ago. ... But people and genetic testing companies seem to want to keep it going. [1] - https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-e...

We will eventually find that there's the equivalent of JPEG encoding (plus SSL and ECC) and that today we're doing the equivalent of someone with no knowledge of SSL or JPEG staring at a tcpdump trace of a browser loading an image over https, trying to make sense of the resulting hex dump.

Re: New universe of miniproteins is upending cell biology and genetics

#53

Post by OG_BME » Thu, Oct 17, 2019, 9:48 PM UTC

hprotagonist wrote: post #42

jdironman wrote: post #39

Earlier quoted context omitted.

We are just in the debugging phase.

i've been doing biological/biomedical research for about 20 years now (god, that's a scary thought...) I don't think that biology is well modeled by "being a meat computer", in general, but as far as the analogy goes ... : What we are debugging is 4.5 billion years of grad student code in at least a few dozen languages, with no documentation, method names that are outright lies, no separation of concerns at all, the…

Well said, I'm a biomedical engineer and even the cutting edge of research in this field is crushingly far from finding the capital T Truth of biology.

Re: New universe of miniproteins is upending cell biology and genetics

#54

Post by glenvdb » Thu, Oct 17, 2019, 9:57 PM UTC

gilleain wrote: post #47

newsocks wrote: post #21

How are miniproteins any different than just peptides? The article references "miniproteins"as being the same as "minipetides"... as though these are both different from regular peptides. Wikipedia states that peptides are "approximately 50 or fewer amino acids" [0] while minipeptides are "a length of less than 100-150 amino acids" [1]. Is this article really just saying that "peptides are upending cell biology"? [0]…

The boundary between 'peptide' and 'protein' is a little fuzzy. There are 'small proteins' like: https://en.m.wikipedia.org/wiki/Thionin that are 45-48 amino acids which is less than the (arbitrary) lower limit of 50. One distinguishing feature of a protein is that it folds, while peptides usually are too short to have a defined fold.

> while peptides usually are too short to have a defined fold.

That's not strictly true. My PhD project has looked at an entire class of peptides that are known to fold in to alpha-helices when bound to a cell membrane e.g. https://www.rcsb.org/structure/2k9b.

There are many others that are known to fold into beta-sheets too.

Re: New universe of miniproteins is upending cell biology and genetics

#55

Post by mvcalder » Thu, Oct 17, 2019, 10:04 PM UTC

paulsutter wrote: post #43

hprotagonist wrote: post #36

Earlier quoted context omitted.

fsvo "proof", i'm willing to take it as an axiom that biological systems are fractally weird in ways that are extremely resistant to formalism.

The patterns will be understood, by machines in whole and by people in part. To think it’s impossible seems ... religious

Huh,

From where I sit, to think it's possible seems ... religous. To each his own I guess.

Re: New universe of miniproteins is upending cell biology and genetics

#56

Post by drchewbacca » Thu, Oct 17, 2019, 10:05 PM UTC

Dev_2019 wrote: post #17

ccvannorman wrote: post #5

* 'Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are,"…

We aren't curing aging any time soon are we :(?

One nuance is that if you want to live forever you only need to hit longevity escape velocity where every year there is another discovery which buys you another year of healthy life.

Of course it might lead to living to 800 and being confined to a wheelchair by 80.

Re: New universe of miniproteins is upending cell biology and genetics

#57

Post by skissane » Thu, Oct 17, 2019, 10:09 PM UTC

Dev_2019 wrote: post #17

ccvannorman wrote: post #5

* 'Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are,"…

We aren't curing aging any time soon are we :(?

Define "curing". Is it giving some decent percentage of people an extra 10, 20, maybe even 30 years of reasonably healthy life, compared to what they have today? Or is it making people live forever? The first objective, as challenging as it is, sounds a lot more plausible than the second. If we ever achieve either, I'm sure the first will be reached long before the second is.

By a literal definition of "curing", only the second is a "cure". But the first would still be an amazing achievement, and is probably a prerequisite to ever being able to achieve the second.

Re: New universe of miniproteins is upending cell biology and genetics

#58

Post by stevenhuang » Thu, Oct 17, 2019, 10:09 PM UTC

mvcalder wrote: post #55

paulsutter wrote: post #43

Earlier quoted context omitted.

The patterns will be understood, by machines in whole and by people in part. To think it’s impossible seems ... religious

Huh, From where I sit, to think it's possible seems ... religous. To each his own I guess.

But to think it won't _ever_ be possible? After a thousand years of research?

Re: New universe of miniproteins is upending cell biology and genetics

#59

Post by 52-6F-62 » Thu, Oct 17, 2019, 10:17 PM UTC

hprotagonist wrote: post #42

jdironman wrote: post #39

Earlier quoted context omitted.

We are just in the debugging phase.

i've been doing biological/biomedical research for about 20 years now (god, that's a scary thought...) I don't think that biology is well modeled by "being a meat computer", in general, but as far as the analogy goes ... : What we are debugging is 4.5 billion years of grad student code in at least a few dozen languages, with no documentation, method names that are outright lies, no separation of concerns at all, the…

This literally made me laugh out loud. I’m glad I just got in before I read it. Well done, and I can only assume: well put.

Re: New universe of miniproteins is upending cell biology and genetics

#60

Post by gilleain » Thu, Oct 17, 2019, 10:17 PM UTC

glenvdb wrote: post #54

gilleain wrote: post #47

Earlier quoted context omitted.

The boundary between 'peptide' and 'protein' is a little fuzzy. There are 'small proteins' like: https://en.m.wikipedia.org/wiki/Thionin that are 45-48 amino acids which is less than the (arbitrary) lower limit of 50. One distinguishing feature of a protein is that it folds, while peptides usually are too short to have a defined fold.

> while peptides usually are too short to have a defined fold. That's not strictly true. My PhD project has looked at an entire class of peptides that are known to fold in to alpha-helices when bound to a cell membrane e.g. https://www.rcsb.org/structure/2k9b . There are many others that are known to fold into beta-sheets too.

Fair, but I would not really call a single helix a 'fold', either!

Ok, so I'm playing with definitions here a bit. Clearly 2k9b adopts a helical structure so it is 'folded' in some sense. However it has no tertiary structure.

Structural proteins like collagen are different again. They have a simple fold that could be described as quaternary (multichain), although that is again an abuse of terminology.

There are also some small proteins (peptides?) held together by disulphide links that have no secondary strucure to speak of. I think these are Class 4 in CATH, but I do not remember.

What is an example of a beta-sheet peptide? Amyloid is beta, I thought, but sheets are not normally stable outside sandwiches, barrels, etc